WorldWideScience

Sample records for cancer chemopreventive agents

  1. Aspirin as a Chemopreventive Agent for Cancer: a New Hope?

    Directory of Open Access Journals (Sweden)

    Isnatin Miladiyah

    2016-01-01

    Full Text Available Introduction: inflammation has been shown to play a major role in the pathogenesis of cancer. Inflammatory process activates the immune system through pro-inflammatory mediators and subsequent triggers transformation into malignant cells. Some tumors or cancers has been associated with chronic infections, such as hepatitis B and C viruses (hepatocellular carcinoma, human papilloma virus (cervical cancer, Helicobacter pylori (gastric cancer and lymphoma, and prostatitis (prostate cancer. A considerable study have investigated the benefits of aspirin for the prevention and treatment of cancer or tumors. Objectives: This paper aims to describe the relationship between inflammation and cancer incidence, so that use of aspirin as an anti-inflammatory agent is a rational choice in the treatment and prevention of cancer. Conclusion: Aspirin potential for chemoprevention of various types of cancer. Considering the high risk of side effects of aspirin, aspirin is not intended as a routine therapy to prevent the occurrence of cancer.

  2. Flavonoids, Breast Cancer Chemopreventive and/or Chemotherapeutic Agents.

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    Magne Nde, Chantal Beatrice; Zingue, Stephane; Winter, Evelyn; Creczynski-Pasa, Tânia Beatriz; Michel, Thomas; Fernandez, Xavier; Njamen, Dieudonne; Clyne, Colin

    2015-01-01

    Flavonoids are secondary metabolites abundantly present in commonly consumed fruits and vegetables. They possess diverse properties such as anti-inflammatory, anti-oxidant and anti-cancer. Epidemiologic studies suggest that an enrich flavonoids diet is linked to a decreased risk of breast cancer. These protective properties are due to the alteration of numerous signalling pathways involved in cancer-related phenomena such as inflammation and proliferation. Human clinical trials examining the effect of supplementation of some flavonoids on disease prevention have been conducted. There is no natural flavonoid that has been approved for the treatment of breast cancer. However, natural flavonoids served as lead compounds in the synthesis of cancer chemopreventive and/or therapeutic agents.

  3. Cancer chemopreventive agents, 4-phenylcoumarins from Calophyllum inophyllum.

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    Itoigawa, M; Ito, C; Tan, H T; Kuchide, M; Tokuda, H; Nishino, H; Furukawa, H

    2001-08-10

    In a search for anti-tumor-promoting agents, we carried out a primary screening of ten 4-phenylcoumarins isolated from Calophyllum inophyllum L. (Guttiferae), by examining their possible inhibitory effects on Epstein--Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. All of the compounds tested in this study showed inhibitory activity against EBV, without showing any cytotoxicity. Calocoumarin-A (5) showed more potent activity than any of the other compounds tested. Furthermore, calocoumarin-A (5) exhibited a marked inhibitory effect on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. The results of the present investigation indicate that some of these 4-phenylcoumarins might be valuable as potential cancer chemopreventive agents (anti-tumor-promoters).

  4. Aspirin as a chemoprevention agent for colorectal cancer.

    LENUS (Irish Health Repository)

    Lee, Chun Seng

    2012-11-01

    Colorectal cancer (CRC) is one of the leading causes of mortality in the western world. It is widely accepted that neoplasms such as colonic polyps are precursors to CRC formation; with the polyp-adenoma-carcinoma sequences well described in medical literature [1, 2]. It has been shown that Aspirin and other non-steroid anti-inflammatory drugs (NSAID) have a negative effect on polyp and cancer formation. This review aims to describe some of the mechanism behind the chemoprotective properties of aspirin; COX 2 inhibition, regulation of proliferation and apoptosis and effects on the immune system and also the current evidence that supports its use as a chemoprevention agent against CRC. We will also aim to explore the side effects with the use of aspirin and the pitfalls of using aspirin routinely for primary prophylaxis against CRC.

  5. Neoflavonoids and tetrahydroquinolones as possible cancer chemopreventive agents

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    Luqman, Suaib; Meena, Abha; Singh, Pragya; Kondratyuk, Tamara P.; Marler, Laura E.; Pezzuto, John M.; Negi, Arvind Singh

    2012-01-01

    Several lactone and lactam based neoflavonoids and tetrahydroquinolones were synthesized and evaluated for cancer chemopreventive studies using cell and molecular target based in vitro bioassays, namely NFκB, aromatase, and quinone reductase 1 (QR1). These analogues blocked TNF-α-induced NFκB activation in a dose-dependent manner with IC50 values in the range of 0.11–3.2 μM. In addition, compound 8 inhibited aromatase activity with an IC50 value of 12.12 μM and compound 10 affected QR1 induction (IR: 3.6, CD: 19.57 μM). Neoflavonoids 8 and 10 exhibiting good results, can further be optimized for improved therapeutic profiles. However, investigations into the actions of neoflavonoids and tetrahydroquinolones, especially those related to the NFκB signaling pathway, aromatase inhibition, induction of QR1 expression and in vivo studies could provide new insights into the cancer chemopreventive ability of these molecules. PMID:22726671

  6. ent-Rosane and abietane diterpenoids as cancer chemopreventive agents.

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    Núñez, Marvin J; Reyes, Carolina P; Jiménez, Ignacio A; Hayashi, Hirotaka; Tokuda, Harukuni; Bazzocchi, Isabel L

    2011-04-01

    Two ent-rosane- (cuzcol, 1 and 6-dehydroxycuzcol, 2) and a abietatriene- (salvadoriol, 3) type diterpenoids have been isolated from Maytenus cuzcoina and Crossopetalum uragoga, respectively, along with five known diterpene compounds (4-8). Their stereostructures have been elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR techniques, and computational data. The absolute configuration of cuzcol was determined by application of Riguera ester procedure. This is the first instance of isolation of ent-rosane diterpenoids from species of the Celastraceae. The isolated diterpenes were found to be potent anti-tumour-promoter agents, and carnosol (7) also showed a remarkable chemopreventive effect in an in vivo two-stage carcinogenesis model. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Plant Polyphenols as Chemopreventive Agents for Lung Cancer

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    Madumani Amararathna

    2016-08-01

    Full Text Available Lung cancer may be prevented by a diet rich in fruits and vegetables as they are enriched with dietary antioxidant polyphenols, such as flavonoids, proanthocyanidins, lignans, stilbenes, and phenolic acids. Dietary polyphenols exert a wide range of beneficial biological functions beyond their antioxidative properties and are involved in regulation of cell survival pathways leading to anticarcinogenic and antimutagenic functions. There are sufficient evidence from in vitro, in vivo, and epidemiological studies to suggest that the dietary intervention of polyphenols in cancer prevention, including the chemopreventive ability of dietary polyphenols, act against lung carcinogens. Cohort and epidemiological studies in selected risk populations have evaluated clinical effects of polyphenols. Polyphenols have demonstrated three major actions: antioxidative activity, regulation of phase I and II enzymes, and regulation of cell survival pathways against lung carcinogenesis. They have also shown an inverse association of lung cancer occurrences among high risk populations who consumed considerable amounts of fruits and vegetables in their daily diet. In in vitro cell culture experimental models, polyphenols bind with electrophilic metabolites from carcinogens, inactivate cellular oxygen radicals, prevent membrane lipid peroxidation and DNA oxidative damage, and adduct formation. Further, polyphenols enhance the detoxifying enzymes such as the phase II enzymes, glutathione transferases and glucuronosyl transferases.

  8. Plant Polyphenols as Chemopreventive Agents for Lung Cancer.

    Science.gov (United States)

    Amararathna, Madumani; Johnston, Michael R; Rupasinghe, H P Vasantha

    2016-08-19

    Lung cancer may be prevented by a diet rich in fruits and vegetables as they are enriched with dietary antioxidant polyphenols, such as flavonoids, proanthocyanidins, lignans, stilbenes, and phenolic acids. Dietary polyphenols exert a wide range of beneficial biological functions beyond their antioxidative properties and are involved in regulation of cell survival pathways leading to anticarcinogenic and antimutagenic functions. There are sufficient evidence from in vitro, in vivo, and epidemiological studies to suggest that the dietary intervention of polyphenols in cancer prevention, including the chemopreventive ability of dietary polyphenols, act against lung carcinogens. Cohort and epidemiological studies in selected risk populations have evaluated clinical effects of polyphenols. Polyphenols have demonstrated three major actions: antioxidative activity, regulation of phase I and II enzymes, and regulation of cell survival pathways against lung carcinogenesis. They have also shown an inverse association of lung cancer occurrences among high risk populations who consumed considerable amounts of fruits and vegetables in their daily diet. In in vitro cell culture experimental models, polyphenols bind with electrophilic metabolites from carcinogens, inactivate cellular oxygen radicals, prevent membrane lipid peroxidation and DNA oxidative damage, and adduct formation. Further, polyphenols enhance the detoxifying enzymes such as the phase II enzymes, glutathione transferases and glucuronosyl transferases.

  9. Chemoprevention of Lung Cancer

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    Szabo, Eva; Mao, Jenny T.; Lam, Stephen; Reid, Mary E.

    2013-01-01

    Background: Lung cancer is the most common cause of cancer death in men and women in the United States. Cigarette smoking is the main risk factor. Former smokers are at a substantially increased risk of developing lung cancer compared with lifetime never smokers. Chemoprevention refers to the use of specific agents to reverse, suppress, or prevent the process of carcinogenesis. This article reviews the major agents that have been studied for chemoprevention. Methods: Articles of primary, secondary, and tertiary prevention trials were reviewed and summarized to obtain recommendations. Results: None of the phase 3 trials with the agents β-carotene, retinol, 13-cis-retinoic acid, α-tocopherol, N-acetylcysteine, acetylsalicylic acid, or selenium has demonstrated beneficial and reproducible results. To facilitate the evaluation of promising agents and to lessen the need for a large sample size, extensive time commitment, and expense, surrogate end point biomarker trials are being conducted to assist in identifying the most promising agents for later-stage chemoprevention trials. With the understanding of important cellular signaling pathways and the expansion of potentially important targets, agents (many of which target inflammation and the arachidonic acid pathway) are being developed and tested which may prevent or reverse lung carcinogenesis. Conclusions: By integrating biologic knowledge, additional early-phase trials can be performed in a reasonable time frame. The future of lung cancer chemoprevention should entail the evaluation of single agents or combinations that target various pathways while working toward identification and validation of intermediate end points. PMID:23649449

  10. Cancer chemoprevention by natural compounds

    OpenAIRE

    スズキ, マスミ; Masumi, SUZUI

    2007-01-01

    There is growing interest in the use of natural compounds for the treatment and prevention of a wide variety of diseases, including cancer. Several herb-derived components are currently evaluated in preclinical studies as potential cancer chemopreventive agents. We have recently found that several herbal plants in the Ryukyu Islands, or any other natural compound, have a potential chemopreventive effect on biomarkers of colon carcinogenesis and a growth inhibitory effect on human cancer cells...

  11. Natural products for cancer-targeted therapy: citrus flavonoids as potent chemopreventive agents.

    Science.gov (United States)

    Meiyanto, Edy; Hermawan, Adam; Anindyajati

    2012-01-01

    Targeted therapy has been a very promising strategy of drug development research. Many molecular mechanims of diseases have been known to be regulated by abundance of proteins, such as receptors and hormones. Chemoprevention for treatment and prevention of diseases are continuously developed. Pre-clinical and clinical studies in chemoprevention field yielded many valuable data in preventing the onset of disease and suppressing the progress of their growth, making chemoprevention a challenging and a very rational strategy in future researches. Natural products being rich of flavonoids are those fruits belong to the genus citrus. Ethanolic extract of Citrus reticulata and Citrus aurantiifolia peels showed anticarcinogenic, antiproliferative, co-chemotherapeutic and estrogenic effects. Several examples of citrus flavonoids that are potential as chemotherapeutic agents are tangeretin, nobiletin, hesperetin, hesperidin, naringenin, and naringin. Those flavonoids have been shown to possess inhibition activity on certain cancer cells' growth through various mechanisms. Moreover, citrus flavonoids also perform promising effect in combination with several chemotherapeutic agents against the growth of cancer cells. Some mechanisms involved in those activities are through cell cycle modulation, antiangiogenic effect, and apoptosis induction. Previous studies showed that tangeretin suppressed the growth of T47D breast cancer cells by inhibiting ERK phosphorylation. While in combination with tamoxifen, doxorubicin, and 5-FU, respectively, it was proven to be synergist on several cancer cells. Hesperidin and naringenin increased cytotoxicitity of doxorubicin on MCF-7 cells and HeLa cells. Besides, citrus flavonoids also performed estrogenic effect in vivo. One example is hesperidin having the ability to decrease the concentration of serum and hepatic lipid and reduce osteoporosis of ovariectomized rats. Those studies showed the great potential of citrus fruits as natural product

  12. Flavonoids as Chemopreventive and Therapeutic Agents Against Lung Cancer

    Directory of Open Access Journals (Sweden)

    Albert Cabrera

    2014-05-01

    Full Text Available The objective of the present review is to study the relationship between flavonoids and lung cancer, proposing that their regular consumption in Western diets could be beneficial for protecting patients against lung cancer. An extensive search of the scientific literature was performed in the following electronic specialized databases (PubMed central (PMC-NBCI, Elsevier Journal, SciELO Spain, Scirus, Science Direct, including studies in animals, cells, and humans, in order to establish the effect of flavonoids in the prevention and development of lung cancer. Although in vitro and animal studies show the potential ability of flavonoids to act against different types of cancers, especially against lung cancers, the diverse results reported within epidemiological studies, together with the lack of experiments in humans, are the major factors in limiting making dietary recommendations based on scientific evidence for the management of patients with lung cancer. Therefore, the authors of the present study recommend following the dietary health practice guidelines which promotes the consumption of food enriched in flavonoids and reflects the current state of knowledge of an effective and appropriate diet in lung cancer patients.Erratum in: Rev Esp Nutr Hum Diet. 2013;17(2:91-92Link: http://www.renhyd.org/index.php/renhyd/article/view/6/17

  13. Dietary pterostilbene is a novel MTA1-targeted chemopreventive and therapeutic agent in prostate cancer

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    Zhang, Liangfen; Rimando, Agnes M.; Lage, Janice M.; Lewin, Jack R.; Atfi, Azeddine; Zhang, Xu; Levenson, Anait S.

    2016-01-01

    Overexpression of the epigenetic modifier metastasis-associated protein 1 (MTA1) is associated with aggressive human prostate cancer. The purpose of this study was to determine MTA1- targeted chemopreventive and therapeutic efficacy of pterostilbene, a natural potent analog of resveratrol, in pre-clinical models of prostate cancer. Here, we show that high levels of MTA1 expression in Pten-loss prostate cooperate with key oncogenes, including c-Myc and Akt among others, to promote prostate cancer progression. Loss-of-function studies using human prostate cancer cells indicated direct involvement of MTA1 in inducing inflammation and epithelial-to-mesenchymal transition. Importantly, pharmacological inhibition of MTA1 by pterostilbene resulted in decreased proliferation and angiogenesis and increased apoptosis. This restrained prostatic intraepithelial neoplasia (PIN) formation in prostate-specific Pten heterozygous mice and reduced tumor development and progression in prostate-specific Pten-null mice. Our findings highlight MTA1 as a key upstream regulator of prostate tumorigenesis and cancer progression. More significantly, it offers pre-clinical proof for pterostilbene as a promising lead natural agent for MTA1-targeted chemopreventive and therapeutic strategy to curb prostate cancer. PMID:26943043

  14. Tea: age-old beverage as an effective cancer chemopreventive agent

    Directory of Open Access Journals (Sweden)

    Jasmine George

    2011-12-01

    Full Text Available Cancer is the major public health problem, causing approximately 7 million deaths every year worldwide. The existing treatment approaches and surgical techniques have not been able to cope effectively with this dreaded disease. Because of this, the concept of chemoprevention is now considered a valid approach to reduce the incidence of cancer. There is convincing epidemiological and experimental evidence to show that dietary polyphenolic plant-derived compounds have cancer preventive properties. Based on evidence from in vitro, in vivo data and epidemiological studies, tea has received considerable attention over recent years for reducing the risk of several cancers. Much of the cancer preventive effects of tea, and in particular green tea, appear to be mediated by the polyphenols they contain. In addition to inhibiting mutagenesis and proliferation, tea is relatively non-toxic, is low cost, and can be taken orally or as a part of the daily diet. Therefore it is logical that future clinical studies should focus on examining the efficacy of tea and its active constituents, such as epigallocatechin- 3-gallate (EGCG and theaflavins (TFs, in chemoprevention as an alternative to pharmacological agents. In this review, we address the use of tea and its constituents for the prevention and treatment of cancer. Further mechanistic and dose-response studies will help us to understand the effects of tea consumption on human carcinogenesis.

  15. Natural Products as a Vital Source for the Discovery of Cancer Chemotherapeutic and Chemopreventive Agents.

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    Cragg, Gordon M; Pezzuto, John M

    2016-01-01

    Throughout history, natural products have played a dominant role in the treatment of human ailments. For example, the legendary discovery of penicillin transformed global existence. Presently, natural products comprise a large portion of current-day pharmaceutical agents, most notably in the area of cancer therapy. Examples include Taxol, vinblastine, and camptothecin. These structurally unique agents function by novel mechanisms of action; isolation from natural sources is the only plausible method that could have led to their discovery. In addition to terrestrial plants as sources for starting materials, the marine environment (e.g., ecteinascidin 743, halichondrin B, and dolastatins), microbes (e.g., bleomycin, doxorubicin, and staurosporin), and slime molds (e.g., epothilone B) have yielded remarkable cancer chemotherapeutic agents. Irrespective of these advances, cancer remains a leading cause of death worldwide. Undoubtedly, the prevention of human cancer is highly preferable to treatment. Cancer chemoprevention, the use of vaccines or pharmaceutical agents to inhibit, retard, or reverse the process of carcinogenesis, is another important approach for easing this formidable public health burden. Similar to cancer chemotherapeutic agents, natural products play an important role in this field. There are many examples, including dietary phytochemicals such as sulforaphane and phenethyl isothiocyanate (cruciferous vegetables) and resveratrol (grapes and grape products). Overall, natural product research is a powerful approach for discovering biologically active compounds with unique structures and mechanisms of action. Given the unfathomable diversity of nature, it is reasonable to suggest that chemical leads can be generated that are capable of interacting with most or possibly all therapeutic targets. © 2015 S. Karger AG, Basel.

  16. Chemoprevention of bladder cancer.

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    Kamat, Ashish M; Lamm, Donald L

    2002-02-01

    The data presented herein, although highly supportive for a protective role of various nutrients against bladder cancer, are far from definitive. Many authorities question the validity of current recommendations for nutritional chemoprevention against bladder cancer. The reason for the wide variations reported in epidemiologic studies lies in the nature of observational studies. Dietary studies are limited in their conclusions because the protection afforded by the consumption of a particular nutrient may be multifactorial, with different components of the food exerting potential chemopreventive effects. Furthermore, measuring levels of nutrients in the food intake of populations is confounded by factors that might affect these levels and also the incidence of cancer. For example, vitamin A can come from animal or vegetarian sources. Because animal fat has been identified as a potential carcinogen in man, depending on the source of the vitamin, varying levels of protection might be deduced. In addition, chemoprevention studies using dietary supplements are expected to have mild effects, and large studies would be required to confirm statistical significance. Even with agents such as intravesical chemotherapy, only half the studies achieve statistical significance [29]. Prospective randomized trials with a large sample size, longer follow-up, and an extended duration of treatment are needed to clarify the association between micronutrients and cancer protection. With these caveats in mind, several recommendations can be made. Simple measures, such as drinking more fluids (especially water), can have a profound impact on the incidence of bladder cancer. Vitamins are being extensively studied in chemopreventive trials for different cancers. There is strong evidence for a chemoprotective effect of vitamin A in bladder cancer. The authors recommend 32,000 IU/day of vitamin A initially, with lower doses (24,000 IU) for persons less than 50 kg. Because liver toxicity is a

  17. Antibody Array as a Tool for Screening of Natural Agents in Cancer Chemoprevention.

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    Pulito, Claudio; Sacconi, Andrea; Korita, Etleva; Maidecchi, Anna; Strano, Sabrina

    2016-01-01

    The efficacy of a given drug resides mainly on its ability to specifically target disease mechanisms. Natural products represent the leading source of bioactive molecules with a broad range of activities. It is becoming increasingly clear that natural compounds exert their chemopreventive or antitumoral activities targeting simultaneously diverse cellular pathways. Here we describe the use of antibody array to assess the effects of natural compounds on the expression of multiple proteins and of their posttranslational modifications in cellular systems. This might turn to be a very flexible application for cancer chemoprevention studies.

  18. Dietary pterostilbene is a novel MTA1-targeted chemopreventive and therapeutic agent in prostate cancer

    OpenAIRE

    Dhar, Swati; Kumar, Avinash; Zhang, Liangfen; Rimando, Agnes M.; Lage, Janice M.; Lewin, Jack R.; Atfi, Azeddine; Zhang, Xu; Levenson, Anait S.

    2016-01-01

    Overexpression of the epigenetic modifier metastasis-associated protein 1 (MTA1) is associated with aggressive human prostate cancer. The purpose of this study was to determine MTA1- targeted chemopreventive and therapeutic efficacy of pterostilbene, a natural potent analog of resveratrol, in pre-clinical models of prostate cancer. Here, we show that high levels of MTA1 expression in Pten-loss prostate cooperate with key oncogenes, including c-Myc and Akt among others, to promote prostate can...

  19. Development of novel cancer chemopreventive agents in Europe--neglected Cinderella or rising phoenix? A critical commentary. ESF Workshop on Cancer Chemoprevention, DKFZ, Heidelberg, September 18-20, 2005.

    Science.gov (United States)

    Gerhauser, Clarissa; Bartsch, Helmut; Crowell, James; De Flora, Silvio; D'Incalci, Maurizio; Dittrich, Christian; Frank, Norbert; Mihich, Enrico; Steffen, Christian; Tortora, Giampaolo; Gescher, Andreas

    2006-07-01

    Agents that prevent cancer, delay its onset, or revert premalignant conditions could have dramatic beneficial impacts on human health. Although there is an urgent need to develop cancer chemopreventive agents, researchers in the field suspect that this area of scientific endeavour in Europe leads a Cinderella existence, both in terms of perception of importance and research funding. In order to review current activities in this prevention field and to seek a consensus position, an exploratory workshop was held in September 2005 at the German Cancer Research Center (DKFZ) in Heidelberg, Germany, sponsored mainly by the European Science Foundation (ESF), and also supported by the European Association for Cancer Research (EACR) and the German Cancer Society (DKG). The 35 experts from European countries and the United States of America assessed state-of-the-art cancer chemoprevention research in Europe. The aims that the workshop organizers had pre-defined were: i) assessment of the usefulness of animal models for agent identification; ii) review of ongoing preclinical and clinical work on novel agents; iii) discussion of potential biomarkers predictive for cancer preventive efficacy; and finally iv) the potential role that European pharmaceutical industries could play in furthering chemopreventive agent development. Overall the workshop aimed at raising awareness among European clinical and laboratory researchers of the importance of the development of novel, efficacious and safe cancer preventive agents.

  20. [Coffee in Cancer Chemoprevention].

    Science.gov (United States)

    Neuwirthová, J; Gál, B; Smilek, P; Urbánková, P

    Coffee consumption is associated with a reduced risk of several diseases including cancer. Its chemopreventive effect has been studied in vitro, in animal models, and more recently in humans. Several modes of action have been proposed, namely, inhibition of oxidative stress and damage, activation of metabolizing liver enzymes involved in carcinogen detoxification processes, and anti-inflammatory effects. The antioxidant activity of coffee relies partly on its chlorogenic acid content and is increased during the roasting process. Maximum antioxidant activity is observed for medium-roasted coffee. The roasting process leads to the formation of several components, e.g., melanoidins, which have antioxidant and anti-inflammatory properties. Coffee also contains two specific diterpenes, cafestol and kahweol, which have anticarcinogenic properties. Roasted coffee is a complex mixture of various chemicals. Previous studies have reported that the chemopreventive components present in coffee induce apoptosis, inhibit growth and metastasis of tumor cells, and elicit antiangiogenic effects. A meta-analysis of epidemiological studies showed that coffee consumption is associated with a lower risk of developing various malignant tumors. This review summarizes the molecular mechanisms and the experimental and epidemiological evidence supporting the chemopreventive effect of coffee.Key words: coffee - chemoprevention - antioxidative enzyme - detoxification enzyme - anti-inflammatory effect The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 11. 9. 2016Accepted: 24. 11. 2016.

  1. Clove (Syzygium aromaticum L.), a potential chemopreventive agent for lung cancer.

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    Banerjee, Sarmistha; Panda, Chinmay Kr; Das, Sukta

    2006-08-01

    Spices and flavoring plants part rich in supposedly health-promoting phytochemicals are currently receiving much attention as a possible source of cancer chemopreventive compounds. Clove, the sun-dried unopened flower bud from the plant Syzygium aromaticum L. is a commonly used spice and food flavor. In the present work we assess the chemopreventive potential of aqueous infusion of clove during benzo[a]pyrene (BP)-induced lung carcinogenesis in strain A mice. Incidence of hyperplasia, dysplasia and carcinoma in situ evident in the carcinogen control group on the 8th, 17th and 26th weeks, respectively, were effectively reduced after treatment with clove infusion. Significant reduction in the number of proliferating cells and an increased number of apoptotic cells was also noted in these BP-induced lung lesions following clove treatment. Western blotting analysis revealed that clove infusion upregulates the expression of pro-apoptotic proteins p53 and Bax, and downregulates the expression of anti-apoptotic protein Bcl-2 in the precancerous stages. Expression of caspase 3 and its activation by clove infusion were evident from a very early stage of carcinogenesis (eighth week). Clove infusion was also found to downregulate the expression of some growth-promoting proteins, viz, COX-2, cMyc, Hras. The observations signify the chemopreventive potential of clove in view of its apoptogenic and anti-proliferative properties.

  2. Beneficial and adverse effects of chemopreventive agents

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Byung Mu; Park, Kwang-Kyun

    2003-03-01

    The beneficial and adverse effects of some chemopreventive agents, such as Vitamins A, C, E, beta-carotene, indole-3-carbinol, capsaicin, garlic, and aloe are reviewed. Two large randomized trials with a lung cancer endpoint, the Alpha-Tocopherol, Beta-Carotene (ATBC) Prevention Study and the Beta-Carotene and Retinol Efficacy Trial (CARET), suggested that antioxidants might be harmful in smokers. However, the results of the Linxian study and of the ATBC or the CARET studies were significantly different in this respect, and therefore, the relationship between antioxidant and carcinogenesis remains open to debate. Indole-3-carbinol has cancer promoting activities in the colon, thyroid, pancreas, and liver, whereas capsaicin alters the metabolism of chemical carcinogens and may promote carcinogenesis at high doses. Organosulfur compounds and selenium from garlic have no or a little enhancing effect on cancer promotion stage. Information upon chemopreventive mechanisms that inhibit carcinogenesis is imperfect, although the causes and natures of certain human cancers are known. Therefore, definitive preventive guidelines should be carefully offered for various types of tumors, which properly consider ethnic variations, and the efficacies and the safety of chemopreventive agents.

  3. Cancer chemoprevention – selected molecular mechanisms

    Directory of Open Access Journals (Sweden)

    Katarzyna Walczak

    2017-03-01

    Full Text Available The effect of diet on cancer formation and prevention of carcinogenesis has attracted considerable attention for years and is the subject of several studies. Some components of the daily diet, such as resveratrol, curcumin, genistein, gingerol, can significantly reduce the risk of cancer or affect the rate of tumor progression. Cancer chemoprevention assumes the use of natural or synthetic biologically active substances in order to prevent, inhibit or reverse the progression of cancer. There are many biologically active compounds in several natural products, i.e. garlic, ginger, soy, curcuma, tomatoes, cruciferous plants or green tea. Their chemopreventive activity is based on the inhibition of processes underlying carcinogenesis (inflammation, transformation and proliferation, but also affects the final phase of carcinogenesis - angiogenesis and metastasis. Despite the relatively low toxicity of chemopreventive agents, their molecular targets often coincide with the objectives of the currently used cancer therapies. The widespread use of chemopreventive agents may contribute to reduction of the rate of cancer incidence, and increase the effectiveness of conventional cancer therapies. In the present study, selected molecular mechanisms of the chemopreventive activity have been discussed, especially their involvement in the regulation of signal transduction, cell cycle regulation, apoptosis, metastasis and angiogenesis. The role of chemopreventive agents in the inflammatory process, the metabolism of xenobiotics and multidrug resistance has been also characterized.

  4. Comet Assay in Cancer Chemoprevention.

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    Santoro, Raffaela; Ferraiuolo, Maria; Morgano, Gian Paolo; Muti, Paola; Strano, Sabrina

    2016-01-01

    The comet assay can be useful in monitoring DNA damage in single cells caused by exposure to genotoxic agents, such as those causing air, water, and soil pollution (e.g., pesticides, dioxins, electromagnetic fields) and chemo- and radiotherapy in cancer patients, or in the assessment of genoprotective effects of chemopreventive molecules. Therefore, it has particular importance in the fields of pharmacology and toxicology, and in both environmental and human biomonitoring. It allows the detection of single strand breaks as well as double-strand breaks and can be used in both normal and cancer cells. Here we describe the alkali method for comet assay, which allows to detect both single- and double-strand DNA breaks.

  5. DIETARY TERPENOIDS AND PROSTATE CANCER CHEMOPREVENTION

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    Rabi, Thangaiyan; Gupta, Sanjay

    2014-01-01

    Cancer chemoprevention by phytochemicals may be one of the most feasible approaches for cancer control. Phytochemicals obtained from vegetables, fruits, spices, teas, herbs and medicinal plants, such as terpenoids and other phenolic compounds, have been proven to suppress experimental carcinogenesis in various organs in pre-clinical models. Recent studies have indicated that mechanisms underlying chemopreventive potential may be a combination of antioxidant, anti-inflammatory, immune-enhancing, and hormone modulation effects, with modification of drug metabolizing enzymes, influence on cell cycle and cell differentiation, induction of apoptosis, suppression of proliferation and angiogenesis playing roles in the initiation and secondary modification stages of neoplastic development. Specific features of prostate cancer, such as high prevalence and long latency period provides ample opportunities for chemopreventive agents to work at various stages of disease progression. Finally, suitable populations with appropriate risk factors, including the presence of pre-malignant lesions and genetic predispositions, need to be well characterized for future chemopreventive interventions. Here we review naturally occurring dietary terpenoids as useful agents for prostate cancer chemoprevention with reference to their classes and sources. PMID:18508447

  6. Meeting Report: Pancreatic Cancer Chemoprevention Translational Workshop

    Science.gov (United States)

    Miller, Mark Steven; Allen, Peter; Brentnall, Teresa; Goggins, Michael; Hruban, Ralph H.; Petersen, Gloria M.; Rao, Chinthalapally V.; Whitcomb, David C.; Brand, Randall E.; Chari, Suresh; Klein, Alison; Lubman, David; Rhim, Andrew; Simeone, Diane M.; Wolpin, Brian; Umar, Asad; Srivastava, Sudhir; Steele, Vernon E.; Ann Rinaudo, Jo

    2016-01-01

    Pancreatic cancer is the 4th leading cause of cancer related deaths in the US with a 5 year survival rate of Cancer Prevention of the NCI sponsored the Pancreatic Cancer Chemoprevention Translational Workshop on September 10–11th 2015. The goal of the workshop was to obtain information regarding the current state of the science and future scientific areas that should be prioritized for pancreatic cancer prevention research, including early detection and intervention for high-risk precancerous lesions. The workshop addressed the molecular/genetic landscape of pancreatic cancer and precursor lesions; high risk populations and criteria to identify a high risk population for potential chemoprevention trials; identification of chemopreventative/immuopreventative agents; and use of potential biomarkers and imaging for assessing short term efficacy of a preventative agent. The field of chemoprevention for pancreatic cancer is emerging and this workshop was organized to begin to address these important issues and promote multi-institutional efforts in this area. The meeting participants recommended the development of an NCI working group to coordinate efforts, provide a framework, and identify opportunities for chemoprevention of pancreatic cancer. PMID:27518363

  7. Colon Cancer Chemoprevention by Flavonoid Silibinin | Division of Cancer Prevention

    Science.gov (United States)

    DESCRIPTION (provided by applicant): Cancer stem cells (CSC) are now recognized as the main cause for initiation, promotion and progression of most of the cancers, including colorectal cancer (CRC). Despite this fact, efficacy of chemopreventive agents towards CSC generation leading to cancer initiation and tumorigenesis has not yet been well- defined. |

  8. Speciation and bioavailability of selenium in yeast-based intervention agents used in cancer chemoprevention studies

    DEFF Research Database (Denmark)

    Larsen, Erik Huusfeldt; Hansen, Marianne; Paulin, H.

    2004-01-01

    This study investigated the speciation and bioavailability of selenium in yeast-based intervention agents from multiple manufacturers from several time points. Sources of selenized yeast included Nutrition 21 (San Diego, CA), which supplied the Nutritional Prevention of Cancer (NPC) Trial from 1981......-1996; Cypress Systems (Fresno, CA; 1997-1999); and Pharma Nord (Vejle, Denmark; 1999-2000), which supplied the Prevention of Cancer by Intervention by Selenium (PRECISE) Trial pilot studies. The low-molecular-selenium species were liberated from the samples by proteolytic hydrolysis followed by separation...... at 54-60% of the total selenium in the yeasts. One batch of yeast, however (from 1985), which originated from the same producer as the yeast used in the NPC tablets, contained only 27% of selenium in the sample as selenomethionine. Human subjects receiving 200 mug selenium/day in the UK PRECISE Pilot...

  9. Topical polyethylene glycol as a novel chemopreventive agent for oral cancer via targeting of epidermal growth factor response.

    Directory of Open Access Journals (Sweden)

    Ramesh K Wali

    Full Text Available Head and neck squamous cell carcinoma (HNSCC is a major cause of morbidity and mortality underscoring the need for safe and effective chemopreventive strategies. Targeting epidermal growth factor receptor (EGFR is attractive in that it is an early critical event in HNSCC pathogenesis. However, current agents lack efficacy or have unacceptable toxicity. Several groups have demonstrated that the over-the-counter medication, polyethylene glycol (PEG has remarkable chemopreventive efficacy against colon carcinogenesis. Importantly, we reported that this effect is mediated through EGFR internalization/degradation. In the current study, we investigated the chemopreventive efficacy of this agent against HNSCC, using both the well validated animal model 4-NQO (4-nitroquinoline 1-oxide rat model and cell culture with the human HNSCC cell line SCC-25. We demonstrated that daily topical application of 10% PEG-8000 in the oral cavity (tongue and cavity wall post 4NQO initiation resulted in a significant reduction in tumor burden (both, tumor size and tumors/tumor bearing rat without any evidence of toxicity. Immunohistochemical studies depicted decreased proliferation (number of Ki67-positive cells and reduced expression of EGFR and its downstream effectors cyclin D1 in the tongue mucosa of 4NQO-rats treated with PEG. We showed that EGFR was also markedly downregulated in SCC-25 cells by PEG-8000 with a concomitant induction of G1-S phase cell-cycle arrest, which was potentially mediated through upregulated p21(cip1/waf1. In conclusion, we demonstrate, for the first time, that PEG has promising efficacy and safety as a chemopreventive efficacy against oral carcinogenesis.

  10. Cancer chemoprevention by targeting the epigenome.

    Science.gov (United States)

    Huang, Joseph; Plass, Christoph; Gerhauser, Clarissa

    2011-12-01

    The term "epigenetics" refers to modifications in gene expression caused by heritable, but potentially reversible, changes in DNA methylation and chromatin structure. Given the fact that epigenetic modifications occur early in carcinogenesis and represent potentially initiating events in cancer development, they have been identified as promising new targets for prevention strategies. The present review will give a comprehensive overview of the current literature on chemopreventive agents and their influence on major epigenetic mechanisms, that is DNA methylation, histone acetylation and methylation, and microRNAs, both in vitro and in rodent and human studies, taking into consideration specific mechanisms of action, target sites, concentrations, methods used for analysis, and outcome. Chemopreventive agents with reported mechanisms targeting the epigenome include micronutrients (folate, selenium, retinoic acid, Vit. E), butyrate, polyphenols (from green tea, apples, coffee, and other dietary sources), genistein and soy isoflavones, parthenolide, curcumin, ellagitannin, indol-3-carbinol (I3C) and diindolylmethane (DIM), mahanine, nordihydroguaiaretic acid (NDGA), lycopene, sulfur-containing compounds from Allium and cruciferous vegetables (sulforaphane, phenylethyl isothiocyanate (PEITC), phenylhexyl isothiocyanate (PHI), diallyldisulfide (DADS), allyl mercaptan (AM)), antibiotics (mithramycin A, apicidin), pharmacological agents (celecoxib, DFMO, 5-aza-2'-deoxycytidine and zebularine), compounds affecting sirtuin activity (resveratrol, dihydrocoumarin, cambinol), inhibitors of histone acetyl transferases (anacardic acid, garcinol, ursodeoxycholic acid), and relatively unexplored modulators of histone lysine methylation (chaetocin, polyamine analogues, n-3 polyunsaturated fatty acids). Their effects on global DNA methylation, tumor suppressor genes silenced by promoter methylation, histone modifications, and miRNAs deregulated during carcinogenesis have potential

  11. Diallyl trisulfide, a chemopreventive agent from Allium vegetables, inhibits alpha-secretases in breast cancer cells.

    Science.gov (United States)

    Kiesel, Violet A; Stan, Silvia D

    2017-03-18

    Breast cancer affects one in eight women throughout the course of their lifetime creating a demand for novel prevention strategies against this disease. The Notch signaling pathway is often aberrantly activated in human malignancies including breast cancer. Alpha secretases, including ADAM (A Disintegrin and Metalloprotease) -10 and -17, are proteases that play a key role in the cleavage of cell surface molecules and subsequent ligand-mediated activation of Notch signaling pathway. High expression levels of ADAM10 and 17 have been clinically associated with a lower disease-free survival in breast cancer patients. This study was undertaken to determine the effect of diallyl trisulfide (DATS), a bioactive organosulfide found in garlic and other Allium vegetables, on alpha secretases in breast cancer cells. Here we report for the first time that DATS inhibits the expression of ADAM10 and ADAM17 in estrogen-independent MDA-MB-231 and estrogen-dependent MCF-7 breast cancer cells, and in Harvey-ras (H-Ras) transformed MCF10A-H-Ras breast epithelial cells. We also show that DATS induces a dose-dependent reduction in colony formation ability of MDA-MB-231 and MCF-7 cells, suggesting a long-term effect of DATS on growth inhibition of breast cancer cells. Furthermore, we show that DATS inhibits the Notch ligands Jagged-1 and Jagged-2 involved in activation of Notch signaling pathway. Collectively, these findings show that DATS targets Notch pathway components overexpressed in breast cancer tumors and may serve as a functionally relevant bioactive for breast cancer prevention. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Nitric oxide-releasing sulindac is a novel skin cancer chemopreventive agent for UVB-induced photocarcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Chaudhary, Sandeep C.; Singh, Tripti; Kapur, Puneet; Weng, Zhiping; Arumugam, Aadithya; Elmets, Craig A. [Department of Dermatology, University of Alabama at Birmingham, 1530 3rd Avenue South, VH509, Birmingham, AL 35294-0019 (United States); Kopelovich, Levy [Division of Cancer Prevention, National Cancer Institute, 6130 Executive Blvd, Suite 2114, Bethesda, MD 20892 (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology, University of Alabama at Birmingham, 1530 3rd Avenue South, VH509, Birmingham, AL 35294-0019 (United States)

    2013-05-01

    Nitric oxide (NO)-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) which have been synthesized to reduce gastro-intestinal and cardiovascular toxicities of NSAIDs, possess anti-proliferative, pro-apoptotic and anti-cancer activities. Here, we show that NO-sulindac inhibited UVB-induced skin tumorigenesis in SKH-1 hairless mice. Topical application of NO-sulindac reduced tumor incidence, number (p < 0.05) and volume (p < 0.005) as compared to UVB (alone)-irradiated vehicle-treated mice. An increase in TUNEL-positive cells in skin lesions was accompanied by the enhanced Bax:Bcl-2 ratio. The expression of pro-apoptotic Bax was increased whereas anti-apoptotic Bcl-2 reduced. However, proliferation was identified as the major target of NO-sulindac in this study. A reduced expression of PCNA and cyclin D1 associated with the dampening of cell cycle progression was observed. The mechanism of this inhibition was related to the reduction in UVB-induced Notch signaling pathway. UVB-induced inflammatory responses were diminished by NO-sulindac as observed by a remarkable reduction in the levels of phosphorylated MAP Kinases Erk1/2, p38 and JNK1/2. In this regard, NO-sulindac also inhibited NFκB by enhancing IκBα as evidenced by the reduced expression of iNOS and COX-2, the direct NFκB transcription target proteins. NO-sulindac significantly diminished the progression of benign lesions to invasive carcinomas by suppressing the tumor aggressiveness and retarding epithelial–mesenchymal transition. A marked decrease in the expression of mesenchymal markers such as Fibronectin, N-cadherin, SNAI, Slug and Twist and an increase in epithelial cell polarity marker E-cadherin were noted in NO-sulindac-treated tumors. Our data suggest that NO-sulindac is a potent inhibitor of UVB-induced skin carcinogenesis and acts by targeting proliferation-regulatory pathways. - Highlights: ► NO-sulindac is a potent chemopreventive agent for UVB-induced skin cancer. ► NO

  13. Synthesis of novel carbazole chalcones as radical scavenger, antimicrobial and cancer chemopreventive agents.

    Science.gov (United States)

    Bandgar, Babasaheb P; Adsul, Laxman K; Lonikar, Shrikant V; Chavan, Hemant V; Shringare, Sadanand N; Patil, Sachin A; Jalde, Shivkumar S; Koti, Basawaraj A; Dhole, Nagesh A; Gacche, Rajesh N; Shirfule, Amol

    2013-06-01

    A series of novel carbazole chalcones has been synthesised and evaluated for radical scavenging activity, cytotoxicity and antimicrobial activities. Compounds 12m, 12o and 12c exhibited good 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, compounds 12e, 12m and 12d were excellent hydroxyl radical scavengers and compounds 12a, 12e, 12g, 12n and 12m have shown inhibition of oxidative DNA damage induced by 2,2'-azobis (2-amidinopropane hydrochloride). Compounds 12j, 12i, 12n, 12c, 12m and 12e were most active against the selected cancer cell lines. Compounds 12a, 12e and 12m showed good antibacterial activity and compounds 12h and 12m have shown good antifungal activity. All the compounds were subjected for absorption, distribution, metabolism and excretion (ADME) predictions by computational method and found that these molecules could be considered as potential candidates for oral drug development.

  14. New rodent models for studies of chemopreventive agents.

    Science.gov (United States)

    Lipkin, M

    1997-01-01

    Some recent studies of the effects of chemopreventive agents have begun to use new rodent models to improve the analysis of stages of colonic preneoplasia, and how chemopreventive agents modify progressive abnormal cell development. In one of the models of inherited predisposition to colon cancer, mice carrying a truncated Apc allele with a nonsense mutation in exon 15 have been generated by gene targeting and embryonic stem cell technology (Apc1638 mice). These mice develop multiple gastrointestinal lesions, including adenomas and carcinomas, focal areas of high-grade dysplasia (FAD), and polypoid hyperplasias with FADS. The incidence of inherited colonic neoplasms has now been modulated by a chemopreventive regimen. Colonic lesions significantly increased in Apc1638 mice on a Western-style diet, which has higher fat content and lower calcium and vitamin D compared to the same mice on AIN-76A diet. In another rodent model, Min mice were treated with sulindac, which markedly reduced the incidence of intestinal tumors. A third new rodent model containing a targeted mutation in the gene Mcc (mutated in colorectal cancer) recently became available for chemoprevention studies. These mice develop multiple types of neoplasms including adenocarcinomas, focal areas of gastrointestinal dysplasia, papillomas of the forestomach, and tumors in other organs including lung, liver, and lymphoid tissue. Feeding a Western-style diet to the Mcc mutant mice also resulted in significantly increased gastrointestinal lesions. These nutrient modifications also have been given to normal mice, demonstrating without any chemical carcinogen that a Western-style diet induced colonic tumorigenesis. Western-style diets also have now induced modulation of cell proliferation in other organs including mammary gland, pancreas, and prostate. These findings help develop new preclinical rodent models to aid the analysis of genetic and environmental factors leading to neoplasia, as well as new methods

  15. Nicotinamide for skin cancer chemoprevention.

    Science.gov (United States)

    Damian, Diona L

    2017-08-01

    Nicotinamide (vitamin B 3 ) has a range of photoprotective effects in vitro and in vivo; it enhances DNA repair, reduces UV radiation-induced suppression of skin immune responses, modulates inflammatory cytokine production and skin barrier function and restores cellular energy levels after UV exposure. Pharmacological doses of nicotinamide have been shown to reduce actinic keratoses and nonmelanoma skin cancer incidence in high-risk individuals, making this a nontoxic and accessible option for skin cancer chemoprevention in this population. © 2017 The Australasian College of Dermatologists.

  16. Chemoprevention of cancer: current evidence and future prospects [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Vassiliki Benetou

    2015-09-01

    Full Text Available Cancer chemoprevention refers to the use of agents for the inhibition, delay, or reversal of carcinogenesis before invasion. In the present review, agents examined in the context of cancer chemoprevention are classified in four major categories—hormonal, medications, diet-related agents, and vaccines—and the main representatives of each category are presented. Although there are serious constraints in the documentation of effectiveness of chemopreventive agents, mainly stemming from the long latency of the condition they are addressing and the frequent lack of intermediate biomarkers, there is little disagreement about the role of aspirin, whereas a diet rich in vegetables and fruits appears to convey more protection than individual micronutrients. Among categories of cancer chemopreventive agents, hormonal ones and vaccines might hold more promise for the future. Also, the identification of individuals who would benefit most from chemopreventive interventions on the basis of their genetic profiles could open new prospects for cancer chemoprevention.

  17. Chemoprevention of Ovarian Cancer

    Science.gov (United States)

    2005-10-01

    described. 8 We used DNA chip technology to identify gene expression in the Genomics Core Laboratory at the University of Texas Health Sciences Center...and Tucker, M. The risk ofscribed above, genomic and proteomic methods are now being cancer associated with specific mutations of BRCAI and BRCA2...Bentley, R. C., effctie gaista humain ovariatn carcinoma xenograft and potentiates Walmer, D. K., Cline, M., Whitaker, R. S., Istier, P., Berchuck

  18. Chemoprevention of Ovarian Cancer

    Science.gov (United States)

    2006-10-01

    Cancer Res 1998;4:1345–55. [18] Kim Y-H, Dohi DF, Han G-R, Zou CP, Oridate N, Walsh GL, et al. Retinoid refractoriness occurs during lung...Localization and kinetics of reduced pyridine nucleotide in living cells by microfluorometry. J. Biol. Chem. 234, 3044–3050. 10. Huber, R., M. Buchner ...Um, S-J., Lee, S-Y., Kim, E-J., Han , H-S., Koh, Y-M., Hong, K-J., Sin, H-S., and Park, J-S. Anti-proliferative mechanism of retinoid de- rivatives in

  19. Nigerian foodstuffs with prostate cancer chemopreventive polyphenols.

    Science.gov (United States)

    Atawodi, Sunday Eneojo

    2011-09-23

    Dietary polyphenols are antioxidants that can scavenge biological free radicals, and chemoprevent diseases with biological oxidation as their main etiological factor. In this paper, we review our laboratory data vis-ὰ-vis available literature on prostate cancer chemopreventive substances in Nigerian foodstuffs. Dacryodes edulis fruit, Moringa oleifera and Syzygium aromaticum contained prostate active polyphenols like ellagic acid, gallate, methylgallate, catechol, kaempferol quercetin and their derivatives. Also Canarium schweinfurthii Engl oil contained ten phenolic compounds and lignans, namely; catechol, p-hydroxybenzaldehyde, dihydroxyphenylacetic acid, tyrosol, p-hydroxybenzoic acid, dihydroxybenzoic acid, vanillic acid, phloretic acid, pinoresinol, secoisolariciresinol. In addition, tomatoes (Lycopersicon esculentum Mill) which contains the powerful antioxidant and anti-prostate cancer agent, lycopene; cabbage (Brassica oleracea) containing indole-3-carbinol; citrus fruits containing pectin; Soursop (Annona muricata) containing annonaceous acetogenins; soya beans (Glycine max) containing isoflavones; chilli pepper (Capsicum annuum) containing capsaicin, and green tea (Camellia sinensis) containing (-) epigallocatechin gallate (EGCG), (-) epicatechin, (-) epicatechin-3-gallate and (-) epigallocatechin -3-gallate which are widely reported to posses prostate cancer chemopreventive compounds are also grown in Nigeria and other African countries. Thus, the high incidence of prostate cancer among males of African extraction can be dramatically reduced, and the age of onset drastically increased, if the population at risk consumes the right kinds of foods in the right proportion, beginning early in life, especially as prostate cancer has a latency period of about 50 years.

  20. [The role of natural dietary compounds in colorectal cancer chemoprevention].

    Science.gov (United States)

    Olejnik, Anna; Tomczyk, Joanna; Kowalska, Katarzyna; Grajek, Włodzimierz

    2010-04-07

    This review discusses the preventive and therapeutic potential of natural dietary compounds against colorectal cancer. The chemopreventive properties of many natural food matrices and purified bioactive compounds have been evaluated. Prominent among the dietary constituents that are the focus of interest in colorectal cancer chemoprevention are dietary fiber, probiotics and prebiotics, methionine and folate, vitamins D and E, calcium and selenium, anthocyanins, procyanidins, phytoestrogens, isothiocyanates, epigallocatechin gallate, curcumin, and resveratrol. Laboratory studies provide strong evidence for the antitumor potential of these dietary agents. The mechanisms of their chemopreventive action are associated with, for example, the modulation of gene expression involved in the regulation of cell proliferation, differentiation, and apoptosis and the suppression of metastasis and angiogenesis. The anti-carcinogenic properties of these food compounds are also related to inhibition of many inflammatory agents, including the expression of cyclooxygenase-2. In vitro and animal studies showed that most of them can protect against various carcinogens mediating colon cancer and suggest that they can also sensitize tumors to chemotherapy and radiation. Although experimental studies have clearly demonstrated their anticancer activity, not many clinical trials have provided satisfying results, not only because of the lack of efficiency of the chemopreventive agents, but also due to the lack of precise biomarkers monitoring their effects on colon cancer. Despite the lack of strong evidence for the anticancer potential of natural food compounds, clinicians have high hopes for using these factors in colon cancer chemoprevention and decreasing the incidence of this common malignancy in the future.

  1. Cancer chemopreventive property of Bidens pilosa methanolic

    African Journals Online (AJOL)

    admin

    tumor growth. Chemopreventive agents can be broadly classified as blocking and suppressing agents. The blocking agents prevent carcinogenic ... stimulating differentiation in myeloid leukemia cells at a very low concentration, the effects of TPA in mouse with papilloma were investigated in the present study. In the present ...

  2. Aspirin and colorectal cancer: the promise of precision chemoprevention.

    Science.gov (United States)

    Drew, David A; Cao, Yin; Chan, Andrew T

    2016-03-01

    Aspirin (acetylsalicylic acid) has become one of the most commonly used drugs, given its role as an analgesic, antipyretic and agent for cardiovascular prophylaxis. Several decades of research have provided considerable evidence demonstrating its potential for the prevention of cancer, particularly colorectal cancer. Broader clinical recommendations for aspirin-based chemoprevention strategies have recently been established; however, given the known hazards of long-term aspirin use, larger-scale adoption of an aspirin chemoprevention strategy is likely to require improved identification of individuals for whom the protective benefits outweigh the harms. Such a precision medicine approach may emerge through further clarification of aspirin's mechanism of action.

  3. Sulforaphane (SFN: An Isothiocyanate in a Cancer Chemoprevention Paradigm

    Directory of Open Access Journals (Sweden)

    Mohammad Fahad Ullah

    2015-07-01

    Full Text Available The International Agency for Research on Cancer (IARC in its latest World Cancer Report (2014 has projected the increase in the global cancer burden from 14 million (2012 to 22 million incidence annually within the next two decades. Such statistics warrant a collaborative engagement of conventional and complementary and alternative therapies to contain and manage cancer. In recent years, there has been a shift in the cancer chemoprevention paradigm with a significant focus turning towards bioactive components of human diets for their anticancer properties. Since diet is an integral part of lifestyle and given that an estimated one third of human cancers are believed to be preventable though appropriate lifestyle modification including dietary habits, the current shift in the conventional paradigm assumes significance. Several epidemiological studies have indicated that consumption of broccoli is associated with a lower risk of cancer incidence including breast, prostate, lung, stomach and colon cancer. The edible plant belonging to the family of cruciferae such as broccoli is a rich source of glucoraphanin, a precursor of isothiocyanate sulforaphane which is considered to be a potent anti-cancer agent. Plant-based dietary agents such as sulforaphane mimic chemotherapeutic drugs such as vorinostat, possessing histone deacetylase inhibition activity. Evidence from epidemiological and experimental studies have emerged, enhancing the clinical plausibility and translational value of sulforaphane in cancer chemoprevention. The present review provides the current understanding of the cancer chemopreventive pharmacology of sulforaphane towards its potential as an anticancer agent.

  4. Endophytic fungi associated with Taxus fuana (West Himalayan Yew) of Pakistan: potential bio-resources for cancer chemopreventive agents.

    Science.gov (United States)

    Fatima, Nighat; Kondratyuk, Tamara P; Park, Eun-Jung; Marler, Laura E; Jadoon, Muniba; Qazi, Muneer Ahmed; Mehboob Mirza, Hira; Khan, Ibrar; Atiq, Naima; Chang, Leng Chee; Ahmed, Safia; Pezzuto, John M

    2016-11-01

    Endophytic fungi, being a prolific source of bioactive secondary metabolites, are of great interest for natural product discovery. Isolation and partial characterization of endophytic fungi inhabiting the leaves and woody parts of Taxus fuana Nan Li & R.R. Mill. (Taxaceae) and evaluation of biological activity. Endophytic fungal isolates were identified by molecular analysis of internal transcribed spacer (ITS) regions of 18S rDNA. Extracts of the endophytic fungi cultured on potato dextrose agar and modified medium were evaluated using cancer chemoprevention bioassays [inhibition of TNF-α-induced NFκB, aromatase and inducible nitric oxide synthase (iNOS); induction of quinone reductase 1 (QR1)] and growth inhibition with MCF-7 cells. Nine of 15 fungal isolates were identified as belonging to Epicoccum, Mucor, Penicillium, Chaetomium, Paraconiothriym, Plectania or Trichoderma. Five of the 15 extracts inhibited NFκB activity (IC 50 values ranging between 0.18 and 17 μg/mL) and five inhibited iNOS (IC 50 values ranging between 0.32 and 12.9 μg/mL). In the aromatase assay, only two isolates mediated inhibition (IC 50 values 12.2 and 10.5 μg/mL). With QR1 induction, three extracts exhibited significant activity (concentrations to double activity values ranging between 0.20 and 5.5 μg/mL), and five extracts inhibited the growth of MCF-7 cells (IC 50 values ranging from 0.56 to 17.5 μg/mL). Six active cultures were derived from woody parts of the plant material. The endophytic fungi studied are capable of producing pharmacologically active natural compounds. In particular, isolates derived from the wood of Taxus fuana should be prioritized for the isolation and characterization of bioactive constituents.

  5. Cancer Chemoprevention and Piperine: Molecular Mechanisms and Therapeutic Opportunities

    Directory of Open Access Journals (Sweden)

    Rafiq A. Rather

    2018-02-01

    Full Text Available Cancer is a genetic disease characterized by unregulated growth and dissemination of malignantly transformed neoplastic cells. The process of cancer development goes through several stages of biochemical and genetic alterations in a target cell. Several dietary alkaloids have been found to inhibit the molecular events and signaling pathways associated with various stages of cancer development and therefore are useful in cancer chemoprevention. Cancer chemoprevention has long been recognized as an important prophylactic strategy to reduce the burden of cancer on health care system. Cancer chemoprevention assumes the use of one or more pharmacologically active agents to block, suppress, prevent, or reverse the development of invasive cancer. Piperine is an active alkaloid with an excellent spectrum of therapeutic activities such as anti-oxidant, anti-inflammatory, immunomodulatory, anti-asthmatic, anti-convulsant, anti-mutagenic, antimycobacterial, anti-amoebic, and anti-cancer activities. In this article, we made an attempt to sum up the current knowledge on piperine that supports the chemopreventive potential of this dietary phytochemical. Many mechanisms have been purported to understand the chemopreventive action of piperine. Piperine has been reported to inhibit the proliferation and survival of many types of cancer cells through its influence on activation of apoptotic signaling and inhibition of cell cycle progression. Piperine is known to affect cancer cells in variety of other ways such as influencing the redox homeostasis, inhibiting cancer stem cell (CSC self-renewal and modulation of ER stress and autophagy. Piperine can modify activity of many enzymes and transcription factors to inhibit invasion, metastasis, and angiogenesis. Piperine is a potent inhibitor of p-glycoprotein (P-gp and has a significant effect on the drug metabolizing enzyme (DME system. Because of its inhibitory influence on P-gp activity, piperine can reverse

  6. The natural chemopreventive agent sulforaphane inhibits STAT5 activity.

    Directory of Open Access Journals (Sweden)

    Sophia Pinz

    Full Text Available Signal transducer and activator of transcription STAT5 is an essential mediator of cytokine, growth factor and hormone signaling. While its activity is tightly regulated in normal cells, its constitutive activation directly contributes to oncogenesis and is associated to a number of hematological and solid tumor cancers. We previously showed that deacetylase inhibitors can inhibit STAT5 transcriptional activity. We now investigated whether the dietary chemopreventive agent sulforaphane, known for its activity as deacetylase inhibitor, might also inhibit STAT5 activity and thus could act as a chemopreventive agent in STAT5-associated cancers. We describe here sulforaphane (SFN as a novel STAT5 inhibitor. We showed that SFN, like the deacetylase inhibitor trichostatin A (TSA, can inhibit expression of STAT5 target genes in the B cell line Ba/F3, as well as in its transformed counterpart Ba/F3-1*6 and in the human leukemic cell line K562 both of which express a constitutively active form of STAT5. Similarly to TSA, SFN does not alter STAT5 initial activation by phosphorylation or binding to the promoter of specific target genes, in favor of a downstream transcriptional inhibitory effect. Chromatin immunoprecipitation assays revealed that, in contrast to TSA however, SFN only partially impaired the recruitment of RNA polymerase II at STAT5 target genes and did not alter histone H3 and H4 acetylation, suggesting an inhibitory mechanism distinct from that of TSA. Altogether, our data revealed that the natural compound sulforaphane can inhibit STAT5 downstream activity, and as such represents an attractive cancer chemoprotective agent targeting the STAT5 signaling pathway.

  7. Ellagitannins in Cancer Chemoprevention and Therapy

    Directory of Open Access Journals (Sweden)

    Tariq Ismail

    2016-05-01

    Full Text Available It is universally accepted that diets rich in fruit and vegetables lead to reduction in the risk of common forms of cancer and are useful in cancer prevention. Indeed edible vegetables and fruits contain a wide variety of phytochemicals with proven antioxidant, anti-carcinogenic, and chemopreventive activity; moreover, some of these phytochemicals also display direct antiproliferative activity towards tumor cells, with the additional advantage of high tolerability and low toxicity. The most important dietary phytochemicals are isothiocyanates, ellagitannins (ET, polyphenols, indoles, flavonoids, retinoids, tocopherols. Among this very wide panel of compounds, ET represent an important class of phytochemicals which are being increasingly investigated for their chemopreventive and anticancer activities. This article reviews the chemistry, the dietary sources, the pharmacokinetics, the evidence on chemopreventive efficacy and the anticancer activity of ET with regard to the most sensitive tumors, as well as the mechanisms underlying their clinically-valuable properties.

  8. Cactus pear: a natural product in cancer chemoprevention

    Directory of Open Access Journals (Sweden)

    Wang Jian

    2005-09-01

    Full Text Available Abstract Background Cancer chemoprevention is a new approach in cancer prevention, in which chemical agents are used to prevent cancer in normal and/or high-risk populations. Although chemoprevention has shown promise in some epithelial cancers, currently available preventive agents are limited and the agents are costly, generally with side effects. Natural products, such as grape seed, green tea, and certain herbs have demonstrated anti-cancer effects. To find a natural product that can be used in chemoprevention of cancer, we tested Arizona cactus fruit solution, the aqueous extracts of cactus pear, for its anti-cancer effects in cultured cells and in an animal model. Method Aqueous extracts of cactus pear were used to treat immortalized ovarian and cervical epithelial cells, as well as ovarian, cervical, and bladder cancer cells. Aqueous extracts of cactus pear were used at six concentrations (0, 0.5, 1, 5, 10 or 25% to treat cells for 1, 3, or 5 days. Growth inhibition, apoptosis induction, and cell cycle changes were analyzed in the cultured cells; the suppression of tumor growth in nude mice was evaluated and compared with the effect of a synthetic retinoid N-(4-hydroxyphernyl retinamide (4-HPR, which is currently used as a chemoprevention agent. Immunohistochemistry staining of tissue samples from animal tumors was performed to examine the gene expression. Results Cells exposed to cactus pear extracts had a significant increase in apoptosis and growth inhibition in both immortalized epithelial cells and cancer cells in a dose- and time-dependent manner. It also affected cell cycle of cancer cells by increasing G1 and decreasing G2 and S phases. Both 4-HPR and cactus pear extracts significantly suppressed tumor growth in nude mice, increased annexin IV expression, and decreased VEGF expression. Conclusion Arizona cactus pear extracts effectively inhibited cell growth in several different immortalized and cancer cell cultures, suppressed

  9. Cohorts with familial disposition for colon cancers in chemoprevention trials.

    Science.gov (United States)

    Burt, R W

    1996-01-01

    Colon cancer provides an attractive setting for chemoprevention trials because of the frequency and variation of familial predisposition that is observed in this malignancy. Additionally, the adenomatous polyp, the precursor of colon cancer, is a valuable intermediate marker for judging the effectiveness of candidate chemopreventive agents. Inherited colon cancer susceptibility varies from mild to severe. Conditions with extreme susceptibility include the autosomal dominantly inherited syndromes of familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC). These are highly penetrant syndromes with extreme cancer risk. FAP arises from mutations of the APC gene and HNPCC from mutations of the mismatch repair genes. Specific and individual genetic diagnosis is now possible in both syndromes, thus allowing identification of genetically affected individuals for chemoprevention trials. FAP accounts for less than 1% of colon cancers, while HNPCC may be present in up to 5% of cases. Familial clustering is common in the remainder of cases, which are often referred to as sporadic, but probably arise in part from inherited susceptibility. Epidemiologic studies have shown that first-degree relatives have a two- to four-fold increased risk of acquiring colon cancer compared to the general population. Ten percent of individuals in the U.S. have a first-degree with colon cancer. This clinically identifiable higher risk group thus constitutes a large potential cohort for chemoprevention trials. The common familial cases of colon cancer can be further stratified by severity. A relative diagnosed under the age of 50 or two first-degree relatives affected with colon cancer confers an even greater risk for this malignancy, estimated to be four to six times that of the general population. Adenomatous polyps also precede the development of colon cancer in these categories, thereby providing a readily identifiable clinical endpoint to judge the

  10. Nigerian foodstuffs with prostate cancer chemopreventive polyphenols

    OpenAIRE

    Atawodi, Sunday Eneojo

    2011-01-01

    Dietary polyphenols are antioxidants that can scavenge biological free radicals, and chemoprevent diseases with biological oxidation as their main etiological factor. In this paper, we review our laboratory data vis-?-vis available literature on prostate cancer chemopreventive substances in Nigerian foodstuffs. Dacryodes edulis fruit, Moringa oleifera and Syzygium aromaticum contained prostate active polyphenols like ellagic acid, gallate, methylgallate, catechol, kaempferol quercetin and the...

  11. Use of nonsteroidal antiinflamatory drugs for chemoprevention of colon cancer

    Directory of Open Access Journals (Sweden)

    Milić Aleksandra

    2013-01-01

    Full Text Available Colorectal cancer is in the third most frequent cancer among malignant tumors of both sexes in developed countries. It is predominantly a disease of older persons and occurs mostly after the age of 60. Although the etiology of colon cancer is unknown, it is assumed to arise as a result of unclear and complex interactions between genetic and environmental factors. The main element in the etiology of colorectal cancer is the process of genetic changes in epithelial cells of colon mucosa. It is believed that specific epidemiological factors such as stress, hypoxia, reduced intake of glucose and other nutrients, a hereditary predisposition to mutagenic effects, the meat in the diet, bile acids, reduced intake of minerals and vitamins as well as changes in pH of feces lead to initiation of the process of carcinogenesis in mucosa of the colon. Cancer chemoprevention is defined as the use of chemical agents in order to block, prevent or delay the reversal development or progress of cancer. It is believed that chemoprevention is a key component of cancer control, and numerous studies indicate potential role of NSAIDs in chemoprevention of colon cancer.

  12. Oral Carcinogenesis and Oral Cancer Chemoprevention: A Review

    Directory of Open Access Journals (Sweden)

    Takuji Tanaka

    2011-01-01

    Full Text Available Oral cancer is one of the major global threats to public health. The development of oral cancer is a tobacco-related multistep and multifocal process involving field cancerization and carcinogenesis. The rationale for molecular-targeted prevention of oral cancer is promising. Biomarkers of genomic instability, including aneuploidy and allelic imbalance, are possible to measure the cancer risk of oral premalignancies. Understanding of the biology of oral carcinogenesis will yield important advances for detecting high-risk patients, monitoring preventive interventions, and assessing cancer risk and pharmacogenomics. In addition, novel chemopreventive agents based on molecular mechanisms and targets against oral cancers will be derived from studies using appropriate animal carcinogenesis models. New approaches, such as molecular-targeted agents and agent combinations in high-risk oral individuals, are undoubtedly needed to reduce the devastating worldwide consequences of oral malignancy.

  13. Chemoprevention of prostate cancer with nutrients and supplements

    Directory of Open Access Journals (Sweden)

    Van Poppel H

    2011-04-01

    Full Text Available Hendrik Van Poppel1, Bertrand Tombal21Department of Urology, University Hospital, KU Leuven, Leuven, Belgium; 2Service d’Urologie, Cliniques Universtaires Saint Luc, Brussels, BelgiumAbstract: As the adult population is increasing, prostate cancer (PCa will become a considerable health problem in the next millennium. This has raised public interest in potential chemoprevention of this disease. As PCa is extremely common and generally slow to progress it is regarded as an ideal candidate for chemoprevention. At present, the 5 alpha-reductase inhibitors finasteride and dutasteride have been identified as preventive agents. This review describes whether selenium, alpha-tocopherol, isoflavones, lycopene green tea polyphenols, calcium, and resveratrol may be useful for decreasing the risk of PCa in men. Although encouraging results are present, some studies show negative results. Differences in study design, sample size, dose administered, and/or concentrations achieved in the body may be the reason for these inconsistencies. Today, chemopreventive agents may be appropriate for high-risk patients like those with high-grade prostatic intraepithelial neoplasia and other high-risk groups such as patients with elevated prostate specific antigen (PSA and negative biopsy, rapid PSA velocity, and with a family history of PCa. Although larger randomized controlled studies are needed and epidemiologic evidence should be placed in a clinical context, physicians must be aware of these preventive opportunities in PCa care. Combinations of chemopreventive agents should be carefully investigated because mechanisms of action may be additive or synergistic.Keywords: alpha-tocopherol, chemoprevention, isoflavones, lycopene, polyphenols, prostate cancer, selenium

  14. Green tea polyphenols for prostate cancer chemoprevention: A translational perspective

    Science.gov (United States)

    Johnson, J.J.; Bailey, H.H.; Mukhtar, H.

    2009-01-01

    Every year nearly 200,000 men in the United States are diagnosed with prostate cancer (PCa), and another 29,000 men succumb to the disease. Within certain regions of the world population based studies have identified a possible role for green tea in the prevention of certain cancers, especially PCa. One constituent in particular, epigallocatechin-3-gallate also known as EGCG has been shown in cell culture models to decrease cell viability and promote apoptosis in multiple cancer cell lines including PCa with no effect on non-cancerous cell lines. In addition, animal models have consistently shown that standardized green tea polyphenols when administered in drinking water delay the development and progression of PCa. Altogether, three clinical trials have been performed in PCa patients and suggest that green tea may have a distinct role as a chemopreventive agent. This review will present the available data for standardized green tea polyphenols in regard to PCa chemoprevention that will include epidemiological, mechanism based studies, safety, pharmacokinetics, and applicable clinical trials. The data that has been collected so far suggests that green tea may be a promising agent for PCa chemoprevention and further clinical trials of participants at risk of PCa or early stage PCa are warranted. PMID:19959000

  15. Design, synthesis and experimental validation of novel potential chemopreventive agents using random forest and support vector machine binary classifiers.

    Science.gov (United States)

    Sprague, Brienne; Shi, Qian; Kim, Marlene T; Zhang, Liying; Sedykh, Alexander; Ichiishi, Eiichiro; Tokuda, Harukuni; Lee, Kuo-Hsiung; Zhu, Hao

    2014-06-01

    Compared to the current knowledge on cancer chemotherapeutic agents, only limited information is available on the ability of organic compounds, such as drugs and/or natural products, to prevent or delay the onset of cancer. In order to evaluate chemical chemopreventive potentials and design novel chemopreventive agents with low to no toxicity, we developed predictive computational models for chemopreventive agents in this study. First, we curated a database containing over 400 organic compounds with known chemoprevention activities. Based on this database, various random forest and support vector machine binary classifiers were developed. All of the resulting models were validated by cross validation procedures. Then, the validated models were applied to virtually screen a chemical library containing around 23,000 natural products and derivatives. We selected a list of 148 novel chemopreventive compounds based on the consensus prediction of all validated models. We further analyzed the predicted active compounds by their ease of organic synthesis. Finally, 18 compounds were synthesized and experimentally validated for their chemopreventive activity. The experimental validation results paralleled the cross validation results, demonstrating the utility of the developed models. The predictive models developed in this study can be applied to virtually screen other chemical libraries to identify novel lead compounds for the chemoprevention of cancers.

  16. Design, synthesis and experimental validation of novel potential chemopreventive agents using random forest and support vector machine binary classifiers

    Science.gov (United States)

    Sprague, Brienne; Shi, Qian; Kim, Marlene T.; Zhang, Liying; Sedykh, Alexander; Ichiishi, Eiichiro; Tokuda, Harukuni; Lee, Kuo-Hsiung; Zhu, Hao

    2014-06-01

    Compared to the current knowledge on cancer chemotherapeutic agents, only limited information is available on the ability of organic compounds, such as drugs and/or natural products, to prevent or delay the onset of cancer. In order to evaluate chemical chemopreventive potentials and design novel chemopreventive agents with low to no toxicity, we developed predictive computational models for chemopreventive agents in this study. First, we curated a database containing over 400 organic compounds with known chemoprevention activities. Based on this database, various random forest and support vector machine binary classifiers were developed. All of the resulting models were validated by cross validation procedures. Then, the validated models were applied to virtually screen a chemical library containing around 23,000 natural products and derivatives. We selected a list of 148 novel chemopreventive compounds based on the consensus prediction of all validated models. We further analyzed the predicted active compounds by their ease of organic synthesis. Finally, 18 compounds were synthesized and experimentally validated for their chemopreventive activity. The experimental validation results paralleled the cross validation results, demonstrating the utility of the developed models. The predictive models developed in this study can be applied to virtually screen other chemical libraries to identify novel lead compounds for the chemoprevention of cancers.

  17. Biomarkers and their use in cervical cancer chemoprevention.

    Science.gov (United States)

    Vlastos, Anne Thérèse; Schottenfeld, David; Follen, Michele

    2003-06-01

    Cervical cancer chemoprevention agents under study include diet and micronutrients (particularly beta-carotene, folate, and vitamins A, C, and E); medications such as retinoids (retinyl acetate gel, all-trans-retinoic acid, and 4-hydroxyphenylretinamide) that are chemically related to micronutrients; and other chemopreventives meant to affect the carcinogenic process at the cellular level, including such polyamine synthesis inhibitors as alpha-difluoromethylornithine. Agents become reasonable candidates for study when they have a biologic rationale, they are of low toxicity, and they can be taken for a long period of time. Since the human papillomavirus (HPV) is the major etiologic agent, the medication should show activity against HPV-positive preinvasive and invasive cell lines. The medication needs to be of low toxicity because it may be taken for long periods of time and less toxicity is tolerated in the precancerous setting. Until 1995, none of the studies used surrogate end point biomarkers (SEBs), relying instead on histologic and colposcopic regression as end points. All studies typically included subjects with cervical intraepithelial neoplasia. Conclusions to be drawn from these studies include the following: Though micronutrients are logical candidates for chemoprevention, they haven't worked consistently, and the reasons remain unclear. Furthermore, SEBs need to be validated in phase I trials. Finally, a better understanding of the role of HPV needs elucidation, including an understanding of the relationship of the medication to HPV status and of the immunobiology of HPV throughout the trial.

  18. Ginseng Metabolites on Cancer Chemoprevention: An Angiogenesis Link?

    Directory of Open Access Journals (Sweden)

    Chong-Zhi Wang

    2015-09-01

    Full Text Available Cancer is a leading cause of death in the United States. Angiogenesis inhibitors have been introduced for the treatment of cancer. Based on the fact that many anticancer agents have been developed from botanical sources, there is a significant untapped resource to be found in natural products. American ginseng is a commonly used herbal medicine in the U.S., which possesses antioxidant properties. After oral ingestion, natural ginseng saponins are biotransformed to their metabolites by the enteric microbiome before being absorbed. The major metabolites, ginsenoside Rg3 and compound K, showed significant potent anticancer activity compared to that of their parent ginsenosides Rb1, Rc, and Rd. In this review, the molecular mechanisms of ginseng metabolites on cancer chemoprevention, especially apoptosis and angiogenic inhibition, are discussed. Ginseng gut microbiome metabolites showed significant anti-angiogenic effects on pulmonary, gastric and ovarian cancers. This review suggests that in addition to the chemopreventive effects of ginseng compounds, as angiogenic inhibitors, ginsenoside metabolites could be used in combination with other cancer chemotherapeutic agents in cancer management.

  19. Guggulsterone for Chemoprevention of Cancer.

    Science.gov (United States)

    Shishodia, Shishir; Azu, Nkem; Rosenzweig, Jason A; Jackson, Desiree A

    2016-01-01

    Guggulsterone [4, 17(20)-pregnadiene-3, 16-dione] is a plant sterol derived from the gum resin of the tree Commiphora wightii. The gum resin of the guggul tree has been used in traditional medicine for centuries to treat obesity, liver disorders, internal tumors, malignant sores, ulcers, urinary complaints, intestinal worms, leucoderma, sinus, edema and sudden paralytic seizures. Guggulsterone has been shown to modulate the nuclear receptors, farnesoid X receptor, pregnane X receptor, CYP 2b10 gene expression, and the bile salt export pump for cholesterol elimination. Recent research indicates that the active components of gum guggul, E- and Zguggulsterone have the potential to both prevent and treat cancers. Guggulsterone inhibits the growth of a wide variety of tumor cells and induces apoptosis through down regulation of antiapoptotic gene products (IAP1, xIAP, Bfl-1/A1, Bcl-2, cFLIP, and survivin), modulation of cell cycle proteins (cyclin D1 and c-Myc), activation of caspases, inhibition of Akt, and activation of JNK. Guggulsterone modulates the expression of gene products involved in metastasis (MMP-9, COX-2, and VEGF) of tumor cells. Guggulsterone mediates gene expression through the modulation of several transcription factors, including NF-κB, STAT3, C/EBPα, androgen receptor, and glucocorticoid receptors. This review describes the anti-cancer properties, molecular targets, and the apoptotic effects of guggulsterone.

  20. Xanthones from Mangosteen Extracts as Natural Chemopreventive Agents: Potential Anticancer Drugs

    Science.gov (United States)

    Shan, T.; Ma, Q.; Guo, K.; Liu, J.; Li, W.; Wang, F.; Wu, E.

    2011-01-01

    Despite decades of research, the treatment and management of malignant tumors still remain a formidable challenge for public health. New strategies for cancer treatment are being developed, and one of the most promising treatment strategies involves the application of chemopreventive agents. The search for novel and effective cancer chemopreventive agents has led to the identification of various naturally occurring compounds. Xanthones, from the pericarp, whole fruit, heartwood, and leaf of mangosteen (Garcinia mangostana Linn., GML), are known to possess a wide spectrum of pharmacologic properties, including anti-oxidant, anti-tumor, anti-allergic, anti-inflammatory, anti-bacterial, anti-fungal, and anti-viral activities. The potential chemopreventive and chemotherapeutic activities of xanthones have been demonstrated in different stages of carcinogenesis (initiation, promotion, and progression) and are known to control cell division and growth, apoptosis, inflammation, and metastasis. Multiple lines of evidence from numerous in vitro and in vivo studies have confirmed that xanthones inhibit proliferation of a wide range of human tumor cell types by modulating various targets and signaling transduction pathways. Here we provide a concise and comprehensive review of preclinical data and assess the observed anticancer effects of xanthones, supporting its remarkable potential as an anticancer agent. PMID:21902651

  1. Resveratrol in human cancer chemoprevention--choosing the 'right' dose.

    Science.gov (United States)

    Scott, Edwina; Steward, William P; Gescher, Andreas J; Brown, Karen

    2012-01-01

    There is now robust preclinical evidence to suggest that resveratrol possesses cancer chemopreventive properties. A series of clinical pilot studies has provided insights into its pharmacokinetics, and data on its human antineoplastic pharmacodynamics start to emerge. It is likely that resveratrol will be developed further in the clinic as a putative cancer chemopreventive agent. The question that remains unresolved is: What is the most suitable dose of resveratrol for effective cancer preventive intervention? Mechanistic studies in cells in vitro have almost invariably used concentrations of resveratrol in the 10(-5) to 10(-4)  M range, which is much higher than those which can be achieved in the human biophase after consumption of doses up to 1 g. Many of the preclinical efficacy studies in rodent models of carcinogenesis have employed doses which are dramatically above those which can be ingested with the diet. New experimental paradigms need to be used to obtain information on pharmacological changes elicited by resveratrol when present at very low concentrations or when administered at dietary-relevant doses. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Aspirin Metabolomics in Colorectal Cancer Chemoprevention | Division of Cancer Prevention

    Science.gov (United States)

    DESCRIPTION (provided by applicant): Substantial evidence supports the effectiveness of aspirin for cancer chemoprevention in addition to its well-established role in cardiovascular protection. In recent meta-analyses of randomized controlled trials in humans, daily aspirin use reduced incidence, metastasis and mortality from several common types of cancer, especially colorectal cancer. The mechanism(s) by which aspirin exerts an anticancer benefit is uncertain; numerous effects have been described involving both cyclooxygenase-dependent and -independent pathways. |

  3. Chemoprevention of prostate cancer: Natural compounds, antiandrogens, and antioxidants - In vivo evidence

    Directory of Open Access Journals (Sweden)

    Nur Özten-Kandas

    2011-01-01

    Full Text Available Prostate cancer is the leading non-skin malignancy detected in US males and the second cause of death due to male cancer, in the US. Interventions with drugs or diet supplements that slow down the growth and progression of prostate cancer are potentially very effective in reducing the burden of prostate cancer, particularly if these treatments also prevent the de novo development of new prostatic malignancies. Challenges to identify efficacious agents and develop them for chemopreventive application in men at risk for prostate cancer have included uncertainty about which preclinical models have the ability to predict efficacy in men and lack of consensus about which early phase clinical trial designs are the most appropriate and cost-effective to test promising agents. Efficacy studies in animal models have identified several agents with potential chemopreventive activity against prostate cancer, but few of these findings have been translated into clinical trials. This article identifies some of the major issues associated with prostate cancer chemoprevention research and summarizes the most significant current results from animal efficacy studies and human clinical prevention trials. This summary focuses on: (1 Naturally occurring agents and compounds derived from such agents, including green tea and its constituents, silibinin and milk thistle, and genistein and soy, (2 chemoprevention drugs including agents interfering with androgen action, and (3 antioxidants such as selenium, vitamin E, and lycopene. The general lack of activity of antioxidants is discussed, followed by considerations about translation of preclinical chemoprevention efficacy data, focusing on dose, form, bioavailability, and timing of administration of the agent, as well as discussion of study design of clinical trials and the predictive ability of preclinical models.

  4. Hedera nepalensis K. Koch: A Novel Source of Natural Cancer Chemopreventive and Anticancerous Compounds.

    Science.gov (United States)

    Jafri, Laila; Saleem, Samreen; Kondrytuk, Tamara P; Haq, Ihsan-ul; Ullah, Nazif; Pezzuto, John M; Mirza, Bushra

    2016-03-01

    Traditional medicinal plants are often used for both the prevention and the treatment of local diseases. Taking into consideration the medicinal importance of Hedera nepalensis within local Pakistani traditions, the present study was undertaken to analyze the in vitro cancer chemopreventive and cytotoxic properties of the plant. The in vitro cancer chemopreventive testing was performed using nitrite assay, NFκB assay, aromatase assay, and quinone reductase 1 (QR1) assay. The cytotoxic potential was evaluated on three cancer-cell lines: MCF-7, MDA-MB-231, and HeLa using sulforhodamine B (SRB) assay. The results of cancer chemopreventive assays show that n-hexane and ethyl acetate fractions of tested plant have promising cancer chemopreventive potential. Lupeol isolated from n-hexane as well as ethyl acetate fraction showed lowest IC50 (0.20 ± 1.9 μM) in NFκB assay. Crude extract and its fractions inhibited the growth of three cancer cell lines by more than 60%, IC50 value of lupeol varied from 2.32 to 10.2 μM. HPLC-DAD-based quantification of lupeol in different plant tissues demonstrated that leaves of H. nepalensis are a rich source of lupeol (0.196 mg/100 mg dry weight). Our data have shown that H. nepalensis harbors cancer chemopreventive and cytotoxic agents. Copyright © 2015 John Wiley & Sons, Ltd.

  5. Cancer chemoprevention by dietary phytochemicals: Epidemiological evidence.

    Science.gov (United States)

    Baena Ruiz, Raúl; Salinas Hernández, Pedro

    2016-12-01

    In recent years, natural compounds called "phytochemicals", which are present in fruits, vegetables, and plants, have received special attention due to their potential to interfere with tumour formation and development. Many of these phytochemicals are being used in chemoprevention strategies. However, the scientific evidence regarding the modification of cancer risk continues to be debated. The aim of this paper is to review the current scientific evidence and the most relevant epidemiological studies regarding the consumption or use of phytochemicals and their effects on the incidence of cancer. A search for relevant articles was conducted in EMBASE and PubMed-NCBI through to May 2016 to identify potential interactions between the consumption or use of phytochemicals and cancer risk. The use or consumption of carotenoids, such as lycopene, alpha-carotene, and betacarotene, leads to a reduction in the risk of cancer, such as breast and prostate tumours. For breast cancer, beta-carotene even reduces the risk of recurrence. The use or consumption of soybean isoflavones has led to a reduction in the risk of lung, prostate, colon (in women only), and breast cancers, although this has depended on menopausal and oestrogen receptor status. The use or consumption of isothiocyanates and indole-3-carbinol also seems to reduce the risk of cancer, such as breast, stomach, colorectal, or prostate tumours. The adoption of a diet rich in phytochemicals is associated with a modification of cancer risk. However, the scientific data supporting its use come mainly from in vitro and in vivo studies (especially in animal models). The epidemiological evidence is inconclusive for many of these phytochemicals, so further studies are needed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Anticancer and cancer chemopreventive potential of grape seed extract and other grape-based products.

    Science.gov (United States)

    Kaur, Manjinder; Agarwal, Chapla; Agarwal, Rajesh

    2009-09-01

    With emerging trends in the incidence of cancer of various organ sites, additional approaches are needed to control human malignancies. Intervention or prevention of cancer by dietary constituents, a strategy defined as chemoprevention, holds great promise in our conquest to control cancer, because it can be implemented on a broader population base with less economic burden. Consistent with this, several epidemiological studies have shown that populations that consume diets rich in fruits and vegetables have an overall lower cancer incidence. Based on these encouraging observations, research efforts from across the globe have focused on identifying, characterizing, and providing scientific basis to the efficacy of various phytonutrients in an effort to develop effective strategy to control various human malignancies. Cancer induction, growth, and progression are multi-step events and numerous studies have demonstrated that various dietary agents interfere with these stages of cancer, thus blocking malignancy. Fruits and vegetables represent untapped reservoir of various nutritive and nonnutritive phytochemicals with potential cancer chemopreventive activity. Grapes and grape-based products are one such class of dietary products that have shown cancer chemopreventive potential and are also known to improve overall human health. This review focuses on recent advancements in cancer chemopreventive and anticancer efficacy of grape seed extract and other grape-based products. Overall, completed studies from various scientific groups conclude that both grapes and grape-based products are excellent sources of various anticancer agents and their regular consumption should thus be beneficial to the general population.

  7. Mode of action of aspirin as a chemopreventive agent.

    Science.gov (United States)

    Dovizio, Melania; Bruno, Annalisa; Tacconelli, Stefania; Patrignani, Paola

    2013-01-01

    Aspirin taken for several years at doses of at least 75 mg daily reduced long-term incidence and mortality due to colorectal cancer. The finding of aspirin benefit at low-doses given once daily, used for cardioprevention, locates the antiplatelet effect of aspirin at the center of its antitumor efficacy. In fact, at low-doses, aspirin acts mainly by an irreversible inactivation of platelet cyclooxygenase (COX)-1 in the presystemic circulation, which translates into a long-lasting inhibition of platelet function. Given the short half-life of aspirin in the human circulation(approximately 20 min) and the capacity of nucleated cells to resynthesize the acetylated COX-isozyme(s), it seems unlikely that a nucleated cell could be the target of aspirin chemoprevention. These findings convincingly suggest that colorectal cancer and atherothrombosis may share a common mechanism of disease, i.e. platelet activation in response to epithelial(in tumorigenesis) and endothelial(in tumorigenesis and atherothrombosis) injury. Activated platelets may also enhance the metastatic potential of cancer cells (through a direct interaction and/or the release of soluble mediators or exosomes) at least in part by inducing the overexpression of COX-2. COX-independent mechanisms of aspirin, such as the inhibition of NF-kB signaling and Wnt/β-catenin signaling and the acetylation of extra-COX proteins, have been suggested to play a role in its chemopreventive effects. However, their relevance remains to be demonstrated in vivo at clinical doses.

  8. Nanoencapsulation of pomegranate bioactive compounds for breast cancer chemoprevention

    Science.gov (United States)

    Shirode, Amit B; Bharali, Dhruba J; Nallanthighal, Sameera; Coon, Justin K; Mousa, Shaker A; Reliene, Ramune

    2015-01-01

    Pomegranate polyphenols are potent antioxidants and chemopreventive agents but have low bioavailability and a short half-life. For example, punicalagin (PU), the major polyphenol in pomegranates, is not absorbed in its intact form but is hydrolyzed to ellagic acid (EA) moieties and rapidly metabolized into short-lived metabolites of EA. We hypothesized that encapsulation of pomegranate polyphenols into biodegradable sustained release nanoparticles (NPs) may circumvent these limitations. We describe here the development, characterization, and bioactivity assessment of novel formulations of poly(D,L-lactic-co-glycolic acid)–poly(ethylene glycol) (PLGA–PEG) NPs loaded with pomegranate extract (PE) or individual polyphenols such as PU or EA. Monodispersed, spherical 150–200 nm average diameter NPs were prepared by the double emulsion–solvent evaporation method. Uptake of Alexa Fluor-488-labeled NPs was evaluated in MCF-7 breast cancer cells over a 24-hour time course. Confocal fluorescent microscopy revealed that PLGA–PEG NPs were efficiently taken up, and the uptake reached the maximum at 24 hours. In addition, we examined the antiproliferative effects of PE-, PU-, and/or EA-loaded NPs in MCF-7 and Hs578T breast cancer cells. We found that PE, PU, and EA nanoprototypes had a 2- to 12-fold enhanced effect on cell growth inhibition compared to their free counterparts, while void NPs did not affect cell growth. PU-NPs were the most potent nanoprototype of pomegranates. Thus, PU may be the polyphenol of choice for further chemoprevention studies with pomegranate nanoprototypes. These data demonstrate that nanotechnology-enabled delivery of pomegranate polyphenols enhances their anticancer effects in breast cancer cells. Thus, pomegranate polyphenols are promising agents for nanochemoprevention of breast cancer. PMID:25624761

  9. Nanoencapsulation of pomegranate bioactive compounds for breast cancer chemoprevention.

    Science.gov (United States)

    Shirode, Amit B; Bharali, Dhruba J; Nallanthighal, Sameera; Coon, Justin K; Mousa, Shaker A; Reliene, Ramune

    2015-01-01

    Pomegranate polyphenols are potent antioxidants and chemopreventive agents but have low bioavailability and a short half-life. For example, punicalagin (PU), the major polyphenol in pomegranates, is not absorbed in its intact form but is hydrolyzed to ellagic acid (EA) moieties and rapidly metabolized into short-lived metabolites of EA. We hypothesized that encapsulation of pomegranate polyphenols into biodegradable sustained release nanoparticles (NPs) may circumvent these limitations. We describe here the development, characterization, and bioactivity assessment of novel formulations of poly(D,L-lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) NPs loaded with pomegranate extract (PE) or individual polyphenols such as PU or EA. Monodispersed, spherical 150-200 nm average diameter NPs were prepared by the double emulsion-solvent evaporation method. Uptake of Alexa Fluor-488-labeled NPs was evaluated in MCF-7 breast cancer cells over a 24-hour time course. Confocal fluorescent microscopy revealed that PLGA-PEG NPs were efficiently taken up, and the uptake reached the maximum at 24 hours. In addition, we examined the antiproliferative effects of PE-, PU-, and/or EA-loaded NPs in MCF-7 and Hs578T breast cancer cells. We found that PE, PU, and EA nanoprototypes had a 2- to 12-fold enhanced effect on cell growth inhibition compared to their free counterparts, while void NPs did not affect cell growth. PU-NPs were the most potent nanoprototype of pomegranates. Thus, PU may be the polyphenol of choice for further chemoprevention studies with pomegranate nanoprototypes. These data demonstrate that nanotechnology-enabled delivery of pomegranate polyphenols enhances their anticancer effects in breast cancer cells. Thus, pomegranate polyphenols are promising agents for nanochemoprevention of breast cancer.

  10. Molecular mechanisms of chemopreventive phytochemicals against gastroenterological cancer development

    Science.gov (United States)

    Chung, Min-Yu; Lim, Tae Gyu; Lee, Ki Won

    2013-01-01

    Cancer is one of the leading causes of death worldwide. Commonly used cancer treatments, including chemotherapy and radiation therapy, often have side effects and a complete cure is sometimes impossible. Therefore, prevention, suppression, and/or delaying the onset of the disease are important. The onset of gastroenterological cancers is closely associated with an individual’s lifestyle. Thus, changing lifestyle, specifically the consumption of fruits and vegetables, can help to protect against the development of gastroenterological cancers. In particular, naturally occurring bioactive compounds, including curcumin, resveratrol, isothiocyanates, (-)-epigallocatechin gallate and sulforaphane, are regarded as promising chemopreventive agents. Hence, regular consumption of these natural bioactive compounds found in foods can contribute to prevention, suppression, and/or delay of gastroenterological cancer development. In this review, we will summarize natural phytochemicals possessing potential antioxidant and/or anti-inflammatory and anti-carcinogenic activities, which are exerted by regulating or targeting specific molecules against gastroenterological cancers, including esophageal, gastric and colon cancers. PMID:23467658

  11. Chemopreventive effects of natural dietary compounds on cancer development.

    Science.gov (United States)

    Pan, Min-Hsiung; Ho, Chi-Tang

    2008-11-01

    Chemoprevention, a relatively new and promising strategy to prevent cancer, is defined as the use of natural dietary compounds and/or synthetic substances to block, inhibit, reverse, or retard the process of carcinogenesis. The chemopreventive effects elicited by these natural dietary compounds are believed to include antioxidative, anti-inflammatory activity, induction of phase II enzymes, apoptosis, and cell cycle arrest. Many mechanisms have been shown to account for the anticarcinogenic actions of natural dietary compounds; attention has recently been focused on intracellular-signaling cascades as common molecular targets for various chemopreventive natural dietary compounds. In this critical review, we will summarize current knowledge on natural dietary compounds that act through the signaling pathways and modulate gene expression to induce detoxifying enzymes, programmed cell death, anti-inflammatory, and anti-proliferative effects, thus providing evidence for these substances in cancer chemopreventive action (128 references).

  12. Sulforaphane, a cancer chemopreventive agent, induces pathways associated with membrane biosynthesis in response to tissue damage by aflatoxin B{sub 1}

    Energy Technology Data Exchange (ETDEWEB)

    Techapiesancharoenkij, Nirachara [Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Bangkok 10210 (Thailand); Fiala, Jeannette L.A. [Department of Biological Engineering and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Navasumrit, Panida [Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Bangkok 10210 (Thailand); Croy, Robert G.; Wogan, Gerald N. [Department of Biological Engineering and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Groopman, John D. [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205 (United States); Ruchirawat, Mathuros [Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Bangkok 10210 (Thailand); Essigmann, John M., E-mail: jessig@mit.edu [Department of Biological Engineering and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States)

    2015-01-01

    Aflatoxin B{sub 1} (AFB{sub 1}) is one of the major risk factors for liver cancer globally. A recent study showed that sulforaphane (SF), a potent inducer of phase II enzymes that occurs naturally in widely consumed vegetables, effectively induces hepatic glutathione S-transferases (GSTs) and reduces levels of hepatic AFB{sub 1}-DNA adducts in AFB{sub 1}-exposed Sprague Dawley rats. The present study characterized the effects of SF pre-treatment on global gene expression in the livers of similarly treated male rats. Combined treatment with AFB{sub 1} and SF caused reprogramming of a network of genes involved in signal transduction and transcription. Changes in gene regulation were observable 4 h after AFB{sub 1} administration in SF-pretreated animals and may reflect regeneration of cells in the wake of AFB{sub 1}-induced hepatotoxicity. At 24 h after AFB{sub 1} administration, significant induction of genes that play roles in cellular lipid metabolism and acetyl-CoA biosynthesis was detected in SF-pretreated AFB{sub 1}-dosed rats. Induction of this group of genes may indicate a metabolic shift toward glycolysis and fatty acid synthesis to generate and maintain pools of intermediate molecules required for tissue repair, cell growth and compensatory hepatic cell proliferation. Collectively, gene expression data from this study provide insights into molecular mechanisms underlying the protective effects of SF against AFB{sub 1} hepatotoxicity and hepatocarcinogenicity, in addition to the chemopreventive activity of this compound as a GST inducer. - Highlights: • This study revealed sulforaphane (SF)-deregulated gene sets in aflatoxin B{sub 1} (AFB{sub 1})-treated rat livers. • SF redirects biochemical networks toward lipid biosynthesis in AFB{sub 1}-dosed rats. • SF enhanced gene sets that would be expected to favor cell repair and regeneration.

  13. Prostate cancer chemoprevention in men of African descent: current state of the art and opportunities for future research.

    Science.gov (United States)

    Chornokur, Ganna; Kumar, Nagi B

    2013-08-01

    Prostate cancer is the most frequently diagnosed malignancy in men. However, African American/Black men are 60 % more likely to be diagnosed with and 2.4 times more likely to die from prostate cancer, compared to Non-Hispanic White men. Despite the increased burden of this malignancy, no evidence-based recommendation regarding prostate cancer screening exists for the high-risk population. Moreover, in addition to screening and detection, African American men may constitute a prime population for chemoprevention. Early detection and chemoprevention may thus represent an integral part of prostate cancer control in this population. Importantly, recent research has elucidated biological differences in the prostate tumors of African American compared to European American men. The latter may enable a more favorable response in African American men to specific chemopreventive agents that target relevant signal transduction pathways. Based on this evolving evidence, the aims of this review are threefold. First, we aim to summarize the biological differences that were reported in the prostate tumors of African American and European American men. Second, we will review the single- and multi-target chemopreventive agents placing specific emphasis on the pathways implicated in prostate carcinogenesis. And lastly, we will discuss the most promising nutraceutical chemopreventive compounds. Our review underscores the promise of chemoprevention in prostate cancer control, as well as provides justification for further investment in this filed to ultimately reduce prostate cancer morbidity and mortality in this high-risk population of African American men.

  14. Retinoids in the chemoprevention of non-melanoma skin cancers: why, when and how.

    Science.gov (United States)

    Bettoli, Vincenzo; Zauli, Stefania; Virgili, Anna

    2013-06-01

    The chemoprevention refers to the use of various types of chemical agents for preventing carcinogenic progression. Systemic retinoids are the most studied chemopreventive agents due to their capacity to regulate cell proliferation and their demonstrated efficacy in several clinical studies. The aim of the authors was to give precise indications regarding the use of the systemic retinoid in the chemoprevention of non-melanoma skin cancer (NMSC). The authors reviewed the literature found through a search to MEDLINE (from 2001 to December 2011). Both acitretin and isotretinoin are effective for the prevention of NMSC. Isotretinoin is preferred in xeroderma pigmentosum and nevoid basal cell carcinoma syndrome, whereas acitretin is more used in transplant recipients, psoriasis and severe sun damage. Despite numerous studies of the literature concerning retinoids in chemoprevention of NMSC, precise details of the type of retinoid to use, dosage and the duration of this preventive treatment and how to manage side effects in the case of long-lasting treatment are still not uniform and comparable. Moreover, neither guidelines nor approval by Food and Drug Administration exist to regulate the use of retinoids in chemoprevention.

  15. COX-independent mechanisms of cancer chemoprevention by anti-inflammatory drugs

    Directory of Open Access Journals (Sweden)

    Evrim eGurpinar

    2013-07-01

    Full Text Available Epidemiological and clinical studies suggest that non-steroidal anti-inflammatory drugs (NSAIDs, including cyclooxygenase (COX-2 selective inhibitors, reduce the risk of developing cancer. Experimental studies in human cancer cell lines and rodent models of carcinogenesis support these observations by providing strong evidence for the antineoplastic properties of NSAIDs. The involvement of COX-2 in tumorigenesis and its overexpression in various cancer tissues suggest that inhibition of COX-2 is responsible for the chemopreventive efficacy of these agents. However, the precise mechanisms by which NSAIDs exert their antiproliferative effects are still a matter of debate. Numerous other studies have shown that NSAIDs can act through COX-independent mechanisms. This review provides a detailed description of the major COX-independent molecular targets of NSAIDs and discusses how these targets may be involved in their anticancer effects. Toxicities resulting from COX inhibition and the suppression of prostaglandin synthesis preclude the long-term use of NSAIDs for cancer chemoprevention. Furthermore, chemopreventive efficacy is incomplete and treatment often leads to the development of resistance. Identification of alternative NSAID targets and elucidation of the biochemical processes by which they inhibit tumor growth could lead to the development of safer and more efficacious drugs for cancer chemoprevention.

  16. Chemoprevention of breast cancer by dietary compounds.

    Science.gov (United States)

    Vadodkar, Aditi S; Suman, Suman; Lakshmanaswamy, Rajkumar; Damodaran, Chendil

    2012-12-01

    Breast cancer is the leading cause of cancer-related deaths in women in the United States and many other countries. There is an immediate need for more effective and less toxic therapeutic and preventive strategies for many cancers, especially for breast cancer. Natural products are being tested with a hope of identifying novel potent molecules as anticancer agents. Phytochemicals and dietary compounds have been used for the treatment of various illnesses throughout history due to their safety, low toxicity, and general availability. Currently, many active phytochemicals are in clinical trials. Preclinical and clinical studies have indicated that daily consumption of dietary phytochemicals reduces the risk of several cancers. Phytochemicals can inhibit, delay, or reverse carcinogenesis by inducing detoxifying and antioxidant enzymes, by regulating inflammatory/proliferative signaling pathways, and by inducing apoptosis. This review article describes some of the potential natural cancer preventive compounds, along with a mechanistic discussion of their interactions with key cellular signal transduction pathways as well as their contribution to the suppression of breast cancer cell growth.

  17. Characterization of vitamin-cisplatin-loaded chitosan nano-particles for chemoprevention and cancer fatigue.

    Science.gov (United States)

    Othayoth, Rajath; Mathi, Pardhasaradhi; Bheemanapally, Khaggeswar; Kakarla, Lavanya; Botlagunta, Mahendran

    2015-01-01

    Vitamins have been shown to reduce chemotherapy-related fatigue (CRF) by conserving energy loss both during and after cancer treatment. However, it remains unknown whether this reduction of fatigue interferes with the cancer drugs or alters the effectiveness of these agents. The objective was to synthesize vitamin-cisplatin-loaded chitosan nano-particles for chemoprevention and cancer fatigue. Multi-vitamin (C, D3, and B12)-cisplatin composite nano-formulation called NanoCisVital (NCV) to overcome CRF. The interactions between vitamins and NCV were characterized using scanning electron microscopy (SEM), Fourier transform infrared (FT-IR) spectroscopy, and a particle size analyser. The chemo-preventive activity was performed by in vitro bio assays. SEM analysis showed spherical shape and the size is cancer properties of cisplatin.

  18. Chemopreventive potential of natural compounds in head and neck cancer

    OpenAIRE

    Rahman, Mohammad Aminur; Amin, A.R.M. Ruhul; Shin, Dong M.

    2010-01-01

    Head and neck squamous cell carcinoma (HNSCC) is one of the most fatal cancers world-wide. Despite advances in the management of HNSCC, the overall survival for patients has not improved significantly due to advanced stages at diagnosis, high recurrence rate after surgical removal, and second primary tumor development, which together underscore the importance of novel strategies for cancer prevention. Cancer chemoprevention, the use of natural or synthetic compounds to prevent, arrest, or rev...

  19. Role of saffron and its constituents on cancer chemoprevention

    Science.gov (United States)

    Zhang, Zhiyu; Wang, Chong-Zhi; Wen, Xiao-Dong; Shoyama, Yukihiro; Yuan, Chun-Su

    2014-01-01

    Context Cancer dramatically impacts human life expectancy and quality of life. Natural substances from vegetables, herbs and spices could be beneficial in the prevention or treatment of a variety of cancers. Crocus sativus, which has been used as a folk medicine for treating diseases for ages, showed obvious cancer chemoprevention potential. Objective This article focuses on the effects of Crocus sativus and its main ingredients, such as crocin, on cancer therapeutics. Methods We reviewed research data from saffron, a spice derived from the flower of Crocus sativus, and its constituents using the major databases, viz., Web of Science, SciFinder, and PubMed. Results and conclusion Saffron possesses free radical-scavenging properties and antitumor activities. Significant cancer chemopreventive effects have been shown in both in vitro and in vivo models. Based on current data, saffron and its ingredients could be considered as a promising candidate for clinical anticancer trials. PMID:23570520

  20. Role of saffron and its constituents on cancer chemoprevention.

    Science.gov (United States)

    Zhang, Zhiyu; Wang, Chong-Zhi; Wen, Xiao-Dong; Shoyama, Yukihiro; Yuan, Chun-Su

    2013-07-01

    Cancer dramatically impacts human life expectancy and quality of life. Natural substances from vegetables, herbs and spices could be beneficial in the prevention or treatment of a variety of cancers. Crocus sativus (Iridaceae), which has been used as a folk medicine for treating diseases for ages, showed obvious cancer chemoprevention potential. This article focuses on the effects of Crocus sativus and its main ingredients, such as crocin, on cancer therapeutics. We reviewed research data from saffron, a spice derived from the flower of Crocus sativus, and its constituents using the major databases, namely, Web of Science, SciFinder and PubMed. Saffron possesses free radical-scavenging properties and antitumor activities. Significant cancer chemopreventive effects have been shown in both in vitro and in vivo models. Based on current data, saffron and its ingredients could be considered as a promising candidate for clinical anticancer trials.

  1. Cancer Chemoprevention by Phytochemicals: Nature's Healing Touch.

    Science.gov (United States)

    Zubair, Haseeb; Azim, Shafquat; Ahmad, Aamir; Khan, Mohammad Aslam; Patel, Girijesh Kumar; Singh, Seema; Singh, Ajay Pratap

    2017-03-03

    Phytochemicals are an important part of traditional medicine and have been investigated in detail for possible inclusion in modern medicine as well. These compounds often serve as the backbone for the synthesis of novel therapeutic agents. For many years, phytochemicals have demonstrated encouraging activity against various human cancer models in pre-clinical assays. Here, we discuss select phytochemicals-curcumin, epigallocatechin-3-gallate (EGCG), resveratrol, plumbagin and honokiol-in the context of their reported effects on the processes of inflammation and oxidative stress, which play a key role in tumorigenesis. We also discuss the emerging evidence on modulation of tumor microenvironment by these phytochemicals which can possibly define their cancer-specific action. Finally, we provide recent updates on how low bioavailability, a major concern with phytochemicals, is being circumvented and the general efficacy being improved, by synthesis of novel chemical analogs and nanoformulations.

  2. Chemoprevention of Colorectal Cancer by Artocarpin, a Dietary Phytochemical from Artocarpus heterophyllus.

    Science.gov (United States)

    Sun, Guochuan; Zheng, Zongping; Lee, Mee-Hyun; Xu, Yijuan; Kang, Soouk; Dong, Zigang; Wang, Mingfu; Gu, Zhennan; Li, Haitao; Chen, Wei

    2017-05-03

    Artocarpus heterophyllus is an evergreen tree distributed in tropical regions, and its fruit (jackfruit) is well-known as the world's largest tree-borne fruit. Although A. heterophyllus has been widely used in folk medicines against inflammation, its potential in cancer chemoprevention remains unclear. Herein we identified artocarpin from A. heterophyllus as a promising colorectal cancer chemopreventive agent by targeting Akt kinase. Phenotypically, artocarpin exhibited selective cytotoxicity against human colon cancer cells. Artocarpin impaired the anchorage-independent growth capability, suppressed colon cancer cell growth, and induced a G1 phase cell cycle arrest which was followed by apoptotic as well as autophagic cell death. Mechanistic studies revealed that artocarpin directly targeted Akt 1 and 2 kinase activity evidenced by in vitro kinase assay, ex vivo binding assay as well as Akt downstream cellular signal transduction. Importantly, oral administration of artocarpin attenuated colitis-associated colorectal tumorigenesis in mice. Taken together, artocarpin, a bioactive component of A. heterophyllus, might merit investigation as a potential colorectal cancer chemopreventive agent.

  3. Jacalin Has Chemopreventive Effects on Colon Cancer Development

    Directory of Open Access Journals (Sweden)

    Thais Herrero Geraldino

    2017-01-01

    Full Text Available Colorectal cancer, which is one of the most common causes of cancer-related deaths worldwide, has a slow natural history that provides a great opportunity for prevention strategies. Plant-derived natural products have received considerable attention because of their inherent colorectal cancer chemopreventive effects. The plant lectin jacalin specifically recognizes the tumor-associated Thomsen-Friedenreich antigen and has antiproliferative effects on human colon cancer cells, highlighting its potential antitumor activity. To evaluate jacalin’s potential application in colorectal cancer chemoprevention, we studied its effects on the early stages of carcinogenesis. Balb/c mice were given 4 intrarectal deposits of 0.1 ml solution of Methyl-N′-Nitro-N-Nitroso-Guanidine (5 mg/ml twice a week (with a 3-day interval for 2 weeks. Starting 2 weeks before carcinogen administration, animals were treated orally with jacalin (0.5 and 25 μg three times a week (on alternate weekdays for 10 weeks. We show that jacalin treatment reduced the number of preneoplastic lesions in carcinogen-exposed mice. This anticarcinogenic activity was associated with decreased colonic epithelial cell proliferation and stromal COX-2 expression and with increased intestinal production of TNF-α. Our results demonstrate that jacalin is able to modulate the early stages of colon carcinogenesis and emphasize its promising chemopreventive activity in colorectal cancer.

  4. Jacalin Has Chemopreventive Effects on Colon Cancer Development.

    Science.gov (United States)

    Geraldino, Thais Herrero; Modiano, Patricia; Veronez, Luciana Chain; Flória-Santos, Milena; Garcia, Sergio Britto; Pereira-da-Silva, Gabriela

    2017-01-01

    Colorectal cancer, which is one of the most common causes of cancer-related deaths worldwide, has a slow natural history that provides a great opportunity for prevention strategies. Plant-derived natural products have received considerable attention because of their inherent colorectal cancer chemopreventive effects. The plant lectin jacalin specifically recognizes the tumor-associated Thomsen-Friedenreich antigen and has antiproliferative effects on human colon cancer cells, highlighting its potential antitumor activity. To evaluate jacalin's potential application in colorectal cancer chemoprevention, we studied its effects on the early stages of carcinogenesis. Balb/c mice were given 4 intrarectal deposits of 0.1 ml solution of Methyl-N'-Nitro-N-Nitroso-Guanidine (5 mg/ml) twice a week (with a 3-day interval) for 2 weeks. Starting 2 weeks before carcinogen administration, animals were treated orally with jacalin (0.5 and 25 μg) three times a week (on alternate weekdays) for 10 weeks. We show that jacalin treatment reduced the number of preneoplastic lesions in carcinogen-exposed mice. This anticarcinogenic activity was associated with decreased colonic epithelial cell proliferation and stromal COX-2 expression and with increased intestinal production of TNF-α. Our results demonstrate that jacalin is able to modulate the early stages of colon carcinogenesis and emphasize its promising chemopreventive activity in colorectal cancer.

  5. Polyphenols: Key Issues Involved in Chemoprevention of Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Sebastiano Cimino

    2012-01-01

    Full Text Available Prostate cancer is is the most common solid neoplasm and it is now recognized as one of the most important medical problems facing the male population. Due to its long latency and its identifiable preneoplastic lesions, prostate cancer is an ideal target tumor for chemoprevention. Different compounds are available and certainly polyphenols represent those with efficacy against prostate cancer. This review take a look at activity and properties of major polyphenolic substances, such as epigallocatechin-3-gallate, curcumin, resveratrol and the flavonoids quercetin and genistein. Although the current studies are limited, mechanisms of action of polyphenols added with the lack of side effects show a a start for future strategies in prostate chemoprevention.

  6. Cancer chemopreventive activity of compounds isolated from Waltheria indica.

    Science.gov (United States)

    Monteillier, Aymeric; Cretton, Sylvian; Ciclet, Olivier; Marcourt, Laurence; Ebrahimi, Samad Nejad; Christen, Philippe; Cuendet, Muriel

    2017-05-05

    Waltheria indica L. is traditionally used in several countries against inflammatory related diseases and cancer, mainly as a decoction of the aerial parts. The transcription factor NF-κB is known to induce tumor promotion and progression and is considered a major player in inflammation-driven cancers. Therefore, inhibitors of this pathway possess cancer chemopreventive and chemotherapeutic activities. This study aimed first to confirm the use of Waltheria indica as a traditional anti-inflammatory remedy by assessing the NF-κB inhibitory activity and then to identify the major bioactive compounds. The isolated compounds were also tested for their QR inducing property, a complementary strategy in cancer chemoprevention able to target tumor initiation. Finally, the relevance of in vitro results was examined by investigating the occurrence of the active compounds in traditional preparations. Compounds were isolated from the dichloromethane extract of the aerial parts using flash chromatography and semi-preparative HPLC. NF-κB inhibitory activity of pure compounds from Waltheria indica was assessed using a luciferase reporter assay in HEK293 cells. Their QR inducing activity was also assessed in Hepa1c1c7 cells. Twenty-nine compounds, of which 5 are new, were obtained from the dichloromethane extract and tested for their cancer chemoprevention activity. Eleven compounds inhibited NF-κB and/or induced QR in the low to mid µM range. Chrysosplenol E (20) was active in both tests. Two of the most potent NF-κB inhibitors, waltherione A (4) and waltherione C (5), as well as 20 were found in the traditional decoction, in which 4 and 5 were major compounds. The presence of potent NF-κB inhibitors and QR inducing compounds in the decoction of the aerial parts of Waltheria indica supports its traditional use in inflammatory-related diseases and cancer chemoprevention. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  7. Dietary phytochemicals and cancer chemoprevention: a review of the clinical evidence.

    Science.gov (United States)

    Kotecha, Ritesh; Takami, Akiyoshi; Espinoza, J Luis

    2016-08-09

    Cancer chemoprevention involves the use of different natural or biologic agents to inhibit or reverse tumor growth. Epidemiological and pre-clinical data suggest that various natural phytochemicals and dietary compounds possess chemopreventive properties, and in-vitro and animal studies support that these compounds may modulate signaling pathways involved in cell proliferation and apoptosis in transformed cells, enhance the host immune system and sensitize malignant cells to cytotoxic agents. Despite promising results from experimental studies, only a limited number of these compounds have been tested in clinical trials and have shown variable results. In this review, we summarize the data regarding select phytochemicals including curcumin, resveratrol, lycopene, folates and tea polyphenols with emphasis on the clinical evidence supporting the efficacy of these compounds in high-risk populations.

  8. Chemoprevention of Lung Cancer: Prospects and Disappointments in Human Clinical Trials

    Directory of Open Access Journals (Sweden)

    William N. Rom

    2013-01-01

    Full Text Available Decreasing the risk of lung cancer, or preventing its development in high-risk individuals, would have a huge impact on public health. The most effective means to decrease lung cancer incidence is to eliminate exposure to carcinogens. However, with recent advances in the understanding of pulmonary carcinogenesis and the identification of intermediate biomarkers, the prospects for the field of chemoprevention research have improved dramatically. Here we review the most recent research in lung cancer chemoprevention—focusing on those agents that have been investigated in human clinical trials. These agents fall into three major categories. First, oxidative stress plays an important role in pulmonary carcinogenesis; and therefore, antioxidants (including vitamins, selenium, green tea extracts, and isothiocyanates may be particularly effective in preventing the development of lung cancer. Second, inflammation is increasingly accepted as a crucial factor in carcinogenesis, and many investigators have focused on anti-inflammatory agents, such as glucocorticoids, NSAIDs, statins, and PPARγ agonists. Finally, the PI3K/AKT/mTOR pathway is recognized to play a central role in tobacco-induced carcinogenesis, and inhibitors of this pathway, including myoinositol and metformin, are promising agents for lung cancer prevention. Successful chemoprevention will likely require targeting of multiple pathways to carcinogenesis—both to minimize toxicity and maximize efficacy.

  9. Design, synthesis, and biological evaluation of callophycin A and analogues as potential chemopreventive and anticancer agents.

    Science.gov (United States)

    Shen, Li; Park, Eun-Jung; Kondratyuk, Tamara P; Guendisch, Daniela; Marler, Laura; Pezzuto, John M; Wright, Anthony D; Sun, Dianqing

    2011-11-01

    Callophycin A was originally isolated from the red algae Callophycus oppositifolius and shown to mediate anticancer and cytotoxic effects. In our collaborative effort to identify potential chemopreventive and anticancer agents with enhanced potency and selectivity, we employed a tetrahydro-β-carboline-based template inspired by callophycin A for production of a chemical library. Utilizing a parallel synthetic approach, 50 various functionalized tetrahydro-β-carboline derivatives were prepared and assessed for activities related to cancer chemoprevention and cancer treatment: induction of quinone reductase 1 (QR1) and inhibition of aromatase, nitric oxide (NO) production, tumor necrosis factor (TNF)-α-induced NFκB activity, and MCF7 breast cancer cell proliferation. Biological results showed that the n-pentyl urea S-isomer 6a was the strongest inducer of QR1 with an induction ratio (IR) value of 4.9 at 50 μM [the concentration to double the activity (CD)=3.8 μM] and its corresponding R-isomer 6f had an IR value of 4.3 (CD=0.2 μM). The isobutyl carbamate derivative 3d with R stereochemistry demonstrated the most potent inhibitory activity of NFκB, with the half maximal inhibitory concentration (IC(50)) value of 4.8 μM, and also showed over 60% inhibition at 50 μM of NO production (IC(50)=2.8 μM). The R-isomer urea derivative 6j, having an appended adamantyl group, exhibited the most potent MCF7 cell proliferation inhibitory activity (IC(50)=14.7 μM). The S-isomer 12a of callophycin A showed the most potent activity in aromatase inhibition (IC(50)=10.5 μM). Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Arsenic and skin cancer – Case report with chemoprevention

    OpenAIRE

    Uwe Wollina

    2016-01-01

    ABSTRACT Introduction: Arsenic is a potentially hazardous metalloid that can cause skin cancer. We want to demonstrate a case of chronic arsenicosis and the potential of chemoprevention with retinoids. Case Report: This is a case report of a 72-year-old male patient who was exposed to arsenics by dust and direct skin contact over 3 years in a chemical plant in the late fourties. He developed multiple arsenic keratosis clincialll resembling actinic keratoses, Bowen’s disease and palmar...

  11. Arsenic and skin cancer – Case report with chemoprevention

    Directory of Open Access Journals (Sweden)

    Uwe Wollina

    2016-04-01

    Full Text Available ABSTRACT Introduction: Arsenic is a potentially hazardous metalloid that can cause skin cancer. We want to demonstrate a case of chronic arsenicosis and the potential of chemoprevention with retinoids. Case Report: This is a case report of a 72-year-old male patient who was exposed to arsenics by dust and direct skin contact over 3 years in a chemical plant in the late fourties. He developed multiple arsenic keratosis clincialll resembling actinic keratoses, Bowen’s disease and palmar minute keratoses. To prevent a transformation into invasive cancer and to lower the burden of precancerous and in situ cancer lesions, he was treated orally with acitretin 20 mg/day. During 9 months of chemopreventive retinoid therapy a partial response of pre-existent skin lesions was noted. Treatment was well tolerated. During follow-up of 5 years no invasive malignancy developed. Conclusions: Intense exposure to arsenics during a relatively short period of 3 years bears a life-long health hazard with the delayed development of multiple in situ carcinomas and precancerous lesions. Chemoprevention with retinoids can induce a partial response.

  12. Curcumin and metformin-mediated chemoprevention of oral cancer is associated with inhibition of cancer stem cells.

    Science.gov (United States)

    Siddappa, Gangotri; Kulsum, Safeena; Ravindra, Doddathimmasandra Ramanjanappa; Kumar, Vinay V; Raju, Nalini; Raghavan, Nisheena; Sudheendra, Holalugunda Vittalamurthy; Sharma, Anupam; Sunny, Sumsum P; Jacob, Tina; Kuruvilla, Binu T; Benny, Merina; Antony, Benny; Seshadri, Mukund; Lakshminarayan, Padma; Hicks, Wesley; Suresh, Amritha; Kuriakose, Moni A

    2017-11-01

    Effective chemoprevention is critical for improving outcomes of oral cancer. As single agents, curcumin and metformin are reported to exhibit chemopreventive properties, in vitro as well as in patients with oral cancer. In this study, the chemopreventive efficacy of this drug combination was tested in a 4-nitro quinoline-1-oxide (4NQO) induced mice oral carcinogenesis model. Molecular analysis revealed a cancer stem cell (CSC)-driven oral carcinogenic progression in this model, wherein a progressive increase in the expression of CSC-specific markers (CD44 and CD133) was observed from 8th to 25th week, at transcript (40-100-fold) and protein levels (P ≤ 0.0001). Chemopreventive treatment of the animals at 17th week with curcumin and metformin indicated that the combination regimen decreased tumor volume when compared to the control arm (0.69+0.03 vs 6.66+2.4 mm 3 ; P = 0.04) and improved overall survival of the animals (P = 0.03). Assessment of the molecular status showed an overall downregulation of CSC markers in the treatment arms as compared to the untreated control. Further, in vitro assessment of the treatment on the primary cells generated from progressive stages of 4NQO-induced mice tissue showed a concordant and consistent downregulation of the CSC markers following combination treatment (P oral squamous cell carcinoma through a CSC-associated mechanism. © 2017 Wiley Periodicals, Inc.

  13. Chemopreventive potential of natural compounds in head and neck cancer.

    Science.gov (United States)

    Rahman, Mohammad Aminur; Amin, A R M Ruhul; Shin, Dong M

    2010-01-01

    Head and neck squamous cell carcinoma (HNSCC) is one of the most fatal cancers worldwide. Despite advances in the management of HNSCC, the overall survival for patients has not improved significantly due to advanced stages at diagnosis, high recurrence rate after surgical removal, and second primary tumor development, which underscore the importance of novel strategies for cancer prevention. Cancer chemoprevention, the use of natural or synthetic compounds to prevent, arrest, or reverse the process of carcinogenesis at its earliest stages, aims to reverse premalignancies and prevent second primary tumors. Genomics and proteomics information including initial mutation, cancer promotion, progression, and susceptibility has brought molecularly targeted therapies for drug development. The development of preventive approaches using specific natural or synthetic compounds, or both, requires a depth of understanding of the cross-talk between cancer signaling pathways and networks to retain or enhance chemopreventive activity while reducing known toxic effects. Many natural dietary compounds have been identified with multiple molecular targets, effective in the prevention and treatment of cancer. This review describes recent advances in the understanding of the complex signaling networks driving cancer progression and of molecularly targeted natural compounds under preclinical and clinical investigation.

  14. Burden and Chemoprevention of Skin Cancer

    NARCIS (Netherlands)

    L.M. Hollestein (Loes)

    2013-01-01

    markdownabstractThe incidence of skin cancer is increasing in the Netherlands since 1989, the first year of the Netherlands Cancer Registry (NCR). In 2010 more than 43,000 patients were newly diagnosed with skin cancer in the Netherlands. During a life time at least 1 in 5 persons living in

  15. Shrimp Lipids: A Source of Cancer Chemopreventive Compounds

    Directory of Open Access Journals (Sweden)

    Armando Burgos-Hernández

    2013-10-01

    Full Text Available Shrimp is one of the most popular seafoods worldwide, and its lipids have been studied for biological activity in both, muscle and exoskeleton. Free fatty acids, triglycerides, carotenoids, and other lipids integrate this fraction, and some of these compounds have been reported with cancer chemopreventive activities. Carotenoids and polyunsaturated fatty acids have been extensively studied for chemopreventive properties, in both in vivo and in vitro studies. Their mechanisms of action depend on the lipid chemical structure and include antioxidant, anti-proliferative, anti-mutagenic, and anti-inflammatory activities, among others. The purpose of this review is to lay groundwork for future research about the properties of the lipid fraction of shrimp.

  16. New Approaches to Chemoprevention of Breast Cancer

    National Research Council Canada - National Science Library

    Sporn, Michael

    1998-01-01

    Triterpenoids, natural products related to steroids and retinolds, represent an important class of new structures for drug discovery, with potential applications in many fields of medicine, particularly cancer...

  17. New Approaches to Chemoprevention of Breast Cancer

    National Research Council Canada - National Science Library

    Sporn, Michael

    1997-01-01

    Triterpenoids, natural products related to steroids and retinoids, represent an important class of new structures for drug discovery, with potential applications in many fields of medicine, particularly cancer...

  18. The potential of statins for individualized colorectal cancer chemoprevention.

    Science.gov (United States)

    Jacobs, Rutger J; Kodach, Liudmila L; Hardwick, James C H

    2011-12-01

    Colorectal cancer is a leading cause of death by cancer in the western world. Despite major progress, even new chemotherapeutic regimens have had relatively little impact on long term survival in the approximately 50% of patients with advanced disease at presentation meaning that prevention is the only realistic way to reduce the burden of this disease. Many countries have implemented population-based screening methods to prevent colorectal cancer by the physical removal of its precursor lesion the adenoma, or to detect cancer at an earlier stage when it is amenable to surgical cure. However these programs have only been shown to reduce colorectal cancer deaths by 30% in those screened and therefore new or complimentary approaches are needed. One such approach is chemoprevention. A number of compounds have shown potential in reducing the incidence of colorectal cancer. Most widely known are NSAIDs but recently inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, also known as statins, commonly prescribed medications that lower serum cholesterol, have been shown to reduce colorectal cancer incidence. A critical issue in chemoprevention is the weighing of benefits against risks. In chemoprevention this balance is likely to be unfavourable when used in a wide unselected population even for the safest of compounds. Therapy should therefore be tailored to the individual patient. The balance will be more favourable in high risk groups such as individuals especially susceptible to neoplasia because of environmental risk factors, patients with inflammatory bowel disease, those with a hereditary predisposition and patients with a previous history of colorectal cancer or polyps. Furthermore colorectal cancer is not one disease but a heterogeneous group of diseases with different underlying molecular mechanisms. It is likely that both prevention and therapy will need to be tailored to the molecular subtype of the cancer in question. This may explain

  19. Clinical cancer chemoprevention: From the hepatitis B virus (HBV) vaccine to the human papillomavirus (HPV) vaccine.

    Science.gov (United States)

    Tsai, Horng-Jyh

    2015-04-01

    Approximately 2 million new cancer cases are attributed to infectious agents each year worldwide. Vaccines for the hepatitis B virus (HBV), a risk factor of hepatocellular cancer, and human papillomavirus (HPV), a risk factor of cervical cancer, are considered major successes in clinical chemoprevention of cancer. In Taiwan, the first evidence of cancer prevention through vaccinations was provided by HBV vaccination data in infants. The Taiwanese HBV vaccination program has since become a model immunization schedule for newborns worldwide. Persistent infection with high-risk HPV is generally accepted as prerequisite for cervical cancer diagnosis; however, cervical cancer is a rare complication of HPV infections. This is due to the fact that such infections tend to be transient. The safety and efficacy of both available HPV quadrivalent vaccine and bivalent vaccine are not in doubt at the present time. Until a human cytomegalovirus (CMV) vaccine becomes available, simple hygienic practices, such as hand washing, can prevent CMV infection both before and during pregnancy. Each country should establish her official guidelines regarding which vaccines should be used to treat various conditions, the target population (i.e., universal or limited to a selected population), and the immunization schedules. After a vaccine is recommended, decisions regarding reimbursement by the public health care fund are evaluated. The guidelines become part of the immunization schedule, which is updated annually and published in the official bulletin. In conclusion, both HBV and HPV vaccines are considered major successes in the chemoprevention of cancer. Copyright © 2015. Published by Elsevier B.V.

  20. Chemoprevention of Breast Cancer: The Paradox of Evidence versus Advocacy Inaction

    Directory of Open Access Journals (Sweden)

    Rakhshanda Layeequr Rahman

    2012-10-01

    Full Text Available Women who are at high risk of breast cancer can be offered chemoprevention. Chemoprevention strategies have expanded over the past decade and include selective receptor modulator inhibitors and aromatase inhibitors. Physicians are expected to provide individualized risk assessments to identify high risk women who may be eligible for chemoprevention. It is prudent that physicians utilize a shared decision approach when counseling high risk women about their preventive options. Barriers and misperceptions however exist with patient and physician acceptance of chemoprevention and continue to impede uptake of chemoprevention as a strategy to reduce breast cancer risk. Programs to increase awareness and elucidate the barriers are critical for women to engage in cancer prevention and promote chemoprevention adherence.

  1. Biological Basis for Chemoprevention of Ovarian Cancer

    National Research Council Canada - National Science Library

    Berchuck, Andrew

    2006-01-01

    To achieve a better understanding of the etiology of ovarian cancer we have initiated a case-control study that considers genetic susceptibility epidemiologic risk factors and acquired genetic alterations...

  2. Chemopreventive agents attenuate rapid inhibition of gap junctional intercellular communication induced by environmental toxicants

    Czech Academy of Sciences Publication Activity Database

    Babica, Pavel; Čtveráčková, Lucie; Lenčešová, Zuzana; Trosko, J. E.; Upham, B. L.

    2016-01-01

    Roč. 68, č. 5 (2016), s. 827-837 ISSN 0163-5581 R&D Projects: GA MŠk LH12034 Institutional support: RVO:67985939 Keywords : gap junctional intercellular communication * chemopreventive agents * environmental toxicants Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 2.447, year: 2016

  3. Chemoprevention of Breast Cancer by Dietary Polyphenols.

    Science.gov (United States)

    Mocanu, Maria-Magdalena; Nagy, Péter; Szöllősi, János

    2015-12-17

    The review will discuss in detail the effects of polyphenols on breast cancer, including both the advantages and disadvantages of the applications of these natural compounds. First, we focus on the characterization of the main classes of polyphenols and then on in vitro and in vivo experiments carried out in breast cancer models. Since the therapeutic effects of the administration of a single type of polyphenol might be limited because of the reduced bioavailability of these drugs, investigations on combination of several polyphenols or polyphenols with conventional therapy will also be discussed. In addition, we present recent data focusing on clinical trials with polyphenols and new approaches with nanoparticles in breast cancer. Besides the clinical and translational findings this review systematically summarizes our current knowledge about the molecular mechanisms of anti-cancer effects of polyphenols, which are related to apoptosis, cell cycle regulation, plasma membrane receptors, signaling pathways and epigenetic mechanisms. At the same time the effects of polyphenols on primary tumor, metastasis and angiogenesis in breast cancer are discussed. The increasing enthusiasm regarding the combination of polyphenols and conventional therapy in breast cancer might lead to additional efforts to motivate further research in this field.

  4. Nicotinamide and skin cancer chemoprevention: The jury is still out.

    Science.gov (United States)

    Gilmore, Stephen J

    2018-02-01

    Following the publication of the results of a Phase III trial, the administration of oral nicotinamide has been widely advocated as effective in non-melanoma skin cancer chemoprevention in high-risk individuals. However, I performed a Bayesian analysis of the reported findings and show there is insufficient evidence to demonstrate its efficacy, highlighting the significant probability that the positive conclusions drawn will not be reproducible. Given the potential widespread use of oral nicotinamide, future position statements regarding its efficacy are likely to require higher standards of evidence. © 2017 The Australasian College of Dermatologists.

  5. Combination chemoprevention with diclofenac, calcipotriol and difluoromethylornithine inhibits development of non-melanoma skin cancer in mice.

    Science.gov (United States)

    Pommergaard, Hans-Christian; Burcharth, Jakob; Rosenberg, Jacob; Raskov, Hans

    2013-08-01

    With increasing incidence of non-melanoma skin cancer (NMSC), focus on chemoprevention of this disease is growing. The aim of this study was to evaluate topical combination therapies as chemoprevention of UV radiation-induced tumors in a mouse model. A total of 160 SKH-1 mice were randomized to one placebo group and four chemoprevention groups (diclofenac plus difluoromethylornithine; diclofenac plus calcipotriol; difluoromethylornithine plus calcitriol; and diclofenac plus difluoromethylornithine plus calcipotriol). The mice received UVB radiation for 20 weeks followed by 17 weeks with topical application of chemoprevention. The number of mice with tumors, number of tumors per group and tumor area size were compared using a linear regression model. Chemoprevention with diclonefac plus calcipotriol and diclonefac plus difluoromethylornithine had a significant inhibiting effect on the number of tumors per group and the area of tumors. Moreover, diclonefac plus difluoromethylornithine had a significant inhibiting effect on the number of mice with tumors. Potentially, non-melanoma skin cancer in humans may be prevented with these agents with few adverse effects. Therefore, clinical studies are needed to determine their therapeutic/preventive effect and possible adverse effects.

  6. Biological Basis for Chemoprevention of Ovarian Cancer

    Science.gov (United States)

    2006-10-01

    During the study interview a thorough history of the menstrual cycle and reproductive experiences of the study participants is obtained from each...cancer.24 The scope of vitamin D deficiency extends well beyond the elderly however, as widespread vitamin D deficiency is common in adolescents and...gene in ras-transformed keratinocytes demonstrates that locally produced 1alpha,25-dihydroxyvitamin D3 suppresses growth and induces differentiation in

  7. New Enlightenment of Skin Cancer Chemoprevention through Phytochemicals: In Vitro and In Vivo Studies and the Underlying Mechanisms.

    Science.gov (United States)

    Singh, Madhulika; Suman, Shankar; Shukla, Yogeshwer

    2014-01-01

    Skin cancer is still a major cause of morbidity and mortality worldwide. Skin overexposure to ultraviolet irradiations, chemicals, and several viruses has a capability to cause severe skin-related disorders including immunosuppression and skin cancer. These factors act in sequence at various steps of skin carcinogenesis via initiation, promotion, and/or progression. These days cancer chemoprevention is recognized as the most hopeful and novel approach to prevent, inhibit, or reverse the processes of carcinogenesis by intervention with natural products. Phytochemicals have antioxidant, antimutagenic, anticarcinogenic, and carcinogen detoxification capabilities thereby considered as efficient chemopreventive agents. Considerable efforts have been done to identify the phytochemicals which may possibly act on one or several molecular targets that modulate cellular processes such as inflammation, immunity, cell cycle progression, and apoptosis. Till date several phytochemicals in the light of chemoprevention have been studied by using suitable skin carcinogenic in vitro and in vivo models and proven as beneficial for prevention of skin cancer. This revision presents a comprehensive knowledge and the main molecular mechanisms of actions of various phytochemicals in the chemoprevention of skin cancer.

  8. New Enlightenment of Skin Cancer Chemoprevention through Phytochemicals: In Vitro and In Vivo Studies and the Underlying Mechanisms

    Science.gov (United States)

    Singh, Madhulika; Suman, Shankar; Shukla, Yogeshwer

    2014-01-01

    Skin cancer is still a major cause of morbidity and mortality worldwide. Skin overexposure to ultraviolet irradiations, chemicals, and several viruses has a capability to cause severe skin-related disorders including immunosuppression and skin cancer. These factors act in sequence at various steps of skin carcinogenesis via initiation, promotion, and/or progression. These days cancer chemoprevention is recognized as the most hopeful and novel approach to prevent, inhibit, or reverse the processes of carcinogenesis by intervention with natural products. Phytochemicals have antioxidant, antimutagenic, anticarcinogenic, and carcinogen detoxification capabilities thereby considered as efficient chemopreventive agents. Considerable efforts have been done to identify the phytochemicals which may possibly act on one or several molecular targets that modulate cellular processes such as inflammation, immunity, cell cycle progression, and apoptosis. Till date several phytochemicals in the light of chemoprevention have been studied by using suitable skin carcinogenic in vitro and in vivo models and proven as beneficial for prevention of skin cancer. This revision presents a comprehensive knowledge and the main molecular mechanisms of actions of various phytochemicals in the chemoprevention of skin cancer. PMID:24757666

  9. New Enlightenment of Skin Cancer Chemoprevention through Phytochemicals: In Vitro and In Vivo Studies and the Underlying Mechanisms

    Directory of Open Access Journals (Sweden)

    Madhulika Singh

    2014-01-01

    Full Text Available Skin cancer is still a major cause of morbidity and mortality worldwide. Skin overexposure to ultraviolet irradiations, chemicals, and several viruses has a capability to cause severe skin-related disorders including immunosuppression and skin cancer. These factors act in sequence at various steps of skin carcinogenesis via initiation, promotion, and/or progression. These days cancer chemoprevention is recognized as the most hopeful and novel approach to prevent, inhibit, or reverse the processes of carcinogenesis by intervention with natural products. Phytochemicals have antioxidant, antimutagenic, anticarcinogenic, and carcinogen detoxification capabilities thereby considered as efficient chemopreventive agents. Considerable efforts have been done to identify the phytochemicals which may possibly act on one or several molecular targets that modulate cellular processes such as inflammation, immunity, cell cycle progression, and apoptosis. Till date several phytochemicals in the light of chemoprevention have been studied by using suitable skin carcinogenic in vitro and in vivo models and proven as beneficial for prevention of skin cancer. This revision presents a comprehensive knowledge and the main molecular mechanisms of actions of various phytochemicals in the chemoprevention of skin cancer.

  10. Australian clinicians and chemoprevention for women at high familial risk for breast cancer

    Directory of Open Access Journals (Sweden)

    Keogh Louise A

    2009-05-01

    Full Text Available Abstract Objectives Effective chemoprevention strategies exist for women at high risk for breast cancer, yet uptake is low. Physician recommendation is an important determinant of uptake, but little is known about clinicians' attitudes to chemoprevention. Methods Focus groups were conducted with clinicians at five Family Cancer Centers in three Australian states. Discussions were recorded, transcribed and analyzed thematically. Results Twenty three clinicians, including genetic counselors, clinical geneticists, medical oncologists, breast surgeons and gynaecologic oncologists, participated in six focus groups in 2007. The identified barriers to the discussion of the use of tamoxifen and raloxifene for chemoprevention pertained to issues of evidence (evidence for efficacy not strong enough, side-effects outweigh benefits, oophorectomy superior for mutation carriers, practice (drugs not approved for chemoprevention by regulatory authorities and not government subsidized, chemoprevention not endorsed in national guidelines and not many women ask about it, and perception (clinicians not knowledgeable about chemoprevention and women thought to be opposed to hormonal treatments. Conclusion The study demonstrated limited enthusiasm for discussing breast cancer chemoprevention as a management option for women at high familial risk. Several options for increasing the likelihood of clinicians discussing chemoprevention were identified; maintaining up to date national guidelines on management of these women and education of clinicians about the drugs themselves, the legality of "off-label" prescribing, and the actual costs of chemopreventive medications.

  11. Drug delivery strategies for chemoprevention of UVB-induced skin cancer: A review.

    Science.gov (United States)

    Bagde, Arvind; Mondal, Arindam; Singh, Mandip

    2018-01-01

    Annually, more skin cancer cases are diagnosed than the collective incidence of the colon, lung, breast, and prostate cancer. Persistent contact with sunlight is a primary cause for all the skin malignancies. UVB radiation induces reactive oxygen species (ROS) production in the skin which eventually leads to DNA damage and mutation. Various delivery approaches for the skin cancer treatment/prevention have been evolving and are directed toward improvements in terms of delivery modes, therapeutic agents, and site-specificity of therapeutics delivery. The effective chemoprevention activity achieved is based on the efficiency of the delivery system used and the amount of the therapeutic molecule deposited in the skin. In this article, we have discussed different studies performed specifically for the chemoprevention of UVB-induced skin cancer. Ultra-flexible nanocarriers, transethosomes nanocarriers, silica nanoparticles, silver nanoparticles, nanocapsule suspensions, microemulsion, nanoemulsion, and polymeric nanoparticles which have been used so far to deliver the desired drug molecule for preventing the UVB-induced skin cancer. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Oxidative stress and dietary phytochemicals: Role in cancer chemoprevention and treatment.

    Science.gov (United States)

    Chikara, Shireen; Nagaprashantha, Lokesh Dalasanur; Singhal, Jyotsana; Horne, David; Awasthi, Sanjay; Singhal, Sharad S

    2018-01-28

    Several epidemiological observations have shown an inverse relation between consumption of plant-based foods, rich in phytochemicals, and incidence of cancer. Phytochemicals, secondary plant metabolites, via their antioxidant property play a key role in cancer chemoprevention by suppressing oxidative stress-induced DNA damage. In addition, they modulate several oxidative stress-mediated signaling pathways through their anti-oxidant effects, and ultimately protect cells from undergoing molecular changes that trigger carcinogenesis. In several instances, however, the pro-oxidant property of these phytochemicals has been observed with respect to cancer treatment. Further, in vitro and in vivo studies show that several phytochemicals potentiate the efficacy of chemotherapeutic agents by exacerbating oxidative stress in cancer cells. Therefore, we reviewed multiple studies investigating the role of dietary phytochemicals such as, curcumin (turmeric), epigallocatechin gallate (EGCG; green tea), resveratrol (grapes), phenethyl isothiocyanate (PEITC), sulforaphane (cruciferous vegetables), hesperidin, quercetin and 2'-hydroxyflavanone (2HF; citrus fruits) in regulating oxidative stress and associated signaling pathways in the context of cancer chemoprevention and treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Biochemical and molecular mechanisms underlying the chemopreventive efficacy of rosmarinic acid in a rat colon cancer.

    Science.gov (United States)

    Venkatachalam, Karthikkumar; Gunasekaran, Sivagami; Namasivayam, Nalini

    2016-11-15

    To shed light on colon cancer chemoprevention, natural phytochemicals attract researchers by virtue of their beneficial biological effects. The chemopreventive potential of rosmarinic acid (RA) was tested by using the colon carcinogen, 1,2-dimethylhydrazine (DMH) by evaluating the Aberrant crypt foci (ACF), tumour incidence, lipid peroxidative byproducts, phase I & II drug metabolizing enzymes, cell proliferative and apoptotic proteins. Rats were divided into six groups and received modified pellet diet. Group 1 served as control rats, group 2 rats received RA (5mg/kg b.w. p.o.), rats in groups 3-6 received DMH (20mg/kg b.w., s.c.) for the first fifteen weeks. In addition to DMH, groups 4-6 received RA at the dose of 5mg/kg b.w. during initiation, post initiation stages and also for the entire study period. DMH treated rats showed an increase in the development of ACF, tumour formation and multiplicity and decrease in lipid peroxidative byproducts. Moreover, it modulates xenobiotic enzymes and reduces the expressions of proapoptotic proteins; increases expressions of anti apoptotic proteins at the end of the study. Supplementation with RA to carcinogen treated rats protected them from the above deleterious effects caused by DMH and thus RA may be used as a potent chemopreventive agent. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. "Nutritional and chemopreventive anti-cancer agents up-regulate expression of p27Kip1, a cyclin-dependent kinase inhibitor, in mouse JB6 epidermal and human MCF7, MDA-MB-321 and AU565 breast cancer cells"

    Directory of Open Access Journals (Sweden)

    Eto Isao

    2006-08-01

    Full Text Available Abstract Background p27(Kip1 is a cyclin-dependent kinase inhibitor. When up-regulated, p27 inhibits G1-to-S phase transition of the cell cycle. This report addresses the question of whether various nutritional and chemopreventive anti-cancer agents up-regulate the expression of p27 in preneoplastic and neoplastic cells. Results Experimental evidence presented in the first half of this report shows that these agents fairly faithfully up-regulate expression of p27 in mouse epidermal (JB6 and human breast cancer (MCF7, MDA-MB-321, and AU565 cells. Up-regulation appears to be specific to p27 because expression of cyclin D1, E, and A, and p21Cip1/Waf1 was not modulated by these agents. Up-regulation of the expression of p27 is likely due to the activation of translation rather than transcription of p27 because (a up-regulation is mediated by the 5'-untranslated region (-575 of the p27 gene and (b the antibiotic actinomycin D, an inhibitor of transcription, did not attenuate the up-regulation of p27. This latter finding is likely to preclude the existence of cryptic transcription factor binding site(s in the 5'-untranslated region of p27 gene. The experimental evidence, presented in the second half of this report, was obtained using the 5'-untranslated region (-575 of p27 gene. The evidence suggests that cancer preventive agents up-regulate expression of p27 by at least four different molecular signaling pathways: (a Caloric restriction is likely to up-regulate p27 expression via 5'-AMP-activated protein kinase (AMPK; a metabolic energy sensor or cellular fuel gauge, tuberous sclerosis complex (TSC, and mammalian target of rapamycin (mTOR. Amino acid deficiencies also up-regulate the expression of p27 using some components of this pathway. (b 4-Hydroxytamoxifen (but not tamoxifen, genistein (but not genistin, daidzein, and probably other nutritional and chemopreventive anti-cancer agents could up-regulate expression of p27 via receptor protein

  15. Chemoprevention of Breast Cancer by Mimicking the Protective Effect of Early First Birth. Addendum

    Science.gov (United States)

    2013-03-01

    densities and breast cancer risk. Cancer Epidemiol Biomarkers Prev 1998;7:1133-44. 4. Bartow SA, Pathak DR, Mettler FA. Radiographic microcalcification ...AD_________________ Award Number: W81XWH-05-1-0390 TITLE: Chemoprevention of breast cancer by...REPORT TYPE Final addendum 3. DATES COVERED 2 May 2012 – 2 February 2013 4. TITLE AND SUBTITLE Chemoprevention of breast cancer by mimicking the

  16. Chemoprevention by grape seed extract and genistein in carcinogen-induced mammary cancer in rats is diet dependent.

    Science.gov (United States)

    Kim, Helen; Hall, Patti; Smith, Michelle; Kirk, Marion; Prasain, Jeevan K; Barnes, Stephen; Grubbs, Clinton

    2004-12-01

    Many popular dietary supplements are enriched in polyphenols such as the soy isoflavones, tea catechins, and resveratrol (from grape skins), each of which has been shown to have chemopreventive activity in cellular models of cancer. The proanthocyanidins, which are oligomers of the catechins, are enriched in grape seeds and form the basis of the dietary supplement grape seed extract (GSE). Evidence suggests that the proanthocyanidins may be metabolized to the monomeric catechins. This study was carried out to determine whether GSE added to rodent diets protected against carcinogen-induced mammary tumorigenesis in rats and whether this was affected by the composition of the whole diet. Female rats were begun on 5%, 1.25%, or 0% (control) GSE-supplemented diets at age 35 d. At age 50 d they were administered 7,12-dimethylbenz[a]anthracene (DMBA) in sesame oil at 80 mg/kg body weight. They were weighed and monitored weekly for tumor development until 120 d after DMBA administration. Administration of GSE in AIN-76A diet did not show any protective activity of GSE against DMBA-induced breast cancer. However, administration of GSE in a laboratory dry food diet (Teklad 4% rodent diet) resulted in a 50% reduction in tumor multiplicity. In similar experiments, genistein administered in AIN-76A diet also failed to show chemopreventive activity against the carcinogen N-methyl-N-nitrosourea; however, when administered at the same dose in the Teklad 4% rodent diet, genistein exhibited significant chemopreventive activity (44-61%). These results demonstrate that GSE is chemopreventive in an animal model of breast cancer; moreover, the diet dependency of the chemopreventive activity for both GSE and genistein suggests that whether or not a compound is chemopreventive may depend on the diet in which the agent is administered.

  17. Chemoprevention of Melanoma

    Science.gov (United States)

    Madhunapantula, SubbaRao V.; Robertson, Gavin P.

    2013-01-01

    Despite advances in drug discovery programs and molecular approaches for identifying the drug targets, incidence and mortality rates due to melanoma continues to rise at an alarming rate. Existing preventive strategies generally involve mole screening followed by surgical removal of the benign nevi and abnormal moles. However, due to lack of effective programs for screening and disease recurrence after surgical resection there is a need for better chemopreventive agents. Although sunscreens have been used extensively for protecting from UV-induced skin cancer, results of correlative population based studies are controversial, requiring further authentication to conclusively confirm the chemoprotective efficacy of sunscreens. Certain studies suggest increased skin-cancer rates in sunscreen users. Therefore, effective chemopreventive agents for preventing melanoma are urgently required. This book-chapter, reviews the current understanding regarding melanoma chemoprevention and the various strategies used to accomplish this objective. PMID:22959032

  18. Use of letrozole as a chemopreventive agent in aromatase overexpressing transgenic mice.

    Science.gov (United States)

    Luthra, Roopa; Kirma, Nameer; Jones, Jeremy; Tekmal, Rajeshwar Rao

    2003-09-01

    Our recent studies have shown that overexpression of aromatase results in increased tissue estrogenic activity and induction of hyperplastic and dysplastic lesions in mammary glands, and gynecomastia and testicular cancer in male aromatase transgenic mice. Our studies also have shown that aromatase overexpression-induced changes in mammary glands can be abrogated with very low concentrations of letrozole, an aromatase inhibitor without any effect on normal physiology. In the present study, we have examined the effect of prior low dose letrozole treatment on pregnancy and lactation. We have also investigated the effect of low dose letrozole treatment on subsequent mammary growth and biochemical changes in these animals. There was no change in the litter size, birth weight and no visible birth defects in letrozole-treated animals. Although, there was an insignificant increase in mammary growth in aged animals after 6 weeks of letrozole treatment, the levels of expression of estrogen receptor, progesterone receptor and genes involved in cell cycle and cell proliferation remained low compared to control untreated animals. These observations indicate that aromatase inhibitors such as letrozole can be used as chemopreventive agents without effecting normal physiology in aromatase transgenic mice.

  19. Telomerase as an Androgen Receptor-Regulated Target in Selenium Chemoprevention of Prostate Cancer

    Science.gov (United States)

    2011-04-01

    and Vita- min E Chemoprevention Trial (SELECT) indicated that supplementation of healthy individuals with nutritional dose of selenium did not reduce...were conducted by using pharmacologic doses of selenium , not the nutritional dose that was used in the SELECT. Therefore, the negative SELECT finding...Regulated Target in Selenium Chemoprevention of Prostate Cancer PRINCIPAL INVESTIGATOR: Shuang Liu, Ph.D

  20. Systemic retinoids for chemoprevention of non-melanoma skin cancer in high-risk patients.

    Science.gov (United States)

    Marquez, Christina; Bair, Sarah M; Smithberger, Erica; Cherpelis, Basil S; Glass, L Frank

    2010-07-01

    Patients at high risk for the development of multiple non-melanoma skin cancers, especially those receiving immunosuppressive medications following solid organ transplantation, are candidates for chemoprophylaxis. In patients where photo-protection and topical medications are insufficient to prevent the growth of new cancers, there is considerable evidence that oral retinoids, including vitamin A, and synthetics such as isotretinoin, etretinate and acitretin are efficacious in this regard. This manuscript is a review of the literature regarding the use of these agents for chemoprophylaxis of non-melanoma skin cancer. Also included is anecdotal evidence that bexarotene, a rexinoid, may be as effective as acitretin in terms of chemoprevention, with a comparable side effects at doses recommended for chemoprophylaxis.

  1. Cancer chemopreventive effects of the flavonoid-rich fraction isolated from papaya seeds.

    Science.gov (United States)

    Pathak, Neelam; Khan, Saba; Bhargava, Arpit; Raghuram, Gorantla V; Jain, Deepika; Panwar, Hariom; Samarth, Ravindra M; Jain, Subodh K; Maudar, Kewal K; Mishra, Dinesh K; Mishra, Pradyumna K

    2014-01-01

    Intervention to decelerate, arrest, or reverse the process of carcinogenesis by the use of either natural or synthetic agents individually or in combination has emerged as a promising and pragmatic medical approach to reduce cancer risk. In the present study, we examined the cancer chemopreventive potential of a flavonoid-rich fraction isolated from the seeds of Carica papaya, a plant traditionally referred to as papaw. The flavonoid-enriched benzene fraction of the aqueous extract exerted its anticancer properties in vitro through cytoprotection, antioxidative and antiinflammatory mechanisms and genoprotection in response to isocyanate-induced carcinogenicity. Medium-term anticarcinogenicity and 2-stage skin papillomagenesis studies conducted in benzopyrene-induced lung carcinogenesis and 7,12-dimethyl benz(a)anthracene-mediated skin papillomagenesis mouse models further validated our in vitro observations. This is the first demonstration of chemopreventive activities of papaya seed products, however, further studies to understand the subtle targets of intracellular signaling pathways, pharmacological profile and toxicological safety of this bioactive fraction are essential to pave the way for successful clinical translation. Our study supports the inverse association between dietary flavonoid intake and cancer risk.

  2. Crocus sativus L. (saffron) for cancer chemoprevention: A mini review.

    Science.gov (United States)

    Bhandari, Prasan R

    2015-04-01

    Cancer is one of the most feared diseases globally and there has been a sustained rise in its incidence in both developing and developed countries. Despite the growing therapeutic options for patients with cancer, their efficacy is time-limited and non-curative. Hence to overcome these drawbacks, an incessant screening for superior and safer drugs has been ongoing for numerous decades, resulting in the detection of anti-cancer properties of several phytochemicals. Chemoprevention using readily available natural substances from vegetables, fruits, herbs and spices is one of the significantly important approaches for cancer prevention in the present era. Among the spices, Crocus sativus L. (saffron; fān hóng huā) has generated interest because pharmacological experiments have established numerous beneficial properties including radical scavenging, anti-mutagenic and immuno-modulating effects. The more powerful components of saffron are crocin, crocetin and safranal. Studies in animal models and with cultured human malignant cell lines have demonstrated antitumor and cancer preventive activities of saffron and its main ingredients. This review provides a brief insight into the anticancer properties of saffron and its components.

  3. Black tea: Phytochemicals, cancer chemoprevention, and clinical studies.

    Science.gov (United States)

    Singh, Brahma N; Rawat, A K S; Bhagat, R M; Singh, B R

    2017-05-03

    Tea (Camellia sinensis L.) is the most popular, flavored, functional, and therapeutic non-alcoholic drink consumed by two-thirds of the world's population. Black tea leaves are reported to contain thousands of bioactive constituents such as polyphenols, amino acids, volatile compounds, and alkaloids that exhibit a range of promising pharmacological properties. Due to strong antioxidant property, black tea inhibits the development of various cancers by regulating oxidative damage of biomolecules, endogenous antioxidants, and pathways of mutagen and transcription of antioxidant gene pool. Regular drinking of phytochemicals-rich black tea is linked to regulate several molecular targets, including COX-2, 5-LOX, AP-1, JNK, STAT, EGFR, AKT, Bcl2, NF-κB, Bcl-xL, caspases, p53, FOXO1, TNFα, PARP, and MAPK, which may be the basis of how dose of black tea prevents and cures cancer. In vitro and preclinical studies support the anti-cancer activity of black tea; however, its effect in human trails is uncertain, although more clinical experiments are needed at molecular levels to understand its anti-cancer property. This review discusses the current knowledge on phytochemistry, chemopreventive activity, and clinical applications of black tea to reveal its anti-cancer effect.

  4. Chemoprevention targets for tobacco-related head and neck cancer: past lessons and future directions.

    Science.gov (United States)

    Sheth, Siddharth H; Johnson, Daniel E; Kensler, Thomas W; Bauman, Julie E

    2015-06-01

    Progress toward identifying an effective chemopreventive agent to reduce the incidence of head and neck squamous cell carcinoma (HNSCC) has been limited by poor efficacy and intolerable toxicity profiles. In this review, we summarize the biological basis of HNSCC chemoprevention, and outline challenges associated with identifying appropriate high-risk HNSCC populations for chemoprevention studies. We discuss findings and lessons learned from clinical trials that have investigated micronutrient and molecular targeting interventions. Finally, we introduce the concept of green chemoprevention, interventions based upon whole plant foods or simple extracts that may represent a safe and cost-conscious option for the next generation of studies. As our scientific understanding of HNSCC reaches new levels, the field is poised to develop chemoprevention studies based on rigorous biological validation with accessibility to all affected individuals regardless of socioeconomic barriers. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Cancer chemoprevention and cancer preventive vaccines--a call to action: leaders of diverse stakeholder groups present strategies for overcoming multiple barriers to meet an urgent need.

    Science.gov (United States)

    Herberman, Ronald B; Pearce, Homer L; Lippman, Scott M; Pyenson, Bruce S; Alberts, David S

    2006-12-15

    The emerging field of cancer prevention through chemoprevention agents and cancer vaccines offers significant promise for reducing suffering and death from cancer. However, that promise may not be kept unless major barriers to progress are lowered or eliminated. Among the most significant barriers are the relatively small investment from government and industry in research and development of cancer preventive agents; a predominant emphasis of translational cancer research on therapeutic interventions for metastatic or advanced cancer; complexities of prevention trial design; a relatively uncharted Food and Drug Administration (FDA) approval process for preventive agents; insufficient public and patient understanding of the importance and potential for cancer preventive measures, with consequent unpredictable public and patient willingness to take preventive agents; an uncertain reimbursement from payors; and limitations in patent law, liability protection, and data package exclusivity that undermine the opportunity for recouping investment. Viewed individually or collectively, each of these barriers serves as a substantial deterrent to intellectual and financial investment by all sectors of the cancer community. In an effort to ultimately overcome these barriers, a Cancer Prevention Research Summit was assembled June 12-13, 2006 in Bethesda, Maryland, organized by C-Change with support from the AACR. The Summit brought together some 120 leaders from private, public, and not-for-profit entities, including cancer researchers and clinicians; federal health officials; regulatory agency representatives; pharmaceutical, biotech, and food industry leaders; patent attorneys; economists; public and private provider group executives; and advocates. Participants engaged in a detailed process to more carefully define the major barriers, identify potential solutions, and formulate initial priorities and recommendations for action. At the conclusion of this dialogue among

  6. Breast cancer chemopreventive and chemotherapeutic effects of Camellia Sinensis (green tea): an updated review

    OpenAIRE

    Rafieian-Kopaei, Mahmoud; Movahedi, Mino

    2017-01-01

    Introduction Camellia sinensis belongs to the plant family of Theaceae, native to East Asia, the Indian Subcontinent and Southeast Asia, but naturalized in many parts of the world. The aim of this study was to overview its anti-breast cancer chemopreventive and chemotherapeutic effects. This review article is aimed to overview breast cancer chemopreventive and chemotherapeutic effects of Camellia sinensis (green tea). Methods This review article was carried out by searching studies in PubMed,...

  7. Chemopreventive effects of Coltect, a novel dietary supplement, alone and in combination with 5-aminosalicylic acid in 1,2-dimethylhydrazine-induced colon cancer in rats

    OpenAIRE

    Aroch, Ilan; Kraus, Sarah; Naumov, Inna; Ron, Ehud; Shapira, Shiran; Kazanov, Dina; Giladi, Nis; Litvak, Alex; Lev-Ari, Shahar; Hallak, Aharon; Dotan, Iris; Shpitz, Baruch; Arber, Nadir

    2010-01-01

    Objectives: Coltect is a novel dietary supplement containing curcumin, green tea and selenomethionine. Previous reports have suggested that these agents can prevent colorectal cancer (CRC). The present study examined the chemopreventive effect of Coltect alone or combined with 5-aminosalicylic acid (5-ASA) using the 1,2-dimethylhydrazine (DMH) model in rats.

  8. Implications of Cancer Stem Cell Theory for Cancer Chemoprevention by Natural Dietary Compounds

    Science.gov (United States)

    Li, Yanyan; Wicha, Max S.; Schwartz, Steven J.; Sun, Duxin

    2011-01-01

    The emergence of cancer stem cell theory has profound implications for cancer chemoprevention and therapy. Cancer stem cells give rise to the tumor bulk through continuous self-renewal and differentiation. Understanding the mechanisms that regulate self-renewal is of greatest importance for discovery of anti-cancer drugs targeting cancer stem cells. Naturally-occurring dietary compounds have received increasing attention in cancer chemoprevention. The anti-cancer effects of many dietary components have been reported for both in vitro and in vivo studies. Recently, a number of studies have found that several dietary compounds can directly or indirectly affect cancer stem cell self-renewal pathways. Herein we review the current knowledge of most common natural dietary compounds for their impact on self-renewal pathways and potential effect against cancer stem cells. Three pathways (Wnt/β-catenin, Hedgehog, and Notch) are summarized for their functions in self-renewal of cancer stem cells. The dietary compounds, including curcumin, sulforaphane, soy isoflavone, epigallocatechin-3-gallate, resveratrol, lycopene, piperine, and vitamin D3, are discussed for their direct or indirect effect on these self-renewal pathways. Curcumin and piperine have been demonstrated to target breast cancer stem cells. Sulforaphane has been reported to inhibit pancreatic tumor initiating cells and breast cancer stem cells. These studies provide a basis for preclinical and clinical evaluation of dietary compounds for chemoprevention of cancer stem cells. This may enable us to discover more preventive strategies for cancer management by reducing cancer resistance and recurrence and improving patient survival. PMID:21295962

  9. Topical tretinoin, another failure in the pursuit of practical chemoprevention for non-melanoma skin cancer.

    Science.gov (United States)

    Wu, Peggy A; Stern, Robert S

    2012-06-01

    Given the high incidence of non-melanoma skin cancer (NMSC), a preventative intervention would be desirable. Except for regular sunscreen use, the quest for chemoprevention of NMSC in the general population has been unsuccessful. Weinstock et al. assessed the effects of 0.1% topical tretinoin on NMSC. Like earlier efforts at chemoprevention, this study failed to show therapeutic benefit. Future successful preventative strategies will likely rely on short-term, intermittent therapy or treatments used for other common indications.

  10. Breast Cancer Metabolism and Mitochondrial Activity: The Possibility of Chemoprevention with Metformin

    Directory of Open Access Journals (Sweden)

    Massimiliano Cazzaniga

    2015-01-01

    Full Text Available Metabolic reprogramming refers to the ability of cancer cells to alter their metabolism in order to support the increased energy request due to continuous growth, rapid proliferation, and other characteristics typical of neoplastic cells. It has long been believed that the increase of metabolic request was independent of the mitochondrial action but recently we know that mitochondrial activity together with metabolism plays a pivotal role in the regulation of the energy needed for tumor cell growth and proliferation. For these reasons the mitochondria pathways could be a new target for therapeutic and chemopreventive intervention. Metformin in particular is actually considered a promising agent against mitochondrial activity thanks to its ability to inhibit the mitochondrial complex I.

  11. Melanoma and nonmelanoma skin cancer chemoprevention: A role for nicotinamide?

    Science.gov (United States)

    Minocha, Rashi; Damian, Diona L; Halliday, Gary M

    2018-01-01

    Ultraviolet radiation (UVR) causes DNA damage in melanocytes by producing photolesions such as cyclobutane pyrimidine dimers and 8-oxo-7-hydrodeoxyguanosine. The production of reactive oxygen species by UVR also induces inflammatory cytokines that, together with the inherent immunosuppressive properties of UVR, propagate carcinogenesis. Nicotinamide (Vitamin B 3 ) enhances DNA repair, modulates the inflammatory environment produced by UVR, and reduces UV-induced immunosuppression. As nicotinamide reduces the incidence of actinic keratoses and nonmelanoma skin cancers in high-risk individuals and enhances repair of DNA damage in melanocytes, it is a promising agent for the chemoprevention of melanoma in high-risk populations. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Bladder urotoxicity pathophysiology induced by the oxazaphosphorine alkylating agents and its chemoprevention 

    Directory of Open Access Journals (Sweden)

    Łukasz Dobrek

    2012-09-01

    Full Text Available The use of oxazaphosphorines (cyclophosphamide, ifosfamide in the treatment of numerous neoplastic disorders is associated with their essential adverse effect in the form of hemorrhagic cystitis, which considerably limits the safety and efficacy of their pharmacotherapy. HC is a complex inflammatory response, induced by toxic oxazaphosphorines metabolite – acrolein with subsequent immunocompetetive cells activation and release of many proinflammatory agents. However, there are some chemoprotectant agents which help reduce the HC exacerbation.The article briefly discuses the mechanism of action of oxazaphosphorines, the pathophysiology of the hemorrhagic cystitis development and currently accepted chemopreventive agents, applied to the objective of urotoxicity amelioration. Moreover, the rationale for some phytopharmaceuticals administration as novel bladder protective compounds accompanying cyclophosphamide or ifosfamide therapy was also mentioned. 

  13. Chemoprevention of Skin Cancer Program Project | Division of Cancer Prevention

    Science.gov (United States)

    DESCRIPTION (provided by applicant): Skin cancer is the most common malignancy in the world. One out of three new cancers is a skin cancer. More than 1 million cases of non-melanoma skin cancer (NMSC) (basal cell carcinoma [BCC] and squamous cell cancers [SCC]) occur annually. While the incidence rates for non-melanoma skin cancers continue to rise, there continues to be a substantial impact on morbidity, health and health care costs. |

  14. Implications of cancer stem cell theory for cancer chemoprevention by natural dietary compounds.

    Science.gov (United States)

    Li, Yanyan; Wicha, Max S; Schwartz, Steven J; Sun, Duxin

    2011-09-01

    The emergence of cancer stem cell theory has profound implications for cancer chemoprevention and therapy. Cancer stem cells give rise to the tumor bulk through continuous self-renewal and differentiation. Understanding the mechanisms that regulate self-renewal is of greatest importance for discovery of anticancer drugs targeting cancer stem cells. Naturally occurring dietary compounds have received increasing attention in cancer chemoprevention. The anticancer effects of many dietary components have been reported for both in vitro and in vivo studies. Recently, a number of studies have found that several dietary compounds can directly or indirectly affect cancer stem cell self-renewal pathways. Herein we review the current knowledge of most common natural dietary compounds for their impact on self-renewal pathways and potential effect against cancer stem cells. Three pathways (Wnt/β-catenin, Hedgehog and Notch) are summarized for their functions in self-renewal of cancer stem cells. The dietary compounds, including curcumin, sulforaphane, soy isoflavone, epigallocatechin-3-gallate, resveratrol, lycopene, piperine and vitamin D(3), are discussed for their direct or indirect effect on these self-renewal pathways. Curcumin and piperine have been demonstrated to target breast cancer stem cells. Sulforaphane has been reported to inhibit pancreatic tumor-initiating cells and breast cancer stem cells. These studies provide a basis for preclinical and clinical evaluation of dietary compounds for chemoprevention of cancer stem cells. This may enable us to discover more preventive strategies for cancer management by reducing cancer resistance and recurrence and improving patient survival. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Molecular mechanisms for chemoprevention of colorectal cancer by natural dietary compounds.

    Science.gov (United States)

    Pan, Min-Hsiung; Lai, Ching-Shu; Wu, Jia-Ching; Ho, Chi-Tang

    2011-01-01

    Colorectal cancer is one of the major causes of cancer-related mortality in both men and women worldwide. This review focuses on preventing the initiation and promotion of neoplastic growth in colorectal cancer, particularly with natural dietary compounds. Chemoprevention is defined as the use of natural dietary compounds and/or synthetic substances that can delay, prevent, or even reverse the development of adenomas, as well as the progression from adenoma to carcinoma. The molecular mechanisms of their chemopreventive action are associated with the modulation of signaling cascades, gene expressions involved in the regulation of cell proliferation, differentiation, and apoptosis and the suppression of chronic inflammation, metastasis, and angiogenesis. Here, we summarize the currently known targets and signaling pathways whereby natural dietary compounds interfere with the development of colorectal cancer, and thus providing evidence for these substances in colonic cancer chemopreventive action. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Zileuton, 5-lipoxygenase inhibitor, acts as a chemopreventive agent in intestinal polyposis, by modulating polyp and systemic inflammation.

    Directory of Open Access Journals (Sweden)

    Elias Gounaris

    Full Text Available Leukotrienes and prostaglandins, products of arachidonic acid metabolism, sustain both systemic and lesion-localized inflammation. Tumor-associated Inflammation can also contribute to the pathogenesis of colon cancer. Patients with inflammatory bowel disease (IBD have increased risk of developing colon cancer. The levels of 5-lipoxygenase (5-LO, the key enzyme for leukotrienes production, are increased in colon cancer specimens and colonic dysplastic lesions. Here we report that Zileuton, a specific 5-LO inhibitor, can prevent polyp formation by efficiently reducing the tumor-associated and systemic inflammation in APCΔ468 mice.In the current study, we inhibited 5-LO by dietary administration of Zileuton in the APCΔ468 mouse model of polyposis and analyzed the effect of in vivo 5-LO inhibition on tumor-associated and systemic inflammation.Zileuton-fed mice developed fewer polyps and displayed marked reduction in systemic and polyp-associated inflammation. Pro-inflammatory cytokines and pro-inflammatory innate and adaptive immunity cells were reduced both in the lesions and systemically. As part of tumor-associated inflammation Leukotriene B4 (LTB4, product of 5-LO activity, is increased focally in human dysplastic lesions. The 5-LO enzymatic activity was reduced in the serum of Zileuton treated polyposis mice.This study demonstrates that dietary administration of 5-LO specific inhibitor in the polyposis mouse model decreases polyp burden, and suggests that Zileuton may be a potential chemo-preventive agent in patients that are high-risk of developing colon cancer.

  17. Pro-oxidant activity of dietary chemopreventive agents: an under-appreciated anti-cancer property [v1; ref status: indexed, http://f1000r.es/15s

    Directory of Open Access Journals (Sweden)

    Asfar S Azmi

    2013-06-01

    Full Text Available “Let food be thy medicine and medicine be thy food” was quoted by Hippocrates more than two thousand years ago and since ancient times the health benefits of different natural agents have been exploited. In modern research, the disease preventive benefits of many such natural agents, particularly dietary compounds and their derivatives, has been attributed to their well recognized activity as the regulators of redox state of the cell. Nevertheless, most of these studies have focused on their antioxidant activity. A large body of evidence indicates that a major fraction of these agents can elicit pro-oxidant (radical generating behavior which has been linked to their anti-cancer effects. This editorial provides an overview of the under-appreciated pro-oxidant activity of natural products, with a special focus on their ability to generate reactive oxygen species in the presence of transition metal ions, and discusses their possible use as cancer chemotherapeutic agents.

  18. Chemopreventive and immunomodulatory effects of Murraya koenigii aqueous extract on 4T1 breast cancer cell-challenged mice.

    Science.gov (United States)

    Yeap, Swee Keong; Abu, Nadiah; Mohamad, Nurul Elyani; Beh, Boon Kee; Ho, Wan Yong; Ebrahimi, Siamak; Yusof, Hamidah Mohd; Ky, Huynh; Tan, Sheau Wei; Alitheen, Noorjahan Banu

    2015-09-04

    The progression of breast cancer is increasing at an alarming rate, particularly in western countries. Meanwhile, the lower incidence in Asian countries could be attributed to the heavy incorporation of green leaves vegetables or spices in their diets. Murraya koenigii (MK) or often times known as curry leaves are common spice used mostly in tropical countries. Anti-inflammatory and chemopreventive effects of MK aqueous extract on 4T1 breast cancer cell-challenged mice were evaluated. Herein, cytotoxic activity of MK was first tested on 4T1 cells in vitroby MTT assay. Then, in vivo chemopreventive study was conducted where mice were fed with extracts prior to and after inducing the tumor (inoculation). Tumor size was monitored post-4T1 inoculation. At the end of experiment, histopathology of tumor sections, T cell immunophenotyping, tumor nitric oxide level, serum cytokine level and qPCR analysis on expression of iNOS, iCAM, NF-kB and c-MYC were performed. MK reduced the tumors' size and lung metastasis aside from inhibited the viability of 4T1 cells in vitro. Furthermore, it decreased the level of nitric oxide and inflammation-related cytokines and genes, including iNOS, iCAM, NF-kB and c-MYC. The results propose that, MK managed to inhibit the progression of tumor via immunostimulatory effect and inflammatory reaction within the tumor samples. This suggests that MKconsumption could be a savior in the search of new chemopreventive agents.

  19. Relationships between pulmonary micro-RNA and proteome profiles, systemic cytogenetic damage and lung tumors in cigarette smoke-exposed mice treated with chemopreventive agents.

    Science.gov (United States)

    Izzotti, Alberto; Balansky, Roumen; D'Agostini, Francesco; Longobardi, Mariagrazia; Cartiglia, Cristina; La Maestra, Sebastiano; Micale, Rosanna T; Camoirano, Anna; Ganchev, Gancho; Iltcheva, Marietta; Steele, Vernon E; De Flora, Silvio

    2013-10-01

    Assessing the correlation between molecular endpoints and cancer induction or prevention aims at validating the use of intermediate biomarkers. We previously developed murine models that are suitable to detect both the carcinogenicity of mainstream cigarette smoke (MCS) and the induction of molecular alterations. In this study, we used 931 Swiss mice in two parallel experiments and in a preliminary toxicity study. The chemopreventive agents included vorinostat, myo-inositol, bexarotene, pioglitazone and a combination of bexarotene and pioglitazone. Pulmonary micro-RNAs and proteins were evaluated by microarray analyses at 10 weeks of age in male and female mice, either unexposed or exposed to MCS since birth, and either untreated or receiving each one of the five chemopreventive regimens with the diet after weaning. At 4 months of age, the frequency of micronucleated normochromatic erythrocytes was evaluated. At 7 months, the lungs were subjected to standard histopathological analysis. The results showed that exposure to MCS significantly downregulated the expression of 79 of 694 lung micro-RNAs (11.4%) and upregulated 66 of 1164 proteins (5.7%). Administration of chemopreventive agents modulated the baseline micro-RNA and proteome profiles and reversed several MCS-induced alterations, with some intergender differences. The stronger protective effects were produced by the combination of bexarotene and pioglitazone, which also inhibited the MCS-induced clastogenic damage and the yield of malignant tumors. Pioglitazone alone increased the yield of lung adenomas. Thus, micro-RNAs, proteins, cytogenetic damage and lung tumors were closely related. The molecular biomarkers contributed to evaluate both protective and adverse effects of chemopreventive agents and highlighted the mechanisms involved.

  20. Dietary factors and cancer chemoprevention: An overview of obesity-related malignancies

    Directory of Open Access Journals (Sweden)

    Murthy N

    2009-01-01

    Full Text Available Obesity is a growing health problem in developed nations and in countries that are in the process of westernization like India. Obesity is linked with several health disorders such as hypertension and cardiovascular diseases, Type 2 diabetes, dyslipidemia and certain cancers. Currently, obesity-related malignancies, e.g., cancers of the breast, prostate and colon are the leading cancers in the industrialized societies. An increased amount of fat or adipose tissue in an overweight or obese person probably influences the development of cancer by releasing several hormone-like factors or adipokines. The majority of adipokines are pro-inflammatory, which promote pathological conditions like insulin resistance and cancer. On the other hand, many recent studies have shown that adiponectin, an anti-inflammatory adipokine, has anti-cancer and insulin-sensitizing effects. Adiponectin exerts its physiological functions chiefly by activation of AMP kinase via adiponectin receptors. Interestingly, several fruits and vegetables may contain adiponectin-like molecules or may increase the biosynthesis of adiponectin in our body. Studies on adiponectin analogues or adiponectin receptor agonists are a promising area of cancer chemoprevention research. In general, fruits and vegetables contain various dietary substances such as vitamins, minerals (like calcium and selenium, fiber and phytochemicals or phenolic compounds (like flavonoids and vanilloids, which may act as anti-cancer agents. Similarly, several dietary constituents including phytochemicals may have anti-obesity effects. Consumption of such dietary compounds along with caloric restriction and physical activity may be helpful in preventing obesity-related cancers. For this review article, we searched PubMed primarily to get the relevant literature.

  1. Combination Chemoprevention with Diclofenac, Calcipotriol and Difluoromethylornithine Inhibits Development of Non-melanoma Skin Cancer in Mice

    DEFF Research Database (Denmark)

    Pommergaard, Hans-Christian; Burcharth, Jakob; Rosenberg, Jacob

    2013-01-01

    Background/Aim: With increasing incidence of non-melanoma skin cancer (NMSC), focus on chemoprevention of this disease is growing. The aim of this study was to evaluate topical combination therapies as chemoprevention of UV radiation-induced tumors in a mouse model.......Background/Aim: With increasing incidence of non-melanoma skin cancer (NMSC), focus on chemoprevention of this disease is growing. The aim of this study was to evaluate topical combination therapies as chemoprevention of UV radiation-induced tumors in a mouse model....

  2. Estrogen- and stress-induced DNA damage in breast cancer and chemoprevention with dietary flavonoid.

    Science.gov (United States)

    Yasuda, Michiko T; Sakakibara, Hiroyuki; Shimoi, Kayoko

    2017-01-01

    Breast cancer is one of the most commonly diagnosed female cancers and a leading cause of cancer-related death in women. Multiple factors are responsible for breast cancer and heritable factors have received much attention. DNA damage in breast cancer is induced by prolonged exposure to estrogens, such as 17β-estradiol, daily social/psychological stressors, and environmental chemicals such as polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HCAs). DNA damage induced by estrogen and stress is an important factor in the pathogenesis and development of breast cancer and is now recognized as a critical provision for chemoprevention of breast cancer. In this review, we summarize the relationships between estrogen- and stress-induced DNA damage with regard to the pathogenesis and development of breast cancer. We also discuss recent investigations into chemoprevention using dietary flavonoids such as quercetin and isoflavones.

  3. Adlay (薏苡 yì yĭ; “soft-shelled job's tears”; the seeds of Coix lachryma-jobi L. var. ma-yuen Stapf is a Potential Cancer Chemopreventive Agent toward Multistage Carcinogenesis Processes

    Directory of Open Access Journals (Sweden)

    Ching-Chuan Kuo, Ph.D.

    2012-10-01

    Full Text Available Adlay (薏苡 yì yĭ; “soft-shelled job’s tears”, the seeds of Coix lachryma-jobi L. var. ma-yuen Stapf is a grass crop that has long been used in traditional Chinese medicine (TCM and as a nourishing food in China for the treatment of warts, chapped skin, rheumatism, neuralgia, inflammatory, and neoplastic diseases. In addition, adlay also has been said to have stomachic, diuretic, antipholgistic, anodynic, and antispasmodic effects. Carcinogenesis is a multistage process that begins with exposure of viruses or chemicals that are found in the environment. Chemoprevention refers to the use of natural or synthetic, non-toxic chemical substances to reverse, repress, or prevent carcinogenesis. In this review, we summarize recent research attempting to study the chemopreventive blocking and suppressing potential of adlay and its active components in scavenging electrophiles and reactive oxygen species, antimutagenicity, enhancing Nrf2-mediated detoxification and antioxidant effect, altering carcinogen metabolism, suppressing proliferation, decreasing inflammation, and enhancing antitumor immunity. In addition, several active components with diverse chemopreventive properties have been also mentioned in this review article.

  4. Adlay ( yì yĭ; "soft-shelled job's tears"; the seeds of Coix lachryma-jobi L. var. ma-yuen Stapf) is a Potential Cancer Chemopreventive Agent toward Multistage Carcinogenesis Processes.

    Science.gov (United States)

    Kuo, Ching-Chuan; Chen, Huang-Hui; Chiang, Wenchang

    2012-10-01

    Adlay ( yì yĭ "soft-shelled job's tears", the seeds of Coix lachryma-jobi L. var. ma-yuen Stapf) is a grass crop that has long been used in traditional Chinese medicine (TCM) and as a nourishing food in China for the treatment of warts, chapped skin, rheumatism, neuralgia, inflammatory, and neoplastic diseases. In addition, adlay also has been said to have stomachic, diuretic, antipholgistic, anodynic, and antispasmodic effects. Carcinogenesis is a multistage process that begins with exposure of viruses or chemicals that are found in the environment. Chemoprevention refers to the use of natural or synthetic, non-toxic chemical substances to reverse, repress, or prevent carcinogenesis. In this review, we summarize recent research attempting to study the chemopreventive blocking and suppressing potential of adlay and its active components in scavenging electrophiles and reactive oxygen species, antimutagenicity, enhancing Nrf2-mediated detoxification and antioxidant effect, altering carcinogen metabolism, suppressing proliferation, decreasing inflammation, and enhancing antitumor immunity. In addition, several active components with diverse chemopreventive properties have been also mentioned in this review article.

  5. Adlay (薏苡 yì yĭ; “soft-shelled job's tears”; the seeds of Coix lachryma-jobi L. var. ma-yuen Stapf) is a Potential Cancer Chemopreventive Agent toward Multistage Carcinogenesis Processes

    Science.gov (United States)

    Kuo, Ching-Chuan; Chen, Huang-Hui; Chiang, Wenchang

    2012-01-01

    Adlay (薏苡 yì yĭ “soft-shelled job's tears”, the seeds of Coix lachryma-jobi L. var. ma-yuen Stapf) is a grass crop that has long been used in traditional Chinese medicine (TCM) and as a nourishing food in China for the treatment of warts, chapped skin, rheumatism, neuralgia, inflammatory, and neoplastic diseases. In addition, adlay also has been said to have stomachic, diuretic, antipholgistic, anodynic, and antispasmodic effects. Carcinogenesis is a multistage process that begins with exposure of viruses or chemicals that are found in the environment. Chemoprevention refers to the use of natural or synthetic, non-toxic chemical substances to reverse, repress, or prevent carcinogenesis. In this review, we summarize recent research attempting to study the chemopreventive blocking and suppressing potential of adlay and its active components in scavenging electrophiles and reactive oxygen species, antimutagenicity, enhancing Nrf2-mediated detoxification and antioxidant effect, altering carcinogen metabolism, suppressing proliferation, decreasing inflammation, and enhancing antitumor immunity. In addition, several active components with diverse chemopreventive properties have been also mentioned in this review article. PMID:24716141

  6. Evaluating the potential cancer chemopreventive efficacy of two different solvent extracts of Seriphidium herba-alba in vitro

    Directory of Open Access Journals (Sweden)

    Mahmoud Mohamed Mokhtar

    2017-06-01

    Full Text Available Cancer is the second leading cause of death world-wide. One of the most important medical practices of the 21st century is the chemoprevention of cancer. For a long history, it has been accepted that plants could prevent and exert suitable anti-carcinogenic effects for multiple types of cancers. Seriphidium herba-alba family Asteraceae has been used in the folk medicine by many cultures for treatment of various ailments since ancient times. In the current research we were aimed to evaluate the cancer chemopreventive activity of two crude extracts of S. herba-alba, methylene chloride extract and methanol extract on two cell lines: Human breast cancer cells (MCF-7 and human hepatocellular carcinoma cells (Hep-G2. Assessment of cytotoxicity using methyl thiazole tetrazolium (MTT assay indicated that both extracts exhibit poor cytotoxicity with half maximal inhibitory concentration (IC50 >20 µg/mL. Assessment of glutathione-S-transferases (GSTs activity (spectrophotometrically showed statistically significant enhancement of enzyme activity after treatment with three different doses of methylene chloride extract and glutathione (GSH concentrations were decreased. Analysis of cell mode of death by Ethidium bromide/Acridine orange (EB/AO staining revealed that the dominant mode of death in MCF-7 cells was apoptosis. Assessment of vascular endothelial growth factor (VEGF and platelets derived growth factor (PDGFBB using ELISA showed that VEGF and PDGFBB levels were statistically significant decreased. In Conclusion: both extracts may be cancer chemopreventive agents since they had tumor anti-initiating, and anti-promoting activity.

  7. Benefit/Risk Assessment for Breast Cancer Chemoprevention With Raloxifene or Tamoxifen for Women Age 50 Years or Older

    Science.gov (United States)

    Freedman, Andrew N.; Yu, Binbing; Gail, Mitchell H.; Costantino, Joseph P.; Graubard, Barry I.; Vogel, Victor G.; Anderson, Garnet L.; McCaskill-Stevens, Worta

    2011-01-01

    Purpose The Study of Tamoxifen and Raloxifene (STAR) demonstrated that raloxifene was as effective as tamoxifen in reducing the risk of invasive breast cancer (IBC) in postmenopausal women and had lower risks of thromboembolic events, endometrial cancer, and cataracts but had a nonstatistically significant higher risk of noninvasive breast cancer. There is a need to summarize the risks and benefits of these agents. Patients and Methods Baseline incidence rates of IBC and other health outcomes, absent raloxifene and tamoxifen, were estimated from breast cancer chemoprevention trials; the Surveillance, Epidemiology and End Results Program; and the Women's Health Initiative. Effects of raloxifene and tamoxifen were estimated from STAR and the Breast Cancer Prevention Trial. We assigned weights to health outcomes to calculate the net benefit from raloxifene compared with placebo and tamoxifen compared with placebo. Results Risks and benefits of treatment with raloxifene or tamoxifen depend on age, race, breast cancer risk, and history of hysterectomy. Over a 5-year period, postmenopausal women with an intact uterus had a better benefit/risk index for raloxifene than for tamoxifen. For postmenopausal women without a uterus, the benefit/risk ratio was similar. The benefits and risks of raloxifene and tamoxifen are described in tables that can help identify groups of women for whom the benefits outweigh the risks. Conclusion We developed a benefit/risk index to quantify benefits from chemoprevention with tamoxifen or raloxifene. This index can complement clinical evaluation in deciding whether to initiate chemoprevention and in comparing the benefits and risks of raloxifene versus tamoxifen. PMID:21537036

  8. Chemoprevention of breast cancer in the older patient.

    Science.gov (United States)

    Minton, S E

    2000-02-01

    Age is the most important risk factor for the development of breast cancer. The risk of breast cancer continues to increase in American women until the age of 80 years. A family history of breast cancer helps identify those who possibly have the highest risk of developing breast cancer; however, most women who develop breast cancer do not have a first-degree relative with a history of breast cancer. Currently, the Gail model is a commonly used model to identify risk, and this model has now been validated in several populations of women undergoing screening for breast cancer. The first large-scale breast cancer prevention trial investigating the preventive effects of tamoxifen has demonstrated a decrease in the development of breast cancer by almost 50% in the women in the tamoxifen treatment arm as compared with those receiving placebo. The NSABP P-1 trial was the largest of the three tamoxifen breast cancer prevention trials and had the greatest power to detect a difference between the two treatment groups in breast cancer events. This trial also included the largest percentage of postmenopausal women. It is unclear why the Italian and Royal Marsden Hospital trials had negative results regarding the preventive effects of tamoxifen. These two trials were strikingly different from the NSABP P-1 trial, however, and they included a different population of women. The issues surrounding the use of HRT for treatment of hot flashes in the Italian and Royal Marsden Hospital trials adds to the controversy concerning the negative results of these trials. The new SERM, raloxifene, has shown promise in preliminary studies as a preventive agent for breast cancer. The STAR trial will open soon and will evaluate the efficacy of raloxifene in preventing breast cancer in a prospective fashion, comparing its efficacy with tamoxifen treatment. Other endpoints will evaluate side effects such as menopausal symptoms, endometrial cancer, thromboembolic events, and benefits regarding

  9. Breast cancer chemopreventive and chemotherapeutic effects of Camellia Sinensis (green tea): an updated review.

    Science.gov (United States)

    Rafieian-Kopaei, Mahmoud; Movahedi, Mino

    2017-02-01

    Camellia sinensis belongs to the plant family of Theaceae, native to East Asia, the Indian Subcontinent and Southeast Asia, but naturalized in many parts of the world. The aim of this study was to overview its anti-breast cancer chemopreventive and chemotherapeutic effects. This review article is aimed to overview breast cancer chemopreventive and chemotherapeutic effects of Camellia sinensis (green tea). This review article was carried out by searching studies in PubMed, Medline, Web of Science, and IranMedex databases. The initial search strategy identified around 108 references. In this study, 68 studies were accepted for further screening, and met all our inclusion criteria [in English, full text, chemopreventive and chemotherapeutic effects of Camellia sinensis and dated mainly from the year 1999 to 2016. The search terms were Camellia sinensis, chemopreventive, chemotherapeutic properties, pharmacological effects. The result of this study suggested that the catechin available in Camellia sinensis has properties which can prevent and treat breast cancer. It has also been shown to inhibit proliferation of breast cancer cells and to block carcinogenesis. It was found that increased Camellia sinensis consumption may lower the risk of breast cancer. Camellia sinensis intake was shown to reduce the risk of breast cancer incidence. In addition, potential breast cancer chemopreventive effect of Camellia sinensis both in vivo and in vitro was highly confirmed. However, the evidence of low effect and no effect was observed. More clinical trial studies are needed to prove its anti-breast cancer activity decisively. Camellia sinensis is broadly utilized as a part of customary medication since antiquated time because of its cost adequacy, and fewer reaction properties. The studies demonstrated anti-breast cancer activity of Camellia sinensis and its component by adjusting cell signaling pathways such as angiogenesis, apoptosis, and transcription factor. Furthermore

  10. Potential Chemopreventive Agents Based on the Structure of the Lead Compound 2-Bromo-1-hydroxyphenazine, Isolated from Streptomyces sp., Strain CNS284

    Science.gov (United States)

    Conda-Sheridan, Martin; Marler, Laura; Park, Eun-Jung; Kondratyuk, Tamara P.; Jermihov, Katherine; Mesecar, Andrew D.; Pezzuto, John M.; Asolkar, Ratnakar N.; Fenical, William; Cushman, Mark

    2010-01-01

    The isolation of 2-bromo-1-hydroxyphenazine from a marine Streptomyces sp., strain CNS284, and its activity against NFκB, suggested that a short and flexible route for the synthesis of this metabolite and a variety of phenazine analogues be developed. Numerous phenazines were subsequently prepared and evaluated as inducers of quinone reductase 1 (QR1) and inhibitors of quinone reductase 2 (QR2), NF-κB, and inducible nitric oxide synthase (iNOS). Several of the active phenazine derivatives displayed IC50 values vs. QR1 induction and QR2 inhibition in the nanomolar range, suggesting they may find utility as cancer chemopreventive agents. PMID:21105712

  11. Potential chemopreventive agents based on the structure of the lead compound 2-bromo-1-hydroxyphenazine, isolated from Streptomyces species, strain CNS284.

    Science.gov (United States)

    Conda-Sheridan, Martin; Marler, Laura; Park, Eun-Jung; Kondratyuk, Tamara P; Jermihov, Katherine; Mesecar, Andrew D; Pezzuto, John M; Asolkar, Ratnakar N; Fenical, William; Cushman, Mark

    2010-12-23

    The isolation of 2-bromo-1-hydroxyphenazine from a marine Streptomyces species, strain CNS284, and its activity against NF-κB, suggested that a short and flexible route for the synthesis of this metabolite and a variety of phenazine analogues should be developed. Numerous phenazines were subsequently prepared and evaluated as inducers of quinone reductase 1 (QR1) and inhibitors of quinone reductase 2 (QR2), NF-κB, and inducible nitric oxide synthase (iNOS). Several of the active phenazine derivatives displayed IC₅₀ values vs QR1 induction and QR2 inhibition in the nanomolar range, suggesting that they may find utility as cancer chemopreventive agents.

  12. Antimutagenic constituents of adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) with potential cancer chemopreventive activity.

    Science.gov (United States)

    Chen, Huang-Hui; Chiang, Wenchang; Chang, Jang-Yang; Chien, Ya-Lin; Lee, Ching-Kuo; Liu, Ko-Jiunn; Cheng, Yen-Ting; Chen, Ting-Fang; Kuo, Yueh-Hsiung; Kuo, Ching-Chuan

    2011-06-22

    Adlay has long been used in traditional Chinese medicine and as a nourishing food. The acetone extract of adlay hull had previously been demonstrated to possess potent antimutagenic activity. The aims of this study were to identify the antimutagenic constituents from adlay hull by using Ames antimutagenic activity-guide isolation procedures and to investigate their chemopreventive efficacies in cultured cells. The results demonstrated that six compounds showing great antimutagenic activity were identified by spectroscopic methods and by comparison with authentic samples to be p-hydroxybenzaldehyde, vanillin, syringaldehyde, trans-coniferylaldehyde, sinapaldehyde, and coixol. Two of them, trans-coniferylaldehyde and sinapaldehyde, exhibit relatively potent scavenging of DPPH radicals, inhibit TPA stimulated superoxide anion generation in neutrophil-like leukocytes, and induce Nrf2/ARE-driven luciferase activity in HSC-3 cells. Moreover, trans-coniferylaldehyde possesses cytoprotective efficacy against tert-butyl hydroperoxide-induced DNA double-strand breaks in cultured cells, and the chemopreventive potency induced by trans-coniferylaldehyde may be through the activation of kinase signals, including p38, ERK1/2, JNK, MEK1/2, and MSK1/2. In summary, we first identified six antimutagenic constituents from adlay hull. Among them, trans-coniferylaldehyde would be a highly promising agent for cancer chemoprevention and merits further investigation.

  13. Lung-cancer chemoprevention by induction of synthetic lethality in mutant KRAS premalignant cells in vitro and in vivo

    National Research Council Canada - National Science Library

    Huang, Shaoyi; Ren, Xiaoyang; Wang, Lai; Zhang, Ling; Wu, Xiangwei

    2011-01-01

    .... These data underscore the great need for effective chemoprevention of this cancer. Mutations and activation of KRAS occur frequently in, and are thought to be a primary driver of the development of, non-small cell lung cancers (NSCLC...

  14. Cancer Chemoprevention by Phytochemicals: Nature’s Healing Touch

    Directory of Open Access Journals (Sweden)

    Haseeb Zubair

    2017-03-01

    Full Text Available Phytochemicals are an important part of traditional medicine and have been investigated in detail for possible inclusion in modern medicine as well. These compounds often serve as the backbone for the synthesis of novel therapeutic agents. For many years, phytochemicals have demonstrated encouraging activity against various human cancer models in pre-clinical assays. Here, we discuss select phytochemicals—curcumin, epigallocatechin-3-gallate (EGCG, resveratrol, plumbagin and honokiol—in the context of their reported effects on the processes of inflammation and oxidative stress, which play a key role in tumorigenesis. We also discuss the emerging evidence on modulation of tumor microenvironment by these phytochemicals which can possibly define their cancer-specific action. Finally, we provide recent updates on how low bioavailability, a major concern with phytochemicals, is being circumvented and the general efficacy being improved, by synthesis of novel chemical analogs and nanoformulations.

  15. Tannins, xenobiotic metabolism and cancer chemoprevention in experimental animals.

    Science.gov (United States)

    Nepka, C; Asprodini, E; Kouretas, D

    1999-01-01

    Tannins are plant polyphenolic compounds that are contained in large quantities in food and beverages (tea, red wine, nuts, etc.) consumed by humans daily. It has been shown that various tannins exert broad cancer chemoprotective activity in a number of animal models. This review summarizes the recent literature regarding both the mechanisms involved, and the specific organ cancer models used in laboratory animals. An increasing body of evidence demonstrates that tannins act as both anti-initiating and antipromoting agents. In view of the fact that tannins may be of valid medicinal efficacy in human clinical trials, the present review attempts to integrate results from animal studies, and considers their possible application in humans.

  16. Chemopreventive Effects of the p53-Modulating Agents CP-31398 and Prima-1 in Tobacco Carcinogen-Induced Lung Tumorigenesis in A/J Mice

    Directory of Open Access Journals (Sweden)

    Chinthalapally V. Rao

    2013-09-01

    Full Text Available Lung cancer is the leading cause of cancer deaths worldwide. Expression of the p53 tumor suppressor protein is frequently altered in tobacco-associated lung cancers. We studied chemopreventive effects of p53-modulating agents, namely, CP-31398 and Prima-1, on 4-(methylnitrosamino-1-(3-pyridyl-1-butanone (NNK-induced lung adenoma and adenocarcinoma formation in female A/J mice. Seven-week-old mice were treated with a single dose of NNK (10 µmol/mouse by intraperitoneal injection and, 3 weeks later, were randomized to mice fed a control diet or experimental diets containing 50 or 100 ppm CP-31398 or 150 or 300 ppm Prima-1 for either 17 weeks (10 mice/group or 34 weeks (15 mice/group to assess the efficacy against lung adenoma and adenocarcinoma. Dietary feeding of 50 or 100 ppm CP-31398 significantly suppressed (P < .0001 lung adenocarcinoma by 64% and 73%, respectively, after 17 weeks and by 47% and 56%, respectively, after 34 weeks. Similarly, 150 or 300 ppm Prima-1 significantly suppressed (P < .0001 lung adenocarcinoma formation by 56% and 62%, respectively, after 17 weeks and 39% and 56%, respectively, after 34 weeks. Importantly, these results suggest that both p53 modulators cause a delay in the progression of adenoma to adenocarcinoma. Immunohistochemical analysis of lung tumors from mice exposed to p53-modulating agents showed a significantly reduced tumor cell proliferation and increased accumulation of wild-type p53 in the nucleus. An increase in p21- and apoptotic-positive cells was also observed in lung tumors of mice exposed to p53-modulating agents. These results support a chemopreventive role of p53-modulating agents in tobacco carcinogen-induced lung adenocarcinoma formation.

  17. Cancer chemopreventive potential of aromathecins and phenazines, novel natural product derivatives.

    Science.gov (United States)

    Marler, Laura; Conda-Sheridan, Martin; Cinelli, Maris A; Morrell, Andrew E; Cushman, Mark; Chen, Lian; Huang, Ke; Van Breemen, Richard; Pezzuto, John M

    2010-12-01

    In the search for agents with cancer chemopreventive potential, 14-chloromethyl-12H-5,11a-diazadibenzo[b,h]fluoren-11-one (compound 1), originally synthesized as a potential topoisomerase I inhibitor, and 2,4-dibromo-1-hydroxyphenazine (compound 2), an analog of a substance found in the marine bacteria Streptomyces CNS284, were found to significantly enhance NADP(H):quinone oxidoreductase 1 (QR1), glutathione S-transferase (GST), and glutathione (GSH) levels in cell culture. However, following a short-term absorption study, analyses of livers from the treatment groups did not reveal a significant increase in QR1 or GST activity, or GSH levels. This was consistent with RT-PCR analyses of tissue samples. The compounds were absorbed, as judged by LC/MS analyses of serum and tissue samples, although levels were well below the concentrations required to mediate in vitro responses. Metabolites of compound 2 formed in vitro by human liver microzones were characterized using high resolution tandem mass spectrometry. In sum, the in vivo activity of these compounds appears to be diminished by low bioavailability, but this experimental approach indicates the importance of systematic biomarker investigation.

  18. Pancreatic Cancer: Molecular, Biochemical, Chemopreventive, and Therapeutic Aspects

    Directory of Open Access Journals (Sweden)

    Juan Iovanna

    2010-01-01

    Full Text Available Pancreatic cancer (PC is the fourth leading cause of cancer death, with a median survival of 6 months and a dismal 5-year survival rate of 3–5%, a figure which has remained relatively unchanged over the past 25 years. PC is one of the most difficult diseases to treat due to late initial diagnosis and to resistance to the usual treatments. The presence of occult or clinical metastases at the time of diagnosis, together with the lack of effective chemotherapies, contributes to the high mortality in patients with PC. Its lethal nature stems from its propensity to disseminate rapidly to the lymphatic system and distant organs. Yet, understanding and stopping metastasis may prove to be one of the great potential strategies of treating PC. There is a dire need for the design of new and targeted therapeutic strategies that can overcome the drug resistance and improve the clinical outcome for patients diagnosed with the illness. The knowledge of the molecular aspects of PC is very important, and it is likely to be helpful in the design of newer drugs and the molecular selection of existing agents for targeted therapy. The inhibition of signal pathways can be carried out not only by small molecules, able to bind to selected regions of the target protein, but also by using large molecules as antibodies. The pathway to successful new therapies has been inhibited because of the rapidity with which agents tend to move into randomized, controlled trials without the extensive early testing necessary to optimize treatment regimens. However, lessons have been learned and our collective research effort has generated a substantial platform of knowledge from which further work will spring. The bioavailability of compounds such as antisense oligonucleotides and siRNAs in humans remains a big hurdle, which will require further improvement of gene-delivery strategies. Finally, the long-term goal of the therapy individualization for patients is possible if factors

  19. Infectious Agents and Cancer

    African Journals Online (AJOL)

    Hepatocellular carcinoma. Cervical cancer, other anogenital ... The expression of the E6 and E7 open reading frames (ORFs) from high .... protein CagA [3 5]. They also elaborate urease, alcohol dehydrogenase and mucolytic factors. All these agents contribute to the development of cancer following H. pylori infection.

  20. The chemopreventive action of equol enantiomers in a chemically induced animal model of breast cancer

    Science.gov (United States)

    Brown, Nadine M.; Belles, Carrie A.; Lindley, Stephanie L.; Zimmer-Nechemias, Linda D.; Zhao, Xueheng; Witte, David P.; Kim, Mi-Ok; Setchell, Kenneth D.R.

    2010-01-01

    We describe for the first time the chemopreventive effects of S-(−)equol and R-(+)equol, diastereoisomers with contrasting affinities for estrogen receptors (ERs). S-(−)equol, a ligand for ERβ, is an intestinally derived metabolite formed by many humans and by rodents consuming diets containing soy isoflavones. Whether the well-documented chemopreventive effect of a soy diet could be explained by equol's action was unclear because neither diastereoisomers had been tested in animal models of chemoprevention. Sprague–Dawley rats (n = 40–41 per group) were fed a soy-free AIN-93G diet or an AIN-93G diet supplemented with 250 mg/kg of S-(−)equol or R-(+)equol beginning day 35. On day 50, mammary tumors were induced by dimethylbenz[a]anthracene and thereafter, animals were palpated for number and location of tumors. On day 190, animals were killed and mammary tumors were removed and verified by histology, and the degree of invasiveness and differentiation was determined. S-(−)equol and R-(+)equol plasma concentrations measured on days 35, 100 and 190 by tandem mass spectrometry confirmed diet compliance and no biotransformation of either diastereoisomer. In this model, S-(−)equol had no chemopreventive action, nor was it stimulatory. In contrast, R-(+)equol compared with Controls reduced palpable tumors (P = 0.002), resulted in 43% fewer tumors (P = 0.004), increased tumor latency (88.5 versus 66 days, P = 0.003), and tumors were less invasive but showed no difference in pattern grade or mitosis. Both enantiomers had no effect on absolute uterine weight but caused a significant reduction in body weight gain. In conclusion, the novel finding that the unnatural enantiomer, R-(+)equol, was potently chemopreventive warrants investigation of its potential for breast cancer prevention and treatment. PMID:20110282

  1. Breast cancer chemoprevention by dietary natural phenolic compounds: specific epigenetic related molecular targets.

    Science.gov (United States)

    Pan, Min-Hsiung; Chiou, Yi-Siou; Chen, Li-Hua; Ho, Chi-Tang

    2015-01-01

    Breast cancer is a systemic malignant disease that is a major cause of cancer-related death among women worldwide. Recently, multiple lines of evidence from epidemiologic studies have suggested that epigenetic and genetic changes are involved in breast cancer development. In breast cancer patients, hormone receptor status, breast cancer stem-like cell population, and tumor microenvironment are reflective of breast cancer progression, drug resistance, and tumor recurrence. Strong relationships between a phytochemical-rich diet and a reversal of epigenetic alterations and/or modulated signaling pathways of carcinogenesis (initiation, promotion, and progression) suggest a potential approach for preventing breast cancer. Additionally, dietary consumption of natural phenolic compounds containing phytoestrogen properties exerts beneficial effects in breast cancer chemoprevention. In this review, we summarize the specific chemopreventive targets of representative phenolic compounds with an emphasis on their efficacy at interfering with epigenetic event related hormonal and nonhormonal signaling cascades that are responsible for multistage breast carcinogenesis. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. In vitro and In vivo Studies on Stilbene Analogs as Potential Treatment Agents for Colon Cancer

    Science.gov (United States)

    Based upon the potential of resveratrol as a cancer chemopreventive agent, 27 stilbenes analogs were synthesized and tested against colon cancer cell line HT-29. Among these compounds, amino derivative (Z)-4-(3,5-dimethoxystyryl) aniline (4), (Z)-methyl 4-(3,5-dimethoxystyryl) benzoate (6) and (Z)-1...

  3. Protection against aflatoxin B1-induced hepatic toxicity as short-term screen of cancer chemopreventive dithiolethiones.

    Science.gov (United States)

    Maxuitenko, Y Y; Curphey, T J; Kensler, T W; Roebuck, B D

    1996-08-01

    Dithiolethiones are an important class of cancer chemopreventive agents. More than 50 new dithiolethione analogs were synthesized for structure-activity studies. Using selected dithiolethiones, studies were designed to measure protection against the hepatotoxicity of aflatoxin B1 (AFB1) and relate it to the protection against carcinogenicity. Young male F344 rats were pretreated with 0.1 or 0.3 mmol dithiolethiones/kg body wt and challenged with toxic doses of AFB1 (50 micrograms/100 g rat/day) on 2 successive days. One day later, the protection from hepatotoxicity was assessed by measuring serum hepatic enzymes, hepatic necrosis, and degree of bile duct cell proliferation. The ability of these dithiolethiones to prevent AFB1-induced tumorigenicity was assessed by quantifying the hepatic burden of putative preneoplastic lesions [placental glutathione S-transferase (GST-P)-positive foci]. Significant correlations (p bile duct cell proliferation, r = 0.933). These results imply that inhibition of hepatotoxicity affords protection against hepatocarcinogenicity. The extent of protection from acute hepatotoxicity offers a simple, short-term biological endpoint to screen dithiolethiones and related compounds for their chemopreventive properties.

  4. Role of a polyphenol-enriched preparation on chemoprevention of mammary carcinoma through cancer stem cells and inflammatory pathways modulation.

    Science.gov (United States)

    Vuong, Tri; Mallet, Jean-François; Ouzounova, Maria; Rahbar, Sam; Hernandez-Vargas, Hector; Herceg, Zdenko; Matar, Chantal

    2016-01-14

    Naturally occurring polyphenolic compounds from fruits, particularly from blueberries, have been reported to be significantly involved in cancer chemoprevention and chemotherapy. Biotransformation of blueberry juice by Serratia vaccinii increases its polyphenolic content and endows it with anti-inflammatory properties. This study evaluated the effect of a polyphenol-enriched blueberry preparation (PEBP) and its non-fermented counterpart (NBJ), on mammary cancer stem cell (CSC) development in in vitro, in vivo and ex vivo settings. Effects of PEBP on cell proliferation, mobility, invasion, and mammosphere formation were measured in vitro in three cell lines: murine 4T1 and human MCF7 and MDA-MB-231. Ex vivo mammosphere formation, tumor growth and metastasis observations were carried out in a BALB/c mouse model. Our research revealed that PEBP influence cellular signaling cascades of breast CSCs, regulating the activity of transcription factors and, consequently, inhibiting tumor growth in vivo by decreasing metastasis and controlling PI3K/AKT, MAPK/ERK, and STAT3 pathways, central nodes in CSC inflammatory signaling. PEBP significantly inhibited cell proliferation of 4T1, MCF-7 and MDA-MB-231. In all cell lines, PEBP reduced mammosphere formation, cell mobility and cell migration. In vivo, PEBP significantly reduced tumor development, inhibited the formation of ex vivo mammospheres, and significantly reduced lung metastasis. This study showed that polyphenol enrichment of a blueberry preparation by fermentation increases its chemopreventive potential by protecting mice against tumor development, inhibiting the formation of cancer stem cells and reducing lung metastasis. Thus, PEBP may represent a novel complementary alternative medicine therapy and a source for novel therapeutic agents against breast cancer.

  5. Breast cancer chemopreventive properties of pomegranate (Punica granatum) fruit extracts in a mouse mammary organ culture.

    Science.gov (United States)

    Mehta, R; Lansky, E P

    2004-08-01

    We previously reported anticancer effects of pomegranate extracts in human breast cancer cells in vitro and also chemopreventive activity of pomegranate fermented juice polyphenols (W) in a mouse mammary organ culture (MMOC). In the present study we decided to expand the MMOC investigations to also include an evaluation of the potential chemopreventive efficacy of a purified chromatographic peak of W (Peak B), and also of whole pomegranate seed oil. In brief, an MMOC was established according to a known method. For the first 10 days of culture, the glands were treated with pomegranate fermented juice polyphenols (W), a high-performance liquid chromatographic (HPLC) peak separated from W (peak B), or pomegranate seed oil (Oil, and on day 3, exposed to the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA), and for 10 days treated with the putative pomegranate chemopreventive. The glands were subsequently harvested and tumours counted by visual inspection. While W effected a 42% reduction in the number of lesions compared with control, peak B and pomegranate seed oil each effected an 87% reduction. The results highlight enhanced breast cancer preventive potential both for the purified compound peak B and for pomegranate seed oil, both greater than that previously reported for pomegranate fermented juice polyphenols.

  6. Characterization of chemopreventive agents from the dichloromethane extract of Eurycorymbus cavaleriei by liquid chromatography-ion trap mass spectrometry.

    Science.gov (United States)

    Cheng, Lin; Zhang, Xiaoyu; Zhang, Min; Zhang, Peng; Song, Zhihang; Ma, Zhongjun; Cheng, Yiyu; Qu, Haibin

    2009-06-12

    In the present study, we examined the potential chemopreventive activity of dichloromethane extract of Eurycorymbus cavaleriei by investigating the change of constitutions after incubation with glutathione (GSH). The major constitutions in the dichloromethane extract of E. cavaleriei were cumarin compounds and their cleavage pattern was examined by LC-MS-MS and the characteristic product ions at m/z 206 and 207 were helpful to determine the substitutions of coumarinolignoid compounds. The mechanism of conjugations of 5'-demethylaquillochin and its isomer with GSH was discussed and validated through analysis of the conjugations of reference compound 6-hydroxy-7-methoxycoumarin with GSH by LC-MS-MS and NMR spectrum. The relative ability to induce the detoxification enzyme, NAD(P)H:quinone oxidoreductase 1 (NQO1) of nine coumarin compounds was tested which also showed 5'-demethylaquillochin exhibited the most potential chemopreventive ability. These observations suggest that 5'-demethylaquillochin and its isomer from the dichloromethane extract of E. cavaleriei have potential as chemopreventive agents through induction of detoxification enzymes.

  7. Increased chemopreventive effect by combining arctigenin, green tea polyphenol and curcumin in prostate and breast cancer cells

    Science.gov (United States)

    Wang, Piwen; Wang, Bin; Chung, Seyung; Wu, Yanyuan; Henning, Susanne M.; Vadgama, Jaydutt V.

    2014-01-01

    The low bioavailability of most flavonoids limits their application as anti-carcinogenic agents in humans. A novel approach of treatment with a mixture of bioactive compounds that share molecular anti-carcinogenic targets may enhance the effect on these targets at low concentrations of individual compound, thereby overcoming the limitations of reduced bioavailability. We therefore investigated whether a combination of three natural products arctigenin (Arc), a novel anti-inflammatory lignan from the seeds of Arctium lappa, green tea polyphenol (−)-epigallocatechin gallate (EGCG) and curcumin (Cur) increases the chemopreventive potency of individual compounds. LNCaP prostate cancer and MCF-7 breast cancer cells were treated with 2–4 mg/L (about 5–10μM) Cur, 1μM Arc and 40μM EGCG alone or in combination for 48h. In both cell lines treatment with the mixture of Cur, Arc and EGCG synergistically increased the antiproliferative effect. In LNCaP cells both Arc and EGCG increased the pro-apoptotic effect of Cur. Whereas in MCF-7 cells Arc increased the cell apoptosis of Cur while EGCG enhanced cell cycle arrest of Cur at G0/G1 phase. The strongest effects on cell cycle arrest and apoptosis were achieved by combining all three compounds in both cell lines. The combination treatment significantly increased the ratio of Bax to Bcl-2 proteins, decreased the activation of NFκB, PI3K/Akt and Stat3 pathways and cell migration compared to individual treatment. These results warrant in vivo studies to confirm the efficacy of this novel regimen by combining Arc and EGCG with Cur to enhance chemoprevention in both prostate and breast cancer. PMID:25243063

  8. Chemoprevention for colon cancer: New opportunities, fact or fiction?

    NARCIS (Netherlands)

    Droste, J. S. Terhaar Sive; Tuynman, J. B.; van Dullemen, H. M.; Mulder, C. J. J.

    2006-01-01

    Colorectal cancer (CRC) is still a disease with a high incidence and mortality. Prevention of (pre-) cancerous lesions of CRC by endoscopic screening is promising, but costs are high and identification of high-risk populations is difficult. Since screening both average-risk and high-risk populations

  9. Epigenetic impact of dietary polyphenols in cancer chemoprevention: lifelong remodeling of our epigenomes.

    Science.gov (United States)

    Vanden Berghe, Wim

    2012-06-01

    Cancer, as one of the non-communicable diseases, remains one of the leading causes of death around the world. Recently, epigenetic changes in DNA methylation patterns at CpG sites (epimutations) or deregulated chromatin states of tumor promoting genes and noncoding RNAs emerged as major governing factors in tumor progression and cancer drug sensitivity. Furthermore, various environmental factors such as nutrition, behavior, stress, and toxins remodel our epigenomes lifelong in a beneficial or detrimental way. Since epigenetic marks (epimutations) are reversible in contrast to genetic defects, chemopreventive nutritional polyphenols (soy, genistein, resveratrol, catechin, curcumin) are currently evaluated for their ability to reverse adverse epigenetic marks in cancer (stem) cells to attenuate tumorigenesis-progression, prevent metastasis or sensitize for drug sensitivity. Although polyphenols in fruit and vegetables may help to reduce the risk of cancer, few protective effects have been firmly established, presumably because of inappropriate timing or dosing of diet exposure or due to confounding factors such as smoking and alcohol. In this review will discuss the possible epigenetic contributions of dietary polyphenols in cancer chemoprevention. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Curcumin and Other Polyphenolic Compounds in Head and Neck Cancer Chemoprevention

    Directory of Open Access Journals (Sweden)

    Philipp Baumeister

    2012-01-01

    Full Text Available Despite clear results of observational studies linking a diet rich in fruits and vegetables to a decreased cancer risk, large interventional trials evaluating the impact of dietary micronutrient supplementation, mostly vitamins, could not show any beneficial effects. Today it has become clear that a single micronutrient, given in supernutritional doses, cannot match cancer preventive effects of whole fruits and vegetables. In this regard polyphenols came into focus, not only because of their antioxidant potential but also because of their ability to interact with molecular targets within the cells. Because polyphenols occur in many foods and beverages in high concentration and evidence for their anticancer activity is best for tissues they can come into direct contact with, field cancerization predestines upper aerodigestive tract epithelium for cancer chemoprevention by polyphenols. In this paper, we summarize cancer chemopreventive attempts with emphasis on head and neck carcinogenesis and discuss some methodological issues. We present data regarding antimutagenic effects of curcumin and epigallocatechin-3-gallate in human oropharyngeal mucosa cultures exposed to cigarette smoke condensate.

  11. Epigenetic regulation by selected dietary phytochemicals in cancer chemoprevention.

    Science.gov (United States)

    Shukla, Samriddhi; Meeran, Syed M; Katiyar, Santosh K

    2014-12-01

    The growing interest in cancer epigenetics is largely due to the reversible nature of epigenetic changes which tend to alter during the course of carcinogenesis. Major epigenetic changes including DNA methylation, chromatin modifications and miRNA regulation play important roles in tumorigenic process. There are several epigenetically active synthetic molecules such as DNA methyltransferase (DNMTs) and histone deacetylases (HDACs) inhibitors, which are either approved or, are under clinical trials for the treatment of various cancers. However, most of the synthetic inhibitors have shown adverse side effects, narrow in their specificity and also expensive. Hence, bioactive phytochemicals, which are widely available with lesser toxic effects, have been tested for their role in epigenetic modulatory activities in gene regulation for cancer prevention and therapy. Encouragingly, many bioactive phytochemicals potentially altered the expression of key tumor suppressor genes, tumor promoter genes and oncogenes through modulation of DNA methylation and chromatin modification in cancer. These bioactive phytochemicals either alone or in combination with other phytochemicals showed promising results against various cancers. Here, we summarize and discuss the role of some commonly investigated phytochemicals and their epigenetic targets that are of particular interest in cancer prevention and cancer therapy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Personalizing Aspirin Use for Targeted Breast Cancer Chemoprevention in Postmenopausal Women.

    Science.gov (United States)

    Bardia, Aditya; Keenan, Tanya E; Ebbert, Jon O; Lazovich, DeAnn; Wang, Alice H; Vierkant, Robert A; Olson, Janet E; Vachon, Celine M; Limburg, Paul J; Anderson, Kristin E; Cerhan, James R

    2016-01-01

    To evaluate the association of aspirin and other nonsteroidal anti-inflammatory drugs with the incidence of postmenopausal breast cancer for risk subgroups defined by selected nonmodifiable or difficult to modify breast cancer risk factors in order to better understand the potential risk-benefit ratio for targeted chemoprevention. Postmenopausal women with no history of cancer on July 1, 1992 (N=26,580), were prospectively followed up through December 31, 2005, for breast cancer incidence (N=1581). Risk subgroups were defined on the basis of family history of breast cancer, age at menarche, age at menopause, parity/age at first live birth, personal history of benign breast disease, and body mass index. Hazard ratios (HRs) and 95% CIs adjusted for other breast cancer risk factors were estimated using Cox models. Aspirin use was associated with a lower incidence of breast cancer for women with a family history of breast cancer (HR, 0.62 for 6 or more times per week vs never use; 95% CI, 0.41-0.93) and those with a personal history of benign breast disease (HR, 0.69; 95% CI, 0.50-0.95) but not for women in higher-risk subgroups for age at menarche, age at menopause, parity/age at first live birth, or body mass index. In contrast, inverse associations with aspirin use were observed in all lower-risk subgroups. Nonsteroidal anti-inflammatory drug use had no association with breast cancer incidence. On the basis of their increased risk of breast cancer, postmenopausal women with a family history of breast cancer or a personal history of benign breast disease could potentially be targeted for aspirin chemoprevention studies. Future studies are needed to confirm these findings. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  13. Chemoprevention of colorectal cancer in individuals with previous colorectal neoplasia: systematic review and network meta-analysis.

    Science.gov (United States)

    Dulai, Parambir S; Singh, Siddharth; Marquez, Evelyn; Khera, Rohan; Prokop, Larry J; Limburg, Paul J; Gupta, Samir; Murad, Mohammad Hassan

    2016-12-05

     To assess the comparative efficacy and safety of candidate agents (low and high dose aspirin, non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs), calcium, vitamin D, folic acid, alone or in combination) for prevention of advanced metachronous neoplasia (that is, occurring at different times after resection of initial neoplasia) in individuals with previous colorectal neoplasia, through a systematic review and network meta-analysis.  Medline, Embase, Web of Science, from inception to 15 October 2015; clinical trial registries.  Randomized controlled trials in adults with previous colorectal neoplasia, treated with candidate chemoprevention agents, and compared with placebo or another candidate agent. Primary efficacy outcome was risk of advanced metachronous neoplasia; safety outcome was serious adverse events.  Two investigators identified studies and abstracted data. A Bayesian network meta-analysis was performed and relative ranking of agents was assessed with surface under the cumulative ranking (SUCRA) probabilities (ranging from 1, indicating that the treatment has a high likelihood to be best, to 0, indicating the treatment has a high likelihood to be worst). Quality of evidence was appraised with GRADE criteria.  15 randomized controlled trials (12 234 patients) comparing 10 different strategies were included. Compared with placebo, non-aspirin NSAIDs were ranked best for preventing advanced metachronous neoplasia (odds ratio 0.37, 95% credible interval 0.24 to 0.53; SUCRA=0.98; high quality evidence), followed by low-dose aspirin (0.71, 0.41 to 1.23; SUCRA=0.67; low quality evidence). Low dose aspirin, however, was ranked the safest among chemoprevention agents (0.78, 0.43 to 1.38; SUCRA=0.84), whereas non-aspirin NSAIDs (1.23, 0.95 to 1.64; SUCRA=0.26) were ranked low for safety. High dose aspirin was comparable with low dose aspirin in efficacy (1.12, 0.59 to 2.10; SUCRA=0.58) but had an inferior safety profile (SUCRA=0.51). Efficacy of

  14. Loss of BRCA1 in the Cells of Origin of Ovarian Cancer Induces Glycolysis: A Window of Opportunity for Ovarian Cancer Chemoprevention.

    Science.gov (United States)

    Chiyoda, Tatsuyuki; Hart, Peter C; Eckert, Mark A; McGregor, Stephanie M; Lastra, Ricardo R; Hamamoto, Ryuji; Nakamura, Yusuke; Yamada, S Diane; Olopade, Olufunmilayo I; Lengyel, Ernst; Romero, Iris L

    2017-04-01

    Mutations in the breast cancer susceptibility gene 1 (BRCA1) are associated with an increased risk of developing epithelial ovarian cancer. However, beyond the role of BRCA1 in DNA repair, little is known about other mechanisms by which BRCA1 impairment promotes carcinogenesis. Given that altered metabolism is now recognized as important in the initiation and progression of cancer, we asked whether the loss of BRCA1 changes metabolism in the cells of origin of ovarian cancer. The findings show that silencing BRCA1 in ovarian surface epithelial and fallopian tube cells increased glycolysis. Furthermore, when these cells were transfected with plasmids carrying deleterious BRCA1 mutations (5382insC or the P1749R), there was an increase in hexokinase-2 (HK2), a key glycolytic enzyme. This effect was mediated by MYC and the STAT3. To target the metabolic phenotype induced by loss of BRCA1, a drug-repurposing approach was used and aspirin was identified as an agent that counteracted the increase in HK2 and the increase in glycolysis induced by BRCA1 impairment. Evidence from this study indicates that the tumor suppressor functions of BRCA1 extend beyond DNA repair to include metabolic endpoints and identifies aspirin as an ovarian cancer chemopreventive agent capable of reversing the metabolic derangements caused by loss of BRCA1. Cancer Prev Res; 10(4); 255-66. ©2017 AACR. ©2016 American Association for Cancer Research.

  15. Cellular diamine levels in cancer chemoprevention: modulation by ibuprofen and membrane plasmalogens

    Directory of Open Access Journals (Sweden)

    Wood Paul L

    2011-11-01

    Full Text Available Abstract Background To develop effective strategies in cancer chemoprevention, an increased understanding of endogenous biochemical mediators that block metastatic processes is critically needed. Dietary lipids and non-steroidal anti-inflammatory drugs (NSAIDs have a published track record of providing protection against gastrointestinal malignancies. In this regard, we examined the effects of membrane plasmalogens and ibuprofen on regulation of cellular levels of diamines, polyamine mediators that are augmented in cancer cells. For these studies we utilized Chinese hamster ovary (CHO cells and NRel-4 cells, a CHO cell line with defective plasmalogen synthesis. Results NRel-4 cells, which possess cellular plasmalogen levels that are 10% of control CHO cells, demonstrated 2- to 3-fold increases in cellular diamine levels. These diamine levels were normalized by plasmalogen replacement and significantly reduced by ibuprofen. In both cases the mechanism of action appears to mainly involve increased diamine efflux via the diamine exporter. The actions of ibuprofen were not stereospecific, supporting previous studies that cyclooxygenase (COX inhibition is unlikely to be involved in the ability of NSAIDs to reduce intracellular diamine levels. Conclusions Our data demonstrate that ibuprofen, a drug known to reduce the risk of colorectal cancer, reduces cellular diamine levels via augmentation of diamine efflux. Similarly, augmentation of membrane plasmalogens can increase diamine export from control and plasmalogen-deficient cells. These data support the concept that membrane transporter function may be a therapeutic point of intervention for dietary and pharmacological approaches to cancer chemoprevention.

  16. Pharmacogenetics, pharmacogenomics and epigenetics of Nrf2-regulated xenobiotic-metabolizing enzymes and transporters by dietary phytochemical and cancer chemoprevention.

    Science.gov (United States)

    Wu, Tien-Yuan; Khor, Tin Oo; Lee, Jong Hun; Cheung, Ka Lung; Shu, Limin; Chen, Chi; Kong, Ah-Ng

    2013-07-01

    Cancer chemopreventive activities of various phytochemicals have been attributed to the modulation of xenobiotic disposition, which includes absorption, distribution, metabolism, and excretion. The interaction between xenobiotics and xenobiotic-metabolizing enzymes (XMEs) is bidirectional. XMEs are responsible for the biotransformation of xenobiotics such as bioactivation and detoxification. Conversely, xenobiotics affect XMEs through transcriptional regulation (induction or suppression) and post-translational interactions (inhibition or activation). Similar relationships also exist between xenobiotics and their transporters. Studies conducted over the past decade have demonstrated that the transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), plays a critical role in the regulation of detoxifying enzymes and transporters through a signaling system that senses and responds to redox imbalance. The role of Nrf2 in the interaction between chemopreventive phytochemicals and detoxifying enzymes/transporters has become an important topic in cancer chemoprevention. In this review, the genetic and epigenetic factors that contribute to Nrf2-mediated regulation of detoxifying XMEs and transporters are discussed in the context of cancer chemoprevention. Phytochemicals may modulate the genome as well as epigenome, altering the regulation of XMEs and transporters, which may be critical for both cancer chemoprevention and the prevention of other oxidative stress- and inflammatory-related diseases, including cardiovascular, metabolic and neurological pathologies. The pharmacogenomic expression of XMEs and transporters, with an emphasis on both genomics and epigenetics, will also be discussed.

  17. Recruitment strategies for a lung cancer chemoprevention trial involving ex-smokers.

    Science.gov (United States)

    Kye, Steve H; Tashkin, Donald P; Roth, Michael D; Adams, Bradley; Nie, Wen-Xian; Mao, Jenny T

    2009-09-01

    The ability to recruit qualified subjects who are willing to adhere to the study protocol in clinical trials is an essential component of translational research. Such tasks can be particularly challenging for chemoprevention studies when the targeted study population is healthy, at risk individuals who do not have signs or symptoms of the disease, and the study participation involves complex scheduling and invasive procedures such as bronchoscopy. In this report, we describe the recruitment process and evaluated the effectiveness of various recruitment strategies utilized in our National Cancer Institute sponsored lung cancer chemoprevention study with celecoxib. Heavy ex-smokers were recruited into the study through various methods such as radio advertisements, print media, mass mailings, flyers, internet postings and others. The number of inquiries, on-site screenees and randomization generated by each method determined the efficacy of that recruitment strategy. We prescreened 4470 individuals, invited 323 people for on-site screening and randomized 137 subjects. Radio advertisements (ads) generated the most inquiries (71.1%), followed by internet posting (11.8%), print media (6.0%), posted and racked flyers (4.4%), mass mailings (2.7%) and other strategies such as referrals from friends or family members or health care providers (2.3%). Radio ads, although costly, yielded the most subjects for on-site screening and randomization. Moreover, among the various types of radio stations, news radio stations were by far the most successful. Our results suggest that advertising on news radio is a highly effective recruitment method for successful accrual of ex-smokers into lung cancer chemoprevention trials.

  18. Cancer chemopreventive potential of apples, apple juice, and apple components.

    Science.gov (United States)

    Gerhauser, Clarissa

    2008-10-01

    Apples ( MALUS sp., Rosaceae) are a rich source of nutrient as well as non-nutrient components and contain high levels of polyphenols and other phytochemicals. Main structural classes of apple constituents include hydroxycinnamic acids, dihydrochalcones, flavonols (quercetin glycosides), catechins and oligomeric procyanidins, as well as triterpenoids in apple peel and anthocyanins in red apples. Several lines of evidence suggest that apples and apple products possess a wide range of biological activities which may contribute to health beneficial effects against cardiovascular disease, asthma and pulmonary dysfunction, diabetes, obesity, and cancer (reviewed by Boyer and Liu, Nutr J 2004). The present review will summarize the current knowledge on potential cancer preventive effects of apples, apple juice and apple extracts (jointly designated as apple products). In brief, apple extracts and components, especially oligomeric procyanidins, have been shown to influence multiple mechanisms relevant for cancer prevention in IN VITRO studies. These include antimutagenic activity, modulation of carcinogen metabolism, antioxidant activity, anti-inflammatory mechanisms, modulation of signal transduction pathways, antiproliferative and apoptosis-inducing activity, as well as novel mechanisms on epigenetic events and innate immunity. Apple products have been shown to prevent skin, mammary and colon carcinogenesis in animal models. Epidemiological observations indicate that regular consumption of one or more apples a day may reduce the risk for lung and colon cancer.

  19. Cyclooxygenase as a target for chemoprevention in colorectal cancer: lost cause or a concept coming of age?

    LENUS (Irish Health Repository)

    Doherty, Glen A

    2009-02-01

    COX-2 is upregulated at an early stage in colorectal carcinogenesis and generates prostaglandins, which promote cancer cell proliferation, impair apoptosis and enhance angiogenesis, promoting tumour growth and metastasis. There are ample data from animal models and human studies to demonstrate enhanced tumour progression associated with COX-2 activity in cancer cells. Conversely, NSAIDs including aspirin inhibit COX-2 and, therefore, have anti-neoplastic properties. There has been sustained interest in COX-2 as a chemopreventive target in colorectal cancer (CRC) and although both aspirin and COX-2 selective NSAIDs have demonstrated efficacy, adverse effects have limited their widespread adoption. In particular, evidence of the cardiovascular effects of COX-2 selective inhibitors has led to questioning of the suitability of COX-2 as a target for chemoprevention. This review examines the basis for targeting COX-2 in CRC chemoprevention, evaluates the efficacy and safety of the approach and examines future strategies in this area.

  20. Research Progress on Natural Triterpenoid Saponins in the Chemoprevention and Chemotherapy of Cancer.

    Science.gov (United States)

    Du, Jun-Rong; Long, Fang-Yi; Chen, Chu

    2014-01-01

    Triterpenoid saponins are glycosides with remarkable structural and bioactive diversity. They are becoming increasingly significant in the treatment of cancer due to their efficacy and safety. This chapter provides an update on the sources, pharmacological effects, structure-activity relationships, and clinical studies of anticancer triterpenoid saponins with a particular focus on the molecular mechanisms underlying their therapeutic properties. The correlative references and study reports described were collected through PubMed. The anticancer triterpenoid saponins enable the inhibition of cancer formation and progression by modulating multiple signaling targets related to cellular proliferation, apoptosis, autophagy, metastasis, angiogenesis, inflammation, oxidative stress, multidrug resistance, cancer stem cells, and microRNAs. This review provides new insights into the molecular basis of triterpenoid saponins in the chemoprevention and chemotherapy of cancer. © 2014 Elsevier Inc. All rights reserved.

  1. Mechanism of Selenium Chemoprevention and Therapy in Prostate Cancer

    Science.gov (United States)

    2010-11-01

    Cancer. Edited by Tindall D and Mohler J. Springer Science and Business Media and Humana Press, 2009 Abstract: 1. Lee SO, Chun JY, Nadiminty...antiproliferative effects of selenium, including antioxidant effects, enhance- ment of immune function, stimulation of apoptosis, and induction of cell...were obtained from the American Type Culture Collection (Manassas, VA) and maintained in RPMI 1640 supple- mented with 10% fetal bovine serum. The

  2. Chemoprevention of skin cancer using low HLB surfactant nanoemulsion of 5-fluorouracil: a preliminary study.

    Science.gov (United States)

    Shakeel, Faiyaz; Haq, Nazrul; Al-Dhfyan, Abdullah; Alanazi, Fars K; Alsarra, Ibrahim A

    2015-01-01

    Oral delivery of 5-fluorouracil (5-FU) is difficult due to its serious adverse effects and extremely low bioavailability. Therefore, the aim of present investigation was to develop and evaluate low HLB surfactant nanoemulsion of 5-FU for topical chemoprevention of skin cancer. Low HLB surfactant nanoemulsions were prepared by oil phase titration method. Thermodynamically stable nanoemulsions were characterized in terms of droplet size distribution, zeta potential, viscosity and refractive index. Selected formulations and control were subjected to in vitro skin permeation studies through rat skin using Franz diffusion cells. Optimized formulation F9 was subjected to stability and in vitro cytotoxic studies on melanoma cell lines. Enhancement ratio was found to be 22.33 in formulation F9 compared with control and other formulations. The values of steady state flux and permeability coefficient for formulation F9 were found to be 206.40 ± 14.56 µg cm(-2) h(-1) and 2.064 × 10(-2) ± 0.050 × 10(-2 )cm h(-1), respectively. Optimized formulation F9 was found to be physical stable. In vitro cytotoxicity studies on SK-MEL-5 cancer cells indicated that 5-FU in optimized nanoemulsion is much more efficacious than free 5-FU. From these results, it can be concluded that the developed nanoemulsion might be a promising vehicle for chemoprevention of skin cancer.

  3. Dietary Sulforaphane in Cancer Chemoprevention: The Role of Epigenetic Regulation and HDAC Inhibition.

    Science.gov (United States)

    Tortorella, Stephanie M; Royce, Simon G; Licciardi, Paul V; Karagiannis, Tom C

    2015-06-01

    Sulforaphane, produced by the hydrolytic conversion of glucoraphanin after ingestion of cruciferous vegetables, particularly broccoli and broccoli sprouts, has been extensively studied due to its apparent health-promoting properties in disease and limited toxicity in normal tissue. Recent Studies: Recent identification of a sub-population of tumor cells with stem cell-like self-renewal capacity that may be responsible for relapse, metastasis, and resistance, as a potential target of the dietary compound, may be an important aspect of sulforaphane chemoprevention. Evidence also suggests that sulforaphane may target the epigenetic alterations observed in specific cancers, reversing aberrant changes in gene transcription through mechanisms of histone deacetylase inhibition, global demethylation, and microRNA modulation. In this review, we discuss the biochemical and biological properties of sulforaphane with a particular emphasis on the anticancer properties of the dietary compound. Sulforaphane possesses the capacity to intervene in multistage carcinogenesis through the modulation and/or regulation of important cellular mechanisms. The inhibition of phase I enzymes that are responsible for the activation of pro-carcinogens, and the induction of phase II enzymes that are critical in mutagen elimination are well-characterized chemopreventive properties. Furthermore, sulforaphane mediates a number of anticancer pathways, including the activation of apoptosis, induction of cell cycle arrest, and inhibition of NFκB. Further characterization of the chemopreventive properties of sulforaphane and its capacity to be selectively toxic to malignant cells are warranted to potentially establish the clinical utility of the dietary compound as an anti-cancer compound alone, and in combination with clinically relevant therapeutic and management strategies.

  4. Optimizing Thiadiazole Analogues of Resveratrol vs. Three Chemopreventive Targets

    Science.gov (United States)

    Mayhoub, Abdelrahman S.; Marler, Laura; Kondratyuk, Tamara; Park, Eun-Jung; Pezzuto, John M.; Cushman, Mark

    2011-01-01

    Chemoprevention is an approach to decrease cancer morbidity and mortality through inhibition of carcinogenesis and prevention of disease progression. Although the trans stilbene derivative resveratrol has chemopreventive properties, its action is compromised by weak non-specific effects on many biological targets. Replacement of the stilbene ethylenic bridge of resveratrol with a 1,2,4-thiadiazole heterocycle and modification of the substituents on the two aromatic rings afforded potential chemopreventive agents with enhanced potencies and selectivities when evaluated as inhibitors of aromatase and NF-κB and inducers of quinone reductase 1 (QR1). PMID:22115839

  5. Optimizing thiadiazole analogues of resveratrol versus three chemopreventive targets.

    Science.gov (United States)

    Mayhoub, Abdelrahman S; Marler, Laura; Kondratyuk, Tamara P; Park, Eun-Jung; Pezzuto, John M; Cushman, Mark

    2012-01-01

    Chemoprevention is an approach to decrease cancer morbidity and mortality through inhibition of carcinogenesis and prevention of disease progression. Although the trans stilbene derivative resveratrol has chemopreventive properties, its action is compromised by weak non-specific effects on many biological targets. Replacement of the stilbene ethylenic bridge of resveratrol with a 1,2,4-thiadiazole heterocycle and modification of the substituents on the two aromatic rings afforded potential chemopreventive agents with enhanced potencies and selectivities when evaluated as inhibitors of aromatase and NF-κB and inducers of quinone reductase 1 (QR1). Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Chemopreventive Activity of Honokiol against 7, 12 - Dimethylbenz[a]anthracene-Induced Mammary Cancer in Female Sprague Dawley Rats

    Directory of Open Access Journals (Sweden)

    Zhenyu Wang

    2017-05-01

    Full Text Available Breast cancer is a predominant cause of death in women across the globe. Chemoprevention by using natural, dietary or synthetic products has been appearing to be a fascinating approach to combat the growing burden of breast cancer. In the current study, we intended to explore the mechanisms of chemopreventive action of honokiol against 7, 12 - dimethylbenz[a]anthracene (DMBA-induced mammary cancer in female Sprague Dawlely (SD rats. We induced mammary cancer in SD rats by administering single dose of DMBA (80 mg/kg through intra gastric route. Chemopreventive effects of honokiol (80 mg/kg, i.p. were confirmed from its ameliorating effect on the DMBA-induced anomalies such as liver marker enzymes, Phases I and II metabolizing enzymes and oxidative stress markers. Further, honokiol reversed the DMBA-induced abnormalities in inflammatory cytokines levels and serum tumor markers. Additionally, histopathological examination of mammary tissue and protein expression analysis of NF-κB revealed that honokiol is effective against DMBA-induced mammary cancer. In summary, the results of our study support the chemopreventive feature of honokiol in mammary cancer.

  7. Colorectal Cancer Chemoprevention by Mesalazine and Its Derivatives

    Directory of Open Access Journals (Sweden)

    Carmine Stolfi

    2012-01-01

    Full Text Available Patients with inflammatory bowel disease (IBD face an increased lifetime risk of developing colorectal cancer (CRC. Independent factors associated with increased risk include long disease duration, extensive colonic involvement, young age at onset of IBD, severity of inflammation, primary sclerosing cholangitis, backwash ileitis, and a family history of CRC, thus emphasising the role of intestinal inflammation as an underlying mechanism. This notion is also supported by the demonstration that the use of certain drugs used to attenuate the ongoing mucosal inflammation, such as mesalazine, seems to associate with a reduced incidence of colitis-associated CRC. In the last decade, work from many laboratories has contributed to delineate the mechanisms by which mesalazine alters CRC cell behaviour. In this paper, we review the available experimental data supporting the ability of mesalazine and its derivatives to interfere with intracellular signals involved in CRC cell growth.

  8. Chemoprevention by WR-2721

    Energy Technology Data Exchange (ETDEWEB)

    Grdina, D.J. [Argonne National Lab., IL (United States)]|[Chicago Univ., IL (United States). Dept. of Radiation and Cellular Oncology; Carnes, B.A. [Argonne National Lab., IL (United States)

    1993-05-01

    WR-2721 [S-2-(3-aminopropylamino)ethylphosphorothioic acid] is an effective chemopreventive agent. C57BL {times} BALB/c F{sub 1} female mice, were exposed to a single whole-body dose of 206 cGy from a {sup 60}Co photon source. Those groups treated with VATR-2721 (400 mg/kg) were administered the agent i.p. 30 min prior to irradiation. Over 90% of deaths were determined to be due to tumor involvement. WR-2721 afforded significant protection against life shortening due to radiation-induced tumors of connective tissue and epithelial tissue origins. Subsequent survival time in WR-2721-treated and irradiated animals as compared to matched irradiated-only controls was extended up to 59 days. A single exposure of animals to VVR-2721 did not affect the cumulative survival curves for unirradiated mice. WR-2721 possesses chemopreventive properties which can be clinically exploited to reduce the risk to therapy-induced secondary cancers in patients who otherwise would have an excellent prognosis for cure and long-term survival.

  9. Chemoprevention by WR-2721

    Energy Technology Data Exchange (ETDEWEB)

    Grdina, D.J. (Argonne National Lab., IL (United States) Chicago Univ., IL (United States). Dept. of Radiation and Cellular Oncology); Carnes, B.A. (Argonne National Lab., IL (United States))

    1993-01-01

    WR-2721 [S-2-(3-aminopropylamino)ethylphosphorothioic acid] is an effective chemopreventive agent. C57BL [times] BALB/c F[sub 1] female mice, were exposed to a single whole-body dose of 206 cGy from a [sup 60]Co photon source. Those groups treated with VATR-2721 (400 mg/kg) were administered the agent i.p. 30 min prior to irradiation. Over 90% of deaths were determined to be due to tumor involvement. WR-2721 afforded significant protection against life shortening due to radiation-induced tumors of connective tissue and epithelial tissue origins. Subsequent survival time in WR-2721-treated and irradiated animals as compared to matched irradiated-only controls was extended up to 59 days. A single exposure of animals to VVR-2721 did not affect the cumulative survival curves for unirradiated mice. WR-2721 possesses chemopreventive properties which can be clinically exploited to reduce the risk to therapy-induced secondary cancers in patients who otherwise would have an excellent prognosis for cure and long-term survival.

  10. Chemopreventive Effects of Magnesium Chloride Supplementation on Hormone Independent Prostate Cancer Cells

    Directory of Open Access Journals (Sweden)

    Elsa Quiroz

    2016-01-01

    Full Text Available Background: Lifestyle significantly impacts the risk factors associated with prostate cancer, out of which diet appears to be the most influential. An emerging chemopreventive approach, which involves the adequate intake of dietary constituents, has shown great potential in preventing the occurrence or progression of cancer. Magnesium is known to be an essential cofactor for more than 300 enzymatic processes, and is responsible for the regulation of various cellular reactions in the body. A plethora of studies have shown evidence that changes in the intracellular levels of magnesium could contribute to cell proliferation and apoptosis in some normal and malignant cells. The aim of the study was to investigate the effects of magnesium chloride (MgCl2 in DU-145 prostate cancer cells. Methodology: Cultured DU-145 cells were subjected to graded concentrations or doses (50-500 µM of MgCl2 for 48 hours. The cell viability was assessed using MTT and Resazurin reduction assays. NBT assay was also used to assess the treatment-induced intracellular ROS levels. Acridine Orange/Ethidium Bromide (AcrO/EtBr and Rh123/EtBr fluorescent stains were used to assess the cell death type and mitochondrial membrane potential (Δψm respectively. Results: The results revealed a dose-dependent decrease (P < 0.05 in cell viability in treated DU-145 cells after 48 hours. The NBT assay also revealed a dose dependent biphasic response (P < 0.05 in intracellular levels of ROS. There was a drop (P < 0.05 in ROS levels in all groups except at 100 µM, where ROS level was higher than the control. Apoptosis was the primary mode of cell death as observed in the fluorescence analysis. Conclusion: Our finding suggests that MgCl2 may be potentially chemopreventive for prostate cancer. This justifies further studies into its mechanism of action in DU-145 and other prostate cancer cell types.

  11. Glucoraphanin, the bioprecursor of the widely extolled chemopreventive agent sulforaphane found in broccoli, induces Phase-I xenobiotic metabolizing enzymes and increases free radical generation in rat liver

    Energy Technology Data Exchange (ETDEWEB)

    Perocco, Paolo [Department of Experimental Pathology, Cancerology Section, viale Filopanti 22, I-40126, University of Bologna, Bologna (Italy); Bronzetti, Giorgio [Institute of Biology and Agricultural Biotechnology - CNR Research Area, via Moruzzi, I-56124 Pisa (Italy); Canistro, Donatella; Sapone, Andrea; Affatato, Alessandra; Pozzetti, Laura; Broccoli, Massimiliano [Department of Pharmacology, Molecular Toxicology Unit, via Irnerio 48, I-40126, University of Bologna, Bologna (Italy); Valgimigli, Luca [Department of Organic Chemistry ' A. Mangini' , Viale Risorgimento 4, I-40127, Alma-Mater Studiorum, University of Bologna, Bologna (Italy); Pedulli, Gian Franco [Department of Organic Chemistry ' A. Mangini' , Viale Risorgimento 4, I-40127, Alma-Mater Studiorum, University of Bologna, Bologna (Italy); Iori, Renato [C.R.A - Research Institute for Industrial Crops, via di Corticella 133, I-40129 Bologna (Italy); Barillari, Jessica [Institute of Biology and Agricultural Biotechnology - CNR Research Area, via Moruzzi, I-56124 Pisa (Italy)]|[C.R.A - Research Institute for Industrial Crops, via di Corticella 133, I-40129 Bologna (Italy); Sblendorio, Valeriana [Department of Pharmacology, Molecular Toxicology Unit, via Irnerio 48, I-40126, University of Bologna, Bologna (Italy); Legator, Marvin S. [Department of Preventive Medicine and Community Health, Division of Environmental Toxicology, The University of Texas Medical Branch at Galveston, 700 Harborside Drive, Galveston, TX 77555-1110 (United States); Paolini, Moreno [Department of Pharmacology, Molecular Toxicology Unit, via Irnerio 48, I-40126, University of Bologna, Bologna (Italy); Abdel-Rahman, Sherif Z. [Department of Preventive Medicine and Community Health, Division of Environmental Toxicology, The University of Texas Medical Branch at Galveston, 700 Harborside Drive, Galveston, TX 77555-1110 (United States)]. E-mail: sabdelra@utmb.edu

    2006-03-20

    Epidemiological and animal studies linking high fruit and vegetable consumption to lower cancer risk have strengthened the belief that long-term administration of isolated naturally occurring dietary constituents could reduce the risk of cancer. In recent years, metabolites derived from phytoalexins, such as glucoraphanin found in broccoli and other cruciferous vegetables (Brassicaceae), have gained much attention as potential cancer chemopreventive agents. The protective effect of these micronutrients is assumed to be due to the inhibition of Phase-I carcinogen-bioactivating enzymes and/or induction of Phase-II detoxifying enzymes, an assumption that still remains uncertain. The protective effect of glucoraphanin is thought to be due to sulforaphane, an isothiocyanate metabolite produced from glucoraphanin by myrosinase. Here we show, in rat liver, that while glucoraphanin slightly induces Phase-II enzymes, it powerfully boosts Phase-I enzymes, including activators of polycyclic aromatic hydrocarbons (PAHs), nitrosamines and olefins. Induction of the cytochrome P450 (CYP) isoforms CYP1A1/2, CYP3A1/2 and CYP2E1 was confirmed by Western immunoblotting. CYP induction was paralleled by an increase in the corresponding mRNA levels. Concomitant with this Phase-I induction, we also found that glucoraphanin generated large amount of various reactive radical species, as determined by electron paramagnetic resonance (EPR) spectrometry coupled to a radical-probe technique. This suggests that long-term uncontrolled administration of glucoraphanin could actually pose a potential health hazard.

  12. Botanical Agents for the Treatment of Nonmelanoma Skin Cancer

    Directory of Open Access Journals (Sweden)

    Jillian W. Millsop

    2013-01-01

    Full Text Available Nonmelanoma skin cancers, including basal cell carcinoma and squamous cell carcinoma, are common neoplasms worldwide and are the most common cancers in the United States. Standard therapy for cutaneous neoplasms typically involves surgical removal. However, there is increasing interest in the use of topical alternatives for the prevention and treatment of nonmelanoma skin cancer, particularly superficial variants. Botanicals are compounds derived from herbs, spices, stems, roots, and other substances of plant origin and may be used in the form of dried or fresh plants, extracted plant material, or specific plant-derived chemicals. They possess multiple properties including antioxidant, anti-inflammatory, and immunomodulatory properties and are, therefore, believed to be possible chemopreventive agents or substances that may suppress or reverse the process of carcinogenesis. Here, we provide a review of botanical agents studied for the treatment and prevention of nonmelanoma skin cancers.

  13. Cancer Chemoprevention Effects of Ginger and its Active Constituents: Potential for New Drug Discovery.

    Science.gov (United States)

    Wang, Chong-Zhi; Qi, Lian-Wen; Yuan, Chun-Su

    2015-01-01

    Ginger is a commonly used spice and herbal medicine worldwide. Besides its extensive use as a condiment, ginger has been used in traditional Chinese medicine for the management of various medical conditions. In recent years, ginger has received wide attention due to its observed antiemetic and anticancer activities. This paper reviews the potential role of ginger and its active constituents in cancer chemoprevention. The phytochemistry, bioactivity, and molecular targets of ginger constituents, especially 6-shogaol, are discussed. The content of 6-shogaol is very low in fresh ginger, but significantly higher after steaming. With reported anti-cancer activities, 6-shogaol can be served as a lead compound for new drug discovery. The lead compound derivative synthesis, bioactivity evaluation, and computational docking provide a promising opportunity to identify novel anticancer compounds originating from ginger.

  14. Preclinical Cancer Chemoprevention Studies Using Animal Model of Inflammation-Associated Colorectal Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Takuji [Cytopatholgy Division, Tohkai Cytopathology Institute, Cancer Research and Prevention (TCI-CaRP), 5-1-2 Minami-uzura, Gifu 500-8285 (Japan); Department of Tumor Pathology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194 (Japan)

    2012-07-16

    Inflammation is involved in all stages of carcinogenesis. Inflammatory bowel disease, such as ulcerative colitis and Crohn’s disease is a longstanding inflammatory disease of intestine with increased risk for colorectal cancer (CRC). Several molecular events involved in chronic inflammatory process are reported to contribute to multi-step carcinogenesis of CRC in the inflamed colon. They include over-production of free radicals, reactive oxygen and nitrogen species, up-regulation of inflammatory enzymes in arachidonic acid biosynthesis pathway, up-regulation of certain cytokines, and intestinal immune system dysfunction. In this article, firstly I briefly introduce our experimental animal models where colorectal neoplasms rapidly develop in the inflamed colorectum. Secondary, data on preclinical cancer chemoprevention studies of inflammation-associated colon carcinogenesis by morin, bezafibrate, and valproic acid, using this novel inflammation-related colorectal carcinogenesis model is described.

  15. Cancer-specific chemoprevention and anti-metastatic potentials of Rheum emodi rhizome ethyl acetate extracts and identification of active principles through HPLC and GC-MS analysis.

    Science.gov (United States)

    Kumar, Devanga Ragupathi Naveen; George, Vazhapilly Cijo; Suresh, Palamadai Krishnan; Kumar, Rangasamy Ashok

    2015-01-01

    Rheum emodi Wall. ex Meissn. (Polygonaceae) is a Himalayan perennial herb which has been cultivated over 5000 years for its medicinal properties by rural and tribal people of Kashmir, and has great significance for its traditional use in Ayurvedic, Unani and folk systems of medicine for cancer treatments. However, there is lack of reports pertaining to specific-chemopreventive properties of R. emodi rhizome. The present study investigates R. emodi rhizome hot and cold ethyl acetate extracts (EHR and ECR) for specific-chemopreventive properties. The extracts were found to be effective antioxidant sources, and showed significant (P<0.05) cancer-specific cytotoxicity towards MDA-MB-231 cells (when compared to WRL-68 [non-tumoral cells]) with IC(50) values of 56.59±1.29 μg/ml (EHR) and 152.38±1.45 μg/ml (ECR) respectively, and induced apoptosis significantly (P<0.05) high in MDA-MB-231 cells (estrogen receptor-(ER)-negative) when compared to MCF-7 cells (ER-positive). Extracts also demonstrated evident anti-metastatic activity. Further, the extracts were chemically characterized through HPLC analysis which revealed major polyphenolics and the GC-MS analysis of the effective extract EHR unveiled (Methyl 6,7-dideoxy-6-C-methyl-2,3-di-O-methyl-à-D-gluco-oct-6-eno-1,5-pyranosid)urono-8,4-lactone,Chrysophanol, derivatives of cyclopropanes and a quinazoline derivative. Overall, EHR exhibited significantly better results on par with ECR, and thus could be considered for their use in designing cancer-specific chemopreventive agents against ER-negative breast cancer.

  16. The use of natural compounds for the targeting and chemoprevention of ovarian cancer.

    Science.gov (United States)

    Pistollato, Francesca; Calderón Iglesias, Ruben; Ruiz, Roberto; Aparicio, Silvia; Crespo, Jorge; Dzul Lopez, Luis; Giampieri, Francesca; Battino, Maurizio

    2017-12-28

    Among gynaecological cancers, ovarian cancer represents the leading cause of death in women. Current treatment for ovarian cancer entails surgery followed by combined chemotherapy with platinum and taxane, which are associated, particularly cisplatin, with severe side effects. While this treatment approach appears to be initially effective in a high number of patients, nearly 70% of them suffer a relapse within a few months after initial treatment. Therefore, more effective and better-tolerated treatment options are clearly needed. In recent years, several natural compounds (such as curcumin, epigallocatechin 3-gallate (EGCG), resveratrol, sulforaphane and Withaferin-A), characterized by long-term safety and negligible and/or inexistent side effects, have been proposed as possible adjuvants of traditional chemotherapy. Indeed, several in vitro and in vivo studies have shown that phytocompounds can effectively inhibit tumor cell proliferation, stimulate autophagy, induce apoptosis, and specifically target ovarian cancer stem cells (CSCs), which are generally considered to be responsible for tumor recurrence in several types of cancer. Here we review current literature on the role of natural products in ovarian cancer chemoprevention, highlighting their effects particularly on the regulation of inflammation, autophagy, proliferation and apoptosis, chemotherapy resistance, and ovarian CSC growth. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Polyphenolic Nutrients in Cancer Chemoprevention and Metastasis: Role of the Epithelial-to-Mesenchymal (EMT) Pathway.

    Science.gov (United States)

    Amawi, Haneen; Ashby, Charles R; Samuel, Temesgen; Peraman, Ramalingam; Tiwari, Amit K

    2017-08-21

    The epithelial-to-mesenchymal transition (EMT) has received significant interest as a novel target in cancer prevention, metastasis, and resistance. The conversion of cells from an epithelial, adhesive state to a mesenchymal, motile state is one of the key events in the development of cancer metastasis. Polyphenols have been reported to be efficacious in the prevention of cancer and reversing cancer progression. Recently, the antimetastatic efficacy of polyphenols has been reported, thereby expanding the potential use of these compounds beyond chemoprevention. Polyphenols may affect EMT pathways, which are involved in cancer metastasis; for example, polyphenols increase the levels of epithelial markers, but downregulate the mesenchymal markers. Polyphenols also alter the level of expression and functionality of important proteins in other signaling pathways that control cellular mesenchymal characteristics. However, the specific proteins that are directly affected by polyphenols in these signaling pathways remain to be elucidated. The aim of this review is to analyze current evidence regarding the role of polyphenols in attenuating EMT-mediated cancer progression and metastasis. We also discuss the role of the most important polyphenol subclasses and members of the polyphenols in reversing metastasis and targeting EMT. Finally, limitations and future directions to improve our understanding in this field are discussed.

  18. Potential cancer-chemopreventive activities of wine stilbenoids and flavans extracted from grape (Vitis vinifera) cell cultures.

    Science.gov (United States)

    Waffo-Téguo, P; Hawthorne, M E; Cuendet, M; Mérillon, J M; Kinghorn, A D; Pezzuto, J M; Mehta, R G

    2001-01-01

    Moderate consumption of wine is associated with a reduced risk of cancer. Grape plant cell cultures were used to purify 12 phenols: the stilbenoids trans-astringin, trans-piceid (2), trans-resveratroloside, trans-resveratrol, trans-piceatannol, cis-resveratroloside, cis-piceid, and cis-resveratrol; the flavans (+)-catechin, (-)-epicatechin, and epicatechin 3-O-gallate; and the flavan dimer procyanidin B2 3'-O-gallate. These compounds were evaluated for potential to inhibit cyclooxygenases and preneoplastic lesion formation in carcinogen-treated mouse mammary glands in organ culture. At 10 micrograms/ml, trans-astringin and trans-piceatannol inhibited development of 7,12-dimethylbenz[a]anthracene-induced preneoplastic lesions in mouse mammary glands with 68.8% and 76.9% inhibition, respectively, compared with untreated glands. The latter compound was the most potent of the 12 compounds tested in this assay, with the exception of trans-resveratrol (87.5% inhibition). In the cyclooxygenase (COX)-1 assay, trans isomers of the stilbenoids appear to be more active than cis isomers: trans-resveratrol [50% inhibitory concentration (IC50) = 14.9 microM, 96%] vs. cis-resveratrol (IC50 = 55.4 microM). In the COX-2 assay, among the compounds tested, only trans- and cis-resveratrol exhibited significant inhibitory activity (IC50 = 32.2 and 50.2 microM, respectively). This is the first report showing the potential cancer-chemopreventive activity of trans-astringin, a plant stilbenoid recently found in wine. trans-Astringin and its aglycone trans-piceatannol were active in the mouse mammary gland organ culture assay but did not exhibit activity in COX-1 and COX-2 assays. trans-Resveratrol was active in all three of the bioassays used in this investigation. These findings suggest that trans-astringin and trans-piceatannol may function as potential cancer-chemopreventive agents by a mechanism different from that of trans-resveratrol.

  19. Quimioprevenção do câncer de mama Current status of breast cancer chemoprevention

    Directory of Open Access Journals (Sweden)

    Vilmar Marques de Oliveira

    2006-12-01

    defined as the use of natural or synthetic chemical agents to reverse, suppress or prevent carcinogenic progression of invasive cancer. Drugs that act as chemoprevention agents for breast cancer are divided into two major groups: drugs that prevent Estrogen Receptor (ER - positive breast cancers [selective estrogen receptor modulators (SERM, aromatase inhibitors GnKH agonists and phytoestrogens] and drugs that prevent ER - negative breast cancers [cyclooxygenase-2 (COX-2 inhibitors, retinoids, statins, receptor tyrosine, kinase inhibitors, monoclonal antibody against HER-2 and telomerase inhibitors]. Results from the NSABP Study of Tamoxifen and Raloxifene (STAR, which compared the risk-reducing efficacy as well as toxicity of these two SERMs in a similar high-risk for breast cancer population, showed that Raloxifene is as effective as Tamoxifen in reducing the risk of non-invasive breast cancer (p=.83. It has a statistically significant lower risk of thromboembolic events and cataracts, however a non- statistically significant higher risk of noninvasive breast cancer. Based on promising data involving reduction of contralateral breast cancer risk in adjuvant studies, several aromatase inhibitors, including letrozole, anastrozole and exemestane, are being included in trials to evaluate their efficacy in breast cancer prevention in both case-control and cohort studies As such randomized studies to confirm this efficacy are needed. Positive results of several recent clinical trials for preventing breast cancer in high-risk populations suggest that chemoprevention is a rational and attractive strategy.

  20. Role of natural phenolic compounds in cancer chemoprevention via regulation of the cell cycle.

    Science.gov (United States)

    Jafari, Samineh; Saeidnia, Soodabeh; Abdollahi, Mohammad

    2014-01-01

    Natural phenolic compounds have been considered as one of the interesting secondary metabolites for their chemopreventive and chemotherapeutic effects in cancer for a long time. These are a large and diverse family of phytochemicals classified into several subgroups such as simple phenols, lignans, phenylpropanoids, flavonoids, coumarins, etc. The antioxidant potential of phenolic compounds is almost bolded in the treatment and prevention of cancer. Due to the concerns on the diverse effects of antioxidants in cancer, differentiation and clarification of their anti-neoplastic mechanisms are necessary. An important mechanism for phenolic compounds is related to their direct effect on the cell cycle progression, which has not been discussed in detail so far. This study aims to criticize the evidence on regulatory mechanisms of phenolic compounds in the cell cycle. Recent studies indicate that phenolic compounds from several subgroups significantly inhibit the proliferation of different cancer cells. The structural diversity of these compounds influences various components involved in cell cycle regulation. Forming active metabolites and sensitizing cancerous cells to chemotherapeutic medicines are additional values of these compounds. In the recent years, many studies on neoplastic cell cultures have been carried out to investigate the mechanisms of action of these compounds but dissimilarity of in vitro systems in comparison with human body in terms of metabolism and bioavailability is a major concern. Therefore, further studies are still needed.

  1. Developmental windows of breast cancer risk provide opportunities for targeted chemoprevention

    Science.gov (United States)

    Martinson, Holly A.; Lyons, Traci R.; Giles, Erin D.; Borges, Virginia F.; Schedin, Pepper

    2014-01-01

    The magnitude of the breast cancer problem implores researchers to aggressively investigate prevention strategies. However, several barriers currently reduce the feasibility of breast cancer prevention. These barriers include the inability to accurately predict future breast cancer diagnosis at the individual level, the need for improved understanding of when to implement interventions, uncertainty with respect to optimal duration of treatment, and negative side effects associated with currently approved chemoprevention therapies. None-the-less, the unique biology of the mammary gland, with its postnatal development and conditional terminal differentiation, may permit the resolution of many of these barriers. Specifically, lifecycle-specific windows of breast cancer risk have been identified that may be amenable to risk-reducing strategies. Here, we argue for prevention research focused on two of these lifecycle windows of risk: postpartum mammary gland involution and peri-menopause. We provide evidence that these windows are highly amenable to targeted, limited duration treatments. Such approaches could result in the prevention of postpartum and postmenopausal breast cancers, correspondingly. PMID:23664839

  2. Cancer chemoprevention by citrus pulp and juices containing high amounts of β-cryptoxanthin and hesperidin.

    Science.gov (United States)

    Tanaka, Takuji; Tanaka, Takahiro; Tanaka, Mayu; Kuno, Toshiya

    2012-01-01

    β-Cryptoxanthin, a carotenoid, and hesperidin, a flavonoid, possess inhibitory effects on carcinogenesis in several tissues. We recently have prepared a pulp (CHRP) and citrus juices (MJ2 and MJ5) from a satsuma mandarin (Citrus unshiu Mar.) juice (MJ). They contain high amounts of β-cryptoxanthin and hesperidin. We have demonstrated that CHRP and/or MJs inhibit chemically induced rat colon, rat tongue, and mouse lung tumorigenesis. Gavage with CHRP resulted in an increase of activities of detoxifying enzymes in the liver, colon, and tongue rats'. CHRP and MJs were also able to suppress the expression of proinflammatory cytokines and inflammatory enzymes in the target tissues. This paper describes the findings of our in vivo preclinical experiments to develop a strategy for cancer chemoprevention of colon, tongue, and lung neoplasms by use of CHRP and MJs.

  3. Biomedical properties of edible seaweed in cancer therapy and chemoprevention trials: a review.

    Science.gov (United States)

    Namvar, Farideh; Tahir, Paridah M d; Mohamad, Rosfarizan; Mahdavi, Mahnaz; Abedi, Parvin; Najafi, Tahereh Fathi; Rahmanand, Heshu Sulaiman; Jawaid, Mohammad

    2013-12-01

    This review article summarizes in vitro and in vivo experiments on seaweed anticancer activity and seaweed chemical components. Seaweed use in cancer therapy, chemopreventive randomized control trials (RCTs) and quasi-experiments are discussed. The literature reviewed in this article was obtained from various scientific sources and encompasses publications from 2000-2012. Seaweed therapeutic effects were deemed scientifically plausible and may be partially explained by the in vivo and in vitro pharmacological studies described. Although the mechanisms of action remain unclear, seaweed's anticancer properties may be attributable to its major biologically active metabolites. Much of the seaweed research outlined in this paper can serve as a foundation for explaining seaweed anticancer bioactivity. This review will open doors for developing strategies to treat malignancies using seaweed natural products.

  4. Cancer Chemoprevention by Citrus Pulp and Juices Containing High Amounts of β-Cryptoxanthin and Hesperidin

    Science.gov (United States)

    Tanaka, Takuji; Tanaka, Takahiro; Tanaka, Mayu; Kuno, Toshiya

    2012-01-01

    β-Cryptoxanthin, a carotenoid, and hesperidin, a flavonoid, possess inhibitory effects on carcinogenesis in several tissues. We recently have prepared a pulp (CHRP) and citrus juices (MJ2 and MJ5) from a satsuma mandarin (Citrus unshiu Mar.) juice (MJ). They contain high amounts of β-cryptoxanthin and hesperidin. We have demonstrated that CHRP and/or MJs inhibit chemically induced rat colon, rat tongue, and mouse lung tumorigenesis. Gavage with CHRP resulted in an increase of activities of detoxifying enzymes in the liver, colon, and tongue rats'. CHRP and MJs were also able to suppress the expression of proinflammatory cytokines and inflammatory enzymes in the target tissues. This paper describes the findings of our in vivo preclinical experiments to develop a strategy for cancer chemoprevention of colon, tongue, and lung neoplasms by use of CHRP and MJs. PMID:22174562

  5. Cancer Chemoprevention by Citrus Pulp and Juices Containing High Amounts of β-Cryptoxanthin and Hesperidin

    Directory of Open Access Journals (Sweden)

    Takuji Tanaka

    2012-01-01

    Full Text Available β-Cryptoxanthin, a carotenoid, and hesperidin, a flavonoid, possess inhibitory effects on carcinogenesis in several tissues. We recently have prepared a pulp (CHRP and citrus juices (MJ2 and MJ5 from a satsuma mandarin (Citrus unshiu Mar. juice (MJ. They contain high amounts of β-cryptoxanthin and hesperidin. We have demonstrated that CHRP and/or MJs inhibit chemically induced rat colon, rat tongue, and mouse lung tumorigenesis. Gavage with CHRP resulted in an increase of activities of detoxifying enzymes in the liver, colon, and tongue rats'. CHRP and MJs were also able to suppress the expression of proinflammatory cytokines and inflammatory enzymes in the target tissues. This paper describes the findings of our in vivo preclinical experiments to develop a strategy for cancer chemoprevention of colon, tongue, and lung neoplasms by use of CHRP and MJs.

  6. In Vivo Testing of Chemopreventive Agents Using the Dog Model of Spontaneous Prostate Carcinogenesis

    Science.gov (United States)

    2005-03-01

    low selenium status and women in two evaluable studies [16,37] (Fig. 3). was significantly increased (RR = 2.5 Netherlands; Rectal cancer risk was...cancers should an0 etldsofr 26) FIUL K, DD lead to treatments customized to certainl There were no cases of fistulas or Al,, iPes pprostate cancer, and

  7. Chemopreventive and adjuvant therapeutic potential of pomegranate (Punica granatum) for human breast cancer.

    Science.gov (United States)

    Kim, Nam Deuk; Mehta, Rajendra; Yu, Weiping; Neeman, Ishak; Livney, Talia; Amichay, Akiva; Poirier, Donald; Nicholls, Paul; Kirby, Andrew; Jiang, Wenguo; Mansel, Robert; Ramachandran, Cheppail; Rabi, Thangaiyan; Kaplan, Boris; Lansky, Ephraim

    2002-02-01

    Fresh organically grown pomegranates (Punica granatum L.) of the Wonderful cultivar were processed into three components: fermented juice, aqueous pericarp extract and cold-pressed or supercritical CO2-extracted seed oil. Exposure to additional solvents yielded polyphenol-rich fractions ('polyphenols') from each of the three components. Their actions, and of the crude whole oil and crude fermented and unfermented juice concentrate, were assessed in vitro for possible chemopreventive or adjuvant therapeutic potential in human breast cancer. The ability to effect a blockade of endogenous active estrogen biosynthesis was shown by polyphenols from fermented juice, pericarp, and oil, which inhibited aromatase activity by 60-80%. Fermented juice and pericarp polyphenols, and whole seed oil, inhibited 17-beta-hydroxysteroid dehydrogenase Type 1 from 34 to 79%, at concentrations ranging from 100 to 1,000 microg/ml according to seed oil > fermented juice polyphenols > pericarp polyphenols. In a yeast estrogen screen (YES) lyophilized fresh pomegranate juice effected a 55% inhibition of the estrogenic activity of 17-beta-estradiol; whereas the lyophilized juice by itself displayed only minimal estrogenic action. Inhibition of cell lines by fermented juice and pericarp polyphenols was according to estrogen-dependent (MCF-7) > estrogen-independent (MB-MDA-231) > normal human breast epithelial cells (MCF-10A). In both MCF-7 and MB-MDA-231 cells, fermented pomegranate juice polyphenols consistently showed about twice the anti-proliferative effect as fresh pomegranate juice polyphenols. Pomegranate seed oil effected 90% inhibition of proliferation of MCF-7 at 100 microg/ml medium, 75% inhibition of invasion of MCF-7 across a Matrigel membrane at 10 microg/ml, and 54% apoptosis in MDA-MB-435 estrogen receptor negative metastatic human breast cancer cells at 50 microg/ml. In a murine mammary gland organ culture, fermented juice polyphenols effected 47% inhibition of cancerous

  8. Azadirachta indica exhibits chemopreventive action against hepatic cancer: Studies on associated histopathological and ultrastructural changes.

    Science.gov (United States)

    Bharati, Sanjay; Rishi, Praveen; Koul, Ashwani

    2012-05-01

    The present study was designed to evaluate the anticarcinogenic potential of Azadirachta indica against N-nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis. Further, the associated histopathological and ultrastructural changes were also analyzed. Hepatic cancer model was developed by the intraperitoneal administration of NDEA to mice at weekly intervals, in successive increasing doses, for a period of 8 weeks. Aqueous A. indica leaf extract (AAILE) was administered orally at a dosage of 100 μg/g body weight thrice a week till termination of the study. A relationship between histopathological grading and chemopreventive effect of A. indica had been established at various stages of carcinogenesis. Anticancer activity of A. indica was evaluated in terms of tumor incidence, tumor multiplicity, and survival rate. A significant reduction in tumor incidence (33%), tumor multiplicity (42%), and increase in survival (34%) was observed upon administration of AAILE to NDEA-abused mice. Transmission and scanning electron microscopic investigations showed severe alterations in organelle organization, cellular arrangement, degree of differentiation, cellular metabolism, and morphology of the hepatocytes. These changes appeared to be distinctly delayed upon AAILE supplementation. The results suggest A. indica may have anticancer potential against NDEA-induced hepatic cancer. Copyright © 2011 Wiley Periodicals, Inc.

  9. Chemopreventive Effects of Oplopantriol A, a Novel Compound Isolated from Oplopanax horridus, on Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Zhiyu Zhang

    2014-07-01

    Full Text Available Oplopanax horridus is a North American botanical that has received limited investigations. We previously isolated over a dozen of the constituents from O. horridus, and among them oplopantriol A (OPT A is a novel compound. In this study, we firstly evaluated the in vivo chemoprevention activities of OPT A using the xenograft colon cancer mouse model. Our data showed that this compound significantly suppressed tumor growth with dose-related effects (p < 0.01. Next, we characterized the compound’s growth inhibitory effects in human colorectal cancer cell lines HCT-116 and SW-480. With OPT A treatment, these malignant cells were significantly inhibited in both a concentration- and time-dependent manner (both p < 0.01. The IC50 was approximately 5 µM for HCT-116 and 7 µM for SW-480 cells. OPT A significantly induced apoptosis and arrested the cell cycle at the G2/M phase. From further mechanism explorations, our data showed that OPT A significantly upregulated the expression of a cluster of genes, especially the tumor necrosis factor receptor family and caspase family, suggesting that the tumor necrosis factor-related apoptotic pathway plays a key role in OPT A induced apoptosis.

  10. Antiproliferative and chemopreventive effects of adlay seed on lung cancer in vitro and in vivo.

    Science.gov (United States)

    Chang, Hui-Chiu; Huang, Yu-Chun; Hung, Wen-Chun

    2003-06-04

    This study examined the effects of different extracts of adlay seed on the growth of human lung cancer cells in vitro and in vivo. The data showed that a methanolic extract, but not a water extract, of adlay seed exerted an antiproliferative effect on A549 lung cancer cells by inducing cell cycle arrest and apoptosis. It was also found that tumor growth in vivo was inhibited by the methanolic extract in a dose-dependent manner. The chemopreventive effect of adlay seed on the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in A/J mice was also investigated. Groups of mice were pre-fed with different diets, followed by feeding with NNK-containing drinking water for 8 months. The results indicated that feeding with diet containing 30% of powdered adlay seed reduced the number of surface lung tumors by approximately 50%. Taken together, these results indicate that the components of adlay seed exert an anticancer effect in vitro and in vivo and may be useful for the prevention of lung tumorigenesis.

  11. Evaluation of selected lichens from iceland for cancer chemopreventive and cytotoxic activity.

    Science.gov (United States)

    Ingólfsdóttir, K; Kook Lee, S; Bhat, K P; Lee, K; Chai, H B; Kristinsson, H; Song, L L; Gills, J; Gudmundsdóttir, J T; Mata-Greenwood, E; Jang, M S; Pezzuto, J M

    2000-01-01

    Cancer chemopreventive effects of organic extracts from 29 species of lichens collected in Iceland were evaluated using a panel of in vitro bioassays whereby extracts were tested for potential to induce quinone reductase (QR) and differentiation of human promyelocytic leukemia (HL-60) cells, inhibit cyclooxygenase-1 (COX-1), phorbol ester-induced ornithine decarboxylase (ODC), aromatase and sulfatase, as well as for antioxidant, estrogenic/anti-estrogenic and antiproliferative activity. In addition, the extracts were tested for cytotoxicity against 12 cancer cell lines. The most significant results were exhibited by extracts from Xanthoria elegans and Alectoria nigricans , which respectively, induced QR activity (concentration to double activity = 4.8 µg/ml) and inhibited phorbol ester-induced ODC activity with mouse 308 cells in culture (IC 50 = 2.6 µg/ml). Moderate inhibition of [ 3 H]thymidine incorporation with HL-60 cells was exhibited by the Peltigera leucophlebia extract. Several extracts prevented estrogen formation from estrogen precursors by inhibiting the enzymatic activities of aromatase ( Sphaerophorus globosus , Cetrariella delisei , Melanelia hepatizon ) and sulfatase ( Cladonia gracilis , Sphaerophorus fragilis , S. globosus ). None of the extracts demonstrated significant cytotoxic effects with selected cell lines.

  12. Fractionation of polyphenol-enriched apple juice extracts to identify constituents with cancer chemopreventive potential.

    Science.gov (United States)

    Zessner, Henriette; Pan, Lydia; Will, Frank; Klimo, Karin; Knauft, Jutta; Niewöhner, Regina; Hümmer, Wolfgang; Owen, Robert; Richling, Elke; Frank, Norbert; Schreier, Peter; Becker, Hans; Gerhauser, Clarissa

    2008-06-01

    Apples and apple juices are widely consumed and rich sources of phytochemicals. The aim of the present study was to determine which apple constituents contribute to potential chemopreventive activities, using a bioactivity-directed approach. A polyphenol-enriched apple juice extract was fractionated by various techniques. Extract and fractions were tested in a series of test systems indicative of cancer preventive potential. These test systems measured antioxidant effects, modulation of carcinogen metabolism, anti-inflammatory and antihormonal activities, and antiproliferative potential. Regression analyses indicated that 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging potential correlated with the sum of low molecular weight (LMW) antioxidants (including chlorogenic acid, flavan-3-ols, and flavonols) and procyanidins, whereas peroxyl radicals were more effectively scavenged by LMW compounds than by procyanidins. Quercetin aglycone was identified as a potent Cyp1A inhibitor, whereas phloretin and (-)-epicatechin were the most potent cyclooxygenase 1 (Cox-1) inhibitors. Aromatase and Cyp1A inhibitory potential and cytotoxicity toward HCT116 colon cancer cells increased with increasing content in procyanidins. Overall, apple juice constituents belonging to different structural classes have distinct profiles of biological activity in these in vitro test systems. Since carcinogenesis is a complex process, combination of compounds with complementary activities may lead to enhanced preventive effects.

  13. The molecular mechanism of action of aspirin, curcumin and sulforaphane combinations in the chemoprevention of pancreatic cancer.

    Science.gov (United States)

    Thakkar, Arvind; Sutaria, Dhruvitkumar; Grandhi, B Karthik; Wang, Jeffrey; Prabhu, Sunil

    2013-04-01

    Pancreatic cancer ranks as the fourth most deadly form of cancer in the United States with ~37,000 deaths each year. The present study evaluated the chemopreventive potential of a combination of aspirin (ASP), curcumin (CUR) and sulforaphane (SFN) in low doses to human pancreatic cancer cells, MIA PaCa-2 and Panc-1. Results demonstrated that low doses of ASP (1 mM), CUR (10 µM) and SFN (5 µM) (ACS) combination reduced cell viability by ~70% (Pmechanisms.

  14. 1-Alpha Hydroxyvitamin D(5) as a Chemotherapeutic and Possibly Chemopreventive Agent

    Science.gov (United States)

    2007-03-01

    report that 25-OH-D3-3-BE, a VDR-affinity alkylating derivative of the prehormone, displayed strong anti - proliferative activity in androgen-sensitive...J.J. and Gomez-Barrio,A. (2000) Setting of a colorimetric method to determine the viability of Trypanosoma cruzi epimastigotes. Parasitol Res., 86, 999...led to the hypothesis that vi- tamin D may have an anti -cancer activity . Vitamin D shows great potential as a therapy for breast cancer; however, its

  15. The chemopreventive agent myoinositol inhibits Akt and extracellular signal-regulated kinase in bronchial lesions from heavy smokers.

    Science.gov (United States)

    Han, Wei; Gills, Joell J; Memmott, Regan M; Lam, Stephen; Dennis, Phillip A

    2009-04-01

    Myoinositol is an isomer of glucose that has chemopreventive activity in animal models of cancer. In a recent phase I clinical trial, myoinositol administration correlated with a statistically significant regression of preexisting bronchial dysplastic lesions in heavy smokers. To shed light on the potential mechanisms involved, activation of Akt and extracellular signal-regulated kinase (ERK), two kinases that control cellular proliferation and survival, was assessed in 206 paired bronchial biopsies from 21 patients who participated in this clinical trial. Before myoinositol treatment, strongly positive staining for activation of Akt was detected in 27% of hyperplastic/metaplastic lesions and 58% of dysplastic lesions (P = 0.05, chi(2) test). There was also a trend toward increased activation of ERK (28% in regions of hyperplasia/metaplasia to 42% of dysplastic lesions). Following myoinositol treatment, significant decreases in Akt and ERK phosphorylation were observed in dysplastic (P 0.05). In vitro, myoinositol decreased endogenous and tobacco carcinogen-induced activation of Akt and ERK in immortalized human bronchial epithelial cells, which decreased cell proliferation and induced a G(1)-S cell cycle arrest. These results show that the phenotypic progression of premalignant bronchial lesions from smokers correlates with increased activation of Akt and ERK and that these kinases are targets of myoinositol. Moreover, they suggest that myoinositol might cause regression of bronchial dysplastic lesions through inhibition of active Akt and ERK.

  16. Infectious Agents and Cancer

    African Journals Online (AJOL)

    cancers show substantial variations in their in- cidence in different parts of the world and in particular countries, they present significant health problems. Worldwide, infections account .... cancer, oral cavity cancers. Oncorna virus - Lymphomas .... However, other risk factors including male sex, tobacco smoking and chemical.

  17. A novel combinatorial nanotechnology-based oral chemopreventive regimen demonstrates significant suppression of pancreatic cancer neoplastic lesions.

    Science.gov (United States)

    Grandhi, B Karthik; Thakkar, Arvind; Wang, Jeffrey; Prabhu, Sunil

    2013-10-01

    Pancreatic cancer is a deadly disease killing 37,000 Americans each year. Despite two decades of research on treatment options, the chances of survival are still less than 5% upon diagnosis. Recently, chemopreventive strategies have gained considerable attention as an alternative to treatment. We have previously shown significant in vitro chemopreventive effects with low-dose combinations of aspirin, curcumin, and sulforaphane (ACS) on pancreatic cancer cell lines. Here, we report the results of 24-week chemopreventive study with the oral administration of ACS combinations on the N-nitrosobis (2-oxopropyl) amine (BOP)-treated Syrian golden hamster model to suppress the progression of pancreatic intraepithelial neoplasms (PanIN) using unmodified (free drug) combinations of ACS, and nanoencapsulated (solid lipid nanoparticles; SLN) combinations of aspirin, curcumin, and free sulforaphane. The use of three different doses (low, medium, and high) of unmodified ACS combinations exhibited reduction in tumor incidence by 18%, 50%, and 68.7% respectively; whereas the modified nanoencapsulated ACS regimens reduced tumor incidence by 33%, 67%, and 75%, respectively, at 10 times lower dose compared with the free drug combinations. Similarly, although the unmodified free ACS showed a notable reduction in cell proliferation, the SLN encapsulated ACS regimens showed significant reduction in cell proliferation at 6.3%, 58.6%, and 72.8% as evidenced by proliferating cell nuclear antigen expression. Cell apoptotic indices were also upregulated by 1.5, 2.8, and 3.2 times, respectively, compared with BOP control. These studies provide a proof-of-concept for the use of an oral, low-dose, nanotechnology-based combinatorial regimen for the long-term chemoprevention of pancreatic cancer.

  18. The intriguing role of fibroblasts and c-Jun in the chemopreventive and therapeutic effect of finasteride on xenograft models of prostate cancer.

    Science.gov (United States)

    Niu, Yi-Nong; Wang, Kai; Jin, Song; Fan, Dong-Dong; Wang, Ming-Shuai; Xing, Nian-Zeng; Xia, Shu-Jie

    2016-01-01

    In a large clinical trial, finasteride reduced the rate of low-grade prostate cancer (PCa) while increasing the incidence of high-grade cancer. Whether finasteride promotes the development of high-grade tumors remains controversial. We demonstrated the role of fibroblasts and c-Jun in chemopreventive and therapeutic effect of finasteride on xenograft models of PCa. LNCaP (PC3) cells or recombinants of cancer cells and fibroblasts were implanted in male athymic nude mice treated with finasteride. Tumor growth, cell proliferation, apoptosis, p-Akt, and p-ERK1/2 were evaluated. In LNCaP (PC3) mono-grafted models, finasteride did not change the tumor growth. In recombinant-grafted models, fibroblasts and c-Jun promoted tumor growth; finasteride induced proliferation of LNCaP cells and repressed PC3 cell apoptosis. When c-Jun was knocked out, fibroblasts and/or finasteride did not promote the tumor growth. Finasteride inhibited p-Akt and p-ERK1/2 in mono-culture cancer cells while stimulating the same signaling molecules in the presence of fibroblasts. Reduced p-Akt and p-ERK1/2 were noted in the presence of c-Jun-/- fibroblasts. Fibroblasts and c-Jun promote PCa growth; finasteride further stimulates tumor growth with promoted proliferation, repressed apoptosis, and up-regulated pro-proliferative molecular pathway in the presence of fibroblasts and c-Jun. Stromal-epithelial interactions play critical roles in finasteride's therapeutic effects on PCa. Our findings have preliminary implications in using finasteride as a chemopreventive or therapeutic agent for PCa patients.

  19. The intriguing role of fibroblasts and c-Jun in the chemopreventive and therapeutic effect of finasteride on xenograft models of prostate cancer

    Directory of Open Access Journals (Sweden)

    Yi-Nong Niu

    2016-01-01

    Full Text Available In a large clinical trial, finasteride reduced the rate of low-grade prostate cancer (PCa while increasing the incidence of high-grade cancer. Whether finasteride promotes the development of high-grade tumors remains controversial. We demonstrated the role of fibroblasts and c-Jun in chemopreventive and therapeutic effect of finasteride on xenograft models of PCa. LNCaP (PC3 cells or recombinants of cancer cells and fibroblasts were implanted in male athymic nude mice treated with finasteride. Tumor growth, cell proliferation, apoptosis, p-Akt, and p-ERK1/2 were evaluated. In LNCaP (PC3 mono-grafted models, finasteride did not change the tumor growth. In recombinant-grafted models, fibroblasts and c-Jun promoted tumor growth; finasteride induced proliferation of LNCaP cells and repressed PC3 cell apoptosis. When c-Jun was knocked out, fibroblasts and/or finasteride did not promote the tumor growth. Finasteride inhibited p-Akt and p-ERK1/2 in mono-culture cancer cells while stimulating the same signaling molecules in the presence of fibroblasts. Reduced p-Akt and p-ERK1/2 were noted in the presence of c-Jun−/− fibroblasts. Fibroblasts and c-Jun promote PCa growth; finasteride further stimulates tumor growth with promoted proliferation, repressed apoptosis, and up-regulated pro-proliferative molecular pathway in the presence of fibroblasts and c-Jun. Stromal-epithelial interactions play critical roles in finasteride′s therapeutic effects on PCa. Our findings have preliminary implications in using finasteride as a chemopreventive or therapeutic agent for PCa patients.

  20. Preliminary evaluation for cancer chemopreventive and cytotoxic potential of naturally growing ethnobotanically selected plants of Pakistan.

    Science.gov (United States)

    Ihsan-ul-Haq; Mirza, Bushra; Kondratyuk, Tamara P; Park, Eun-Jung; Burns, Brittany E; Marler, Laura E; Pezzuto, John M

    2013-03-01

    Natural products are a very productive source of leads for the development of medicines. Six Pakistani plants were chosen for study based on ethnobotanical data. Exploration of important medicinal plants of Pakistan for cancer treatment. The crude extracts of the six plants and their fractions were tested for inhibition of nuclear factor κB (NFκB), aromatase, and nitric oxide (NO) production in lipopolysaccharide (LPS)-activated murine macrophage RAW 264.7 cells, induction of quinone reductase 1 (QR1), agonism of retinoid X receptor, and growth inhibition with MCF-7, LU-1 and MDA-MB-231 cancer cells. Two samples of Withania coagulans (Stocks) Dunal (Solanaceae) demonstrated inhibition of TNF-α induced activity of NFκB with IC₅₀ values of 2.6 and 4.3 µg/mL, respectively. Two fractions from W. coagulans and Euphorbia wallichii Hook F. (Euphorbiaceae) aerial parts inhibited aromatase with IC₅₀ values of 17.0 and 17.7 µg/mL, respectively. A total of 13 samples (five from E. wallichii, one from Acer oblongifolium Hort. ex Dippel (Aceraceae), one from Aster thomsonii C. B. Clarke (Asteraceae) and six from W. coagulans aerial parts with fruits) inhibited NO production with IC₅₀ values ranging from 1.3 to 15.6 µg/mL. Fourteen samples demonstrated induction of QR1 with CD ranging from 1.0 to 20.6 µg/mL, and a total of eight extracts and fractions inhibited the proliferation of cancer cells in culture with IC₅₀ values ranging from 1.2 to 7.8 µg/mL. Selected plants can be a valuable source of chemopreventive and anticancer products. W. coagulans aerial parts showed the strongest activity.

  1. Chemotherapy and Chemoprevention by Thiazolidinediones

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    Eleonore Fröhlich

    2015-01-01

    Full Text Available Thiazolidinediones (TZDs are synthetic ligands of Peroxisome-Proliferator-Activated Receptor gamma (PPARγ. Troglitazone, rosiglitazone, and pioglitazone have been approved for treatment of diabetes mellitus type II. All three compounds, together with the first TZD ciglitazone, also showed an antitumor effect in preclinical studies and a beneficial effect in some clinical trials. This review summarizes hypotheses on the role of PPARγ in tumors, on cellular targets of TZDs, antitumor effects of monotherapy and of TZDs in combination with other compounds, with a focus on their role in the treatment of differentiated thyroid carcinoma. The results of chemopreventive effects of TZDs are also considered. Existing data suggest that the action of TZDs is highly complex and that actions do not correlate with cellular PPARγ expression status. Effects are cell-, species-, and compound-specific and concentration-dependent. Data from human trials suggest the efficacy of TZDs as monotherapy in prostate cancer and glioma and as chemopreventive agent in colon, lung, and breast cancer. TZDs in combination with other therapies might increase antitumor effects in thyroid cancer, soft tissue sarcoma, and melanoma.

  2. Phytochemical Modulators of Mitochondria: The Search for Chemopreventive Agents and Supportive Therapeutics

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    Maja M. Grabacka

    2014-09-01

    Full Text Available Mitochondria are crucially important for maintaining not only the energy homeostasis, but the proper cellular functions in a general sense. Impairment of mitochondrial functions is observed in a broad variety of pathological states such as neoplastic transformations and cancer, neurodegenerative diseases, metabolic disorders and chronic inflammation. Currently, in parallel to the classical drug design approaches, there is an increasing interest in the screening for natural bioactive substances, mainly phytochemicals, in order to develop new therapeutic solutions for the mentioned pathologies. Dietary phytochemicals such as resveratrol, curcumin and sulforaphane are very well tolerated and can effectively complement classical pharmacological therapeutic regimens. In this paper we disscuss the effect of the chosen phytochemicals (e.g., resveratrol, curcumin, sulforaphane on various aspects of mitochondrial biology, namely mitochondrial biogenesis, membrane potential and reactive oxygen species production, signaling to and from the nucleus and unfolded protein response.

  3. The Role of Non-Steroidal Anti-Inflammatory Drugs in the Chemoprevention of Breast Cancer

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    Sarah L. Horn

    2010-05-01

    Full Text Available Epidemiological evidence suggests that non-steroidal anti-inflammatory drugs (NSAIDs which act as cyclooxygenase (COX-2 inhibitors may reduce breast cancer incidence by up to 20%. These agents are often taken for pain relief by older women with osteoarthritis. Age is the major risk factor for breast cancer in women with 50% cases being diagnosed in those aged >65 years. NSAIDs reduce serum estradiol by 17% in post-menopausal women and since most of these who develop breast cancers have estrogen receptor positive tumours; this suggests a possible preventative role. Careful use of these agents could provide a strategy for both relief of symptoms of osteoarthritis and also breast cancer prevention. Instead of conducting a randomised trial, proof of efficacy could be from an adequately powered cohort study within the breast screening programme.

  4. Diet phytochemicals and cutaneous carcinoma chemoprevention: A review.

    Science.gov (United States)

    Wang, Siliang; Shen, Peiliang; Zhou, Jinrong; Lu, Yin

    2017-05-01

    Cutaneous carcinoma, which has occupied a peculiar place among worldwide populations, is commonly responsible for the considerably increasing morbidity and mortality rates. Currently available medical procedures fail to completely avoid cutaneous carcinoma development or to prevent mortality. Cancer chemoprevention, as an alternative strategy, is being considered to reduce the incidence and burden of cancers through chemical agents. Derived from dietary foods, phytochemicals have become safe and reliable compounds for the chemoprevention of cutaneous carcinoma by relieving multiple pathological processes, including oxidative damage, epigenetic alteration, chronic inflammation, angiogenesis, etc. In this review, we presented comprehensive knowledges, main molecular mechanisms for the initiation and development of cutaneous carcinoma as well as effects of various diet phytochemicals on chemoprevention. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Role of 4-hydroxynonenal in chemopreventive activities of sulforaphane

    Science.gov (United States)

    Sharma, Rajendra; Sharma, Abha; Chaudhary, Pankaj; Sahu, Mukesh; Jaiswal, Shailesh; Awasthi, Sanjay; Awasthi, Yogesh C.

    2012-01-01

    Chemoprevention of cancer via herbal and dietary supplements is a logical approach to combat cancer and presently it is an attractive area of research investigations. Over the years, the use of isothiocyanates, such as sulforaphane (SFN) found in cruciferous vegetables, has been advocated as chemopreventive agents and their efficacy has been demonstrated in cell lines and animal models. In-vivo studies with SFN suggest that besides protecting normal healthy cells from environmental carcinogens it also exhibits cytotoxicity and apoptotic effects against various cancer cell types. Among several mechanisms for the chemopreventive activity of SFN against chemical carcinogenesis, its effect on drug metabolizing enzymes that causes activation/ neutralization of carcinogenic metabolites is well established. Recent studies suggest that SFN exerts its selective cytotoxicity to cancer cells via reactive oxygen species (ROS)-mediated generation of lipid peroxidation (LPO) products particularly 4-hydroxynonenal (HNE). Against the background of the known biochemical effects of SFN on normal and cancer cells, in this article we have reviewed the underlying molecular mechanisms responsible for the overall chemopreventive effects of SFN focusing on the role of HNE in these mechanisms that may also contribute to its selective cytotoxicity to cancer cells. PMID:22579574

  6. Effects of chemopreventive agents on the incidence of recurrent colorectal adenomas: a systematic review with network meta-analysis of randomized controlled trials

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    Veettil SK

    2017-05-01

    Full Text Available Sajesh K Veettil,1 Nattawat Teerawattanapong,2 Siew Mooi Ching,3,4 Kean Ghee Lim,5 Surasak Saokaew,6–9 Pochamana Phisalprapa,10 Nathorn Chaiyakunapruk7,8,11,12 1School of Pharmacy/School of Postgraduate Studies, International Medical University, Kuala Lumpur, Malaysia; 2Division of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Ubon Ratchathani University, Ubon Ratchathani, Thailand; 3Department of Family Medicine, Faculty of Medicine and Health Sciences, 4Malaysian Research Institute on Ageing, Universiti Putra Malaysia, Serdang, 5Clinical School, Department of Surgery, International Medical University, Seremban, Negeri Sembilan, 6Center of Health Outcomes Research and Therapeutic Safety (Cohorts, School of Pharmaceutical Sciences, University of Phayao, Phayao, 7School of Pharmacy, Monash University Malaysia, Selangor, Malaysia; 8Centre of Pharmaceutical Outcomes Research, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand; 9Unit of Excellence on Herbal Medicine, School of Pharmaceutical Sciences, University of Phayao, Thailand; 10Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 11School of Pharmacy, University of Wisconsin, Madison, USA; 12Health and Well-being Cluster, Global Asia Platform in the 21st Century (GA21 Platform, Monash University Malaysia, Selangor, Malaysia Background: Protective effects of several chemopreventive agents (CPAs against colorectal adenomas have been well documented in randomized controlled trials (RCTs; however, there is uncertainty regarding which agents are the most effective.Methods: We searched for RCTs published up until September 2016. Retrieved trials were evaluated using risk of bias. We performed both pairwise analysis and network meta-analysis (NMA of RCTs to compare the effects of CPAs on the recurrence of colorectal adenomas (primary outcome. Using NMA, we

  7. Anti-cancer and potential chemopreventive actions of ginseng by activating Nrf2 (NFE2L2 anti-oxidative stress/anti-inflammatory pathways

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    Wu Qing

    2010-10-01

    Full Text Available Abstract This article reviews recent basic and clinical studies of ginseng, particularly the anti-cancer effects and the potential chemopreventive actions by activating the transcriptional factor, nuclear factor (erythroid-derived 2-like 2 (Nrf2 or NFE2L2-mediated anti-oxidative stress or anti-inflammatory pathways. Nrf2 is a novel target for cancer prevention as it regulates the antioxidant responsive element (ARE, a critical regulatory element in the promoter region of genes encoding cellular phase II detoxifying and anti-oxidative stress enzymes. The studies on the chemopreventive effects of ginseng or its components/products showed that Nrf2 could also be a target for ginseng's actions. A number of papers also demonstrated the anti-inflammatory effects of ginseng. Targeting Nrf2 pathway is a novel approach to the investigation of ginseng's cancer chemopreventive actions, including some oxidative stress and inflammatory conditions responsible for the initiation, promotion and progression of carcinogenesis.

  8. Flavonoids and Other Compounds from Ouratea ferruginea (Ochnaceae as Anticancer and Chemopreventive Agents

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    Queli C. Fidelis

    2012-07-01

    Full Text Available The chemical study of the extracts from leaves and stems of Ouratea ferruginea allowed the identification of a new isoflavone, 5-hydroxy-7,3′4′5′-tetramethoxyisoflavone, and twenty two known compounds, including friedelin, 3β-friedelinol, lupeone, a mixture of sitosterol, stigmasterol and campesterol, sitosteryl- and stigmasteryl-3-O-b-D-glucopyranosides, 5,4′-dihydroxy-7,5′,3′-trimethoxyisoflavone, 5,4′-dihydroxy-7,3′-di-methoxyisoflavone (7,3′-di-O-methylorobol, 5,7,4′-trihydroxy-3′,5′-dimethoxyisoflavone (piscigenin, 2R,3R-epicatechin, syringic acid, 2,6-dimethoxybenzoquinone, 2,6-dimethoxyhydroquinone, syringic and ferulic aldehyde, a mixture of vanillic acid, 1-hydroxy-2-methoxy-4-(1E-3-hydroxy-1-propenyl-benzene and 3,5-dimethoxy-4-hydroxy-dihydrocinamaldehyde, besides amenthoflavone and 7-O-methylamenthoflavone (sequoiaflavone which are considered as chemotaxonomic markers of Ouratea. The structures were identified by IR, 1H- and 13C-NMR and GC-MS, HPLC-MS, besides comparison with literature data. The inhibitory effects of 5,4′-dihydroxy-7,5′,3′-trimethoxyisoflavone, 7,3′-di-O-methylorobol, piscigenin and 7-O-methylamenthoflavone on cytochrome P450-dependent 7-ethoxycoumarin O-deethylase (ECOD and glutathione S-transferase (GST were evaluated in vitro. The 5,4′-dihydroxy-7,5′,3′-trimethoxy-isoflavone was the best inhibitor, inhibiting almost 75% of GST activity. Sequoiaflavone was the most potent inhibitor, inhibiting ECOD assay in 75%. These activities allow us to consider both these flavonoids as potential anticancer and chemopreventive agents.

  9. Chemopreventive Activity of Vitamin E in Breast Cancer: A Focus on γ- and δ-Tocopherol

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    Nanjoo Suh

    2011-11-01

    Full Text Available Vitamin E consists of eight different variants: α-, β-, γ-, and δ-tocopherols (saturated phytyl tail and α-, β-, γ-, and δ-tocotrienols (unsaturated phytyl tail. Cancer prevention studies with vitamin E have primarily utilized the variant α-tocopherol. To no avail, a majority of these studies focused on variant α-tocopherol with inconsistent results. However, γ-tocopherol, and more recently δ-tocopherol, have shown greater ability to reduce inflammation, cell proliferation, and tumor burden. Recent results have shown that γ-enriched mixed tocopherols inhibit the development of mammary hyperplasia and tumorigenesis in animal models. In this review, we discuss the possible differences between the variant forms, molecular targets, and cancer-preventive effects of tocopherols. We recommend that a γ-enriched mixture, γ- and δ-tocopherol, but not α-tocopherol, are promising agents for breast cancer prevention and warrant further investigation.

  10. Chemopreventive activity of vitamin E in breast cancer: a focus on γ- and δ-tocopherol.

    Science.gov (United States)

    Smolarek, Amanda K; Suh, Nanjoo

    2011-11-01

    Vitamin E consists of eight different variants: α-, β-, γ-, and δ-tocopherols (saturated phytyl tail) and α-, β-, γ-, and δ-tocotrienols (unsaturated phytyl tail). Cancer prevention studies with vitamin E have primarily utilized the variant α-tocopherol. To no avail, a majority of these studies focused on variant α-tocopherol with inconsistent results. However, γ-tocopherol, and more recently δ-tocopherol, have shown greater ability to reduce inflammation, cell proliferation, and tumor burden. Recent results have shown that γ-enriched mixed tocopherols inhibit the development of mammary hyperplasia and tumorigenesis in animal models. In this review, we discuss the possible differences between the variant forms, molecular targets, and cancer-preventive effects of tocopherols. We recommend that a γ-enriched mixture, γ- and δ-tocopherol, but not α-tocopherol, are promising agents for breast cancer prevention and warrant further investigation.

  11. Chemotherapeutic prevention studies of prostate cancer

    DEFF Research Database (Denmark)

    Djavan, Bob; Zlotta, Alexandre; Schulman, Claude

    2004-01-01

    Despite advances in the detection and management of prostate cancer, this disease remains a major cause of morbidity and mortality in men. Increasing attention has focused on the role of chemoprevention for prostate cancer, ie the administration of agents that inhibit 1 or more steps in the natural...... history of prostate carcinogenesis. We review prostate cancer chemoprevention studies in Europe....

  12. Drugs with potential chemopreventive properties in relation to epithelial ovarian cancer--a nationwide case-control study.

    Science.gov (United States)

    Baandrup, Louise

    2015-07-01

    Ovarian cancer has a poor prognosis because the disease in the majority of patients is diagnosed at an advanced stage as a result of nonspecific symptoms and lack of efficient screening methods. Because of the poor prognosis of ovarian cancer and the challenge of early detection of the disease, identification of protective factors is important. It has been suggested that some commonly used drugs may have a protective effect against cancer, including ovarian cancer; however, the literature on chemopreventive measures for ovarian cancer is sparse and the results are inconclusive. Most previous studies have substantial methodological constraints, including limited study size and self-reporting of drug use, which introduces potential recall bias and misclassification. This PhD thesis includes a nationwide case-control study to evaluate associations between use of drugs with potential chemopreventive properties and risk of epithelial ovarian cancer. The study is nested in the entire Danish female population using data from the following nationwide registries: the Danish Cancer Registry, the Danish Civil Registration System, the Danish Prescription Registry, the Danish National Patient Register, and registries in Statistics Denmark on fertility, education, and income. Information from the included registries is linked by use of the unique personal identification number assigned to all Danish citizens. The cases were all women in Denmark with epithelial ovarian cancer diagnosed during 2000-2009 (Paper 1) and 2000-2011 (Papers 2 and 3), identified in the Cancer Registry. Age-matched female population controls were randomly selected from the Civil Registration System by risk-set sampling. We required that cases and controls have no history of cancer (except non-melanoma skin cancer) and that controls not previously have undergone bilateral oophorectomy or salpingo-oophorectomy. The total study population comprised 3741 epithelial ovarian cancer cases and 50,576 controls in

  13. Natural products and chemotherapeutic agents on cancer: prevention vs. treatment.

    Science.gov (United States)

    Wang, Chong-Zhi; Zhang, Zhiyu; Anderson, Samantha; Yuan, Chun-Su

    2014-01-01

    Natural products play an important role in cancer therapeutics, and lately more attentions have been paid to the prevention of major lethal malignancies, such as colorectal cancer (CRC). After oral ingestion, botanicals' parent compounds can be converted to their metabolites by the enteric microbiome, and these metabolites may have different bioactivities and variable bioavailability. In this study, we used an active ginseng metabolite, protopanaxadiol (PPD), as an example to assess its colon cancer preventive effect by comparing its effect with the treatment effect of fluorouracil (5-FU). A xenograft tumor nude mouse model with human colon cancer cell inoculation was used. After preventive PPD or treatment 5-FU administration with the same dose (30 mg/kg), tumor growth inhibition was evaluated by both a Xenogen bioluminescence imaging technique and manual tumor size measurement. Our data showed that preventive PPD very significantly inhibited the tumor growth compared to 5-FU (p cancer prevention agent. More studies are needed to explore the chemopreventive actions of PPD and its potential clinical utility.

  14. Chemoprevention gene therapy (CGT) of pancreatic cancer using perillyl alcohol and a novel chimeric serotype cancer terminator virus.

    Science.gov (United States)

    Sarkar, S; Azab, B; Quinn, B A; Shen, X; Dent, P; Klibanov, A L; Emdad, L; Das, S K; Sarkar, D; Fisher, P B

    2014-01-01

    Conditionally replication competent adenoviruses (Ads) that selectively replicate in cancer cells and simultaneously express a therapeutic cytokine, such as melanoma differentiation associated gene- 7/Interleukin-24 (mda-7/IL-24), a Cancer Terminator Virus (CTV-M7), hold potential for treating human cancers. To enhance the efficacy of the CTV-M7, we generated a chimeric Ad.5 and Ad.3 modified fiber bipartite CTV (Ad.5/3-CTV-M7) that can infect tumor cells in a Coxsackie Adenovirus receptor (CAR) independent manner, while retaining high infectivity in cancer cells containing high CAR. Although mda-7/IL-24 displays broad-spectrum anticancer properties, pancreatic ductal adenocarcinoma (PDAC) cells display an intrinsic resistance to mda-7/IL-24-mediated killing due to an mda-7/IL-24 mRNA translational block. However, using a chemoprevention gene therapy (CGT) approach with perillyl alcohol (POH) and a replication incompetent Ad to deliver mda-7/IL-24 (Ad.mda-7) there is enhanced conversion of mda-7/IL-24 mRNA into protein resulting in pancreatic cancer cell death in vitro and in vivo in nude mice containing human PDAC xenografts. This combination synergistically induces mda-7/IL-24-mediated cancer-specific apoptosis by inhibiting anti-apoptotic Bcl-xL and Bcl-2 protein expression and inducing an endoplasmic reticulum (ER) stress response through induction of BiP/GRP-78, which is most evident in chimeric-modified non-replicating Ad.5/3- mda-7- and CTV-M7-infected PDAC cells. Moreover, Ad.5/3-CTV-M7 in combination with POH sensitizes therapy-resistant MIA PaCa-2 cell lines over-expressing either Bcl-2 or Bcl-xL to mda-7/IL-24-mediated apoptosis. Ad.5/3-CTV-M7 plus POH also exerts a significant antitumor 'bystander' effect in vivo suppressing both primary and distant site tumor growth, confirming therapeutic utility of Ad.5/3-CTV-M7 plus POH in PDAC treatment, where all other current treatment strategies in clinical settings show minimal efficacy.

  15. The Role of Nutraceuticals in Chemoprevention and Chemotherapy and Their Clinical Outcomes

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    Sabita N. Saldanha

    2012-01-01

    Full Text Available The genesis of cancer is often a slow process and the risk of developing cancer increases with age. Altering a diet that includes consumption of beneficial phytochemicals can influence the balance and availability of dietary chemopreventive agents. In chemopreventive approaches, foods containing chemicals that have anticancer properties can be supplemented in diets to prevent precancerous lesions from occurring. This necessitates further understanding of how phytochemicals can potently maintain healthy cells. Fortunately there is a plethora of plant-based phytochemicals although few of them are well studied in terms of their application as cancer chemopreventive and therapeutic agents. In this analysis we will examine phytochemicals that have strong chemopreventive and therapeutic properties in vitro as well as the design and modification of these bioactive compounds for preclinical and clinical applications. The increasing potential of combinational approaches using more than one bioactive dietary compound in chemoprevention or cancer therapy will also be evaluated. Many novel approaches to cancer prevention are on the horizon, several of which are showing great promise in saving lives in a cost-effective manner.

  16. Skin Cancer Chemoprevention by Silibinin: Mechanisms and Efficacy | Division of Cancer Prevention

    Science.gov (United States)

    Project Summary Abstract Basal cell carcinoma (BCC), a non-melanoma skin cancer (NMSC) type, is a major health problem in the United States (US); annual BCC incidences alone are higher than all other cancer incidences combined (1.67 million/year). Most BCC cases are curable by surgery/radiation, but these can be painful and highly disfiguring and are not viable treatment options for BCC patients with locally advanced and metastatic disease where chemotherapy has also not proven effective. |

  17. Chemopreventive Effects of Morindia Citrifolia Juice (noni on Experimental Breast Cancer in Rats: Preliminary Study

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    Ana Milena Serrano Contreras

    2014-06-01

    Full Text Available This study determines the effect of Morindia citrifolia juice (Tahitian Noni® in the development of breast cancer induced by carcinogen agent 7.12-dimethylbenzanthracene (DMBA in rats. For this purpose, the breast cancer induction model 1.7-DMBA was used on Spraguey Dawley nulliparous rats of 35 days of age, randomly divided into three groups: group 1 control, which received no treatment, and groups 2 and 3, induced with DMBA at a dose of 55 mg/kg. The latter received a dose of noni juice of 4 ml/kg per day for 90 days. The results showed that a significant percentage (83.33% of the rats from the group induced with DMBA not treated with noni juice developed palpable breast tumors ( ≤ 2 cm of the ductal carcinoma in situ type and atypical ductal hyperplasia, compared to the other groups that did not develop any kind of tumors. In addition, it was found that rats that developed breast cancer had a lower weight gain and significantly increased water consumption (p < 0.05 compared to the other two groups. The results of the hematological and biochemical parameters showed no significant changes between groups. Histopathological changes compatible with liver toxicity were found in rats treated with noni juice. In conclusion, it was found in this preliminary study that noni juice has positive effects in modulating the development of breast cancer induced by DMBA.

  18. Chemopreventive potential of β-Sitosterol in experimental colon cancer model - an In vitro and In vivo study

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    Paulraj Gabriel M

    2010-06-01

    Full Text Available Abstract Background Asclepias curassavica Linn. is a traditional medicinal plant used by tribal people in the western ghats, India, to treat piles, gonorrhoea, roundworm infestation and abdominal tumours. We have determined the protective effect of β-sitosterol isolated from A. curassavica in colon cancer, using in vitro and in vivo models. Methods The active molecule was isolated, based upon bioassay guided fractionation, and identified as β-sitosterol on spectral evidence. The ability to induce apoptosis was determined by its in vitro antiradical activity, cytotoxic studies using human colon adenocarcinoma and normal monkey kidney cell lines, and the expression of β-catenin and proliferating cell nuclear antigen (PCNA in human colon cancer cell lines (COLO 320 DM. The chemopreventive potential of β-sitosterol in colon carcinogenesis was assessed by injecting 1,2-dimethylhydrazine (DMH, 20 mg/kg b.w. into male Wistar rats and supplementing this with β-sitosterol throughout the experimental period of 16 weeks at 5, 10, and 20 mg/kg b.w. Results β-sitosterol induced significant dose-dependent growth inhibition of COLO 320 DM cells (IC50 266.2 μM, induced apoptosis by scavenging reactive oxygen species, and suppressed the expression of β-catenin and PCNA antigens in human colon cancer cells. β-sitosterol supplementation reduced the number of aberrant crypt and crypt multiplicity in DMH-initiated rats in a dose-dependent manner with no toxic effects. Conclusion We found doses of 10-20 mg/kg b.w. β-sitosterol to be effective for future in vivo studies. β-sitosterol had chemopreventive potential by virtue of its radical quenching ability in vitro, with minimal toxicity to normal cells. It also attenuated β-catenin and PCNA expression, making it a potential anticancer drug for colon carcinogenesis.

  19. Chemopreventive potential of beta-Sitosterol in experimental colon cancer model--an in vitro and In vivo study.

    Science.gov (United States)

    Baskar, Albert A; Ignacimuthu, Savarimuthu; Paulraj, Gabriel M; Al Numair, Khalid S

    2010-06-04

    Asclepias curassavica Linn. is a traditional medicinal plant used by tribal people in the western ghats, India, to treat piles, gonorrhoea, roundworm infestation and abdominal tumours. We have determined the protective effect of beta-sitosterol isolated from A. curassavica in colon cancer, using in vitro and in vivo models. The active molecule was isolated, based upon bioassay guided fractionation, and identified as beta-sitosterol on spectral evidence. The ability to induce apoptosis was determined by its in vitro antiradical activity, cytotoxic studies using human colon adenocarcinoma and normal monkey kidney cell lines, and the expression of beta-catenin and proliferating cell nuclear antigen (PCNA) in human colon cancer cell lines (COLO 320 DM). The chemopreventive potential of beta-sitosterol in colon carcinogenesis was assessed by injecting 1,2-dimethylhydrazine (DMH, 20 mg/kg b.w.) into male Wistar rats and supplementing this with beta-sitosterol throughout the experimental period of 16 weeks at 5, 10, and 20 mg/kg b.w. beta-sitosterol induced significant dose-dependent growth inhibition of COLO 320 DM cells (IC50 266.2 microM), induced apoptosis by scavenging reactive oxygen species, and suppressed the expression of beta-catenin and PCNA antigens in human colon cancer cells. beta-sitosterol supplementation reduced the number of aberrant crypt and crypt multiplicity in DMH-initiated rats in a dose-dependent manner with no toxic effects. We found doses of 10-20 mg/kg b.w. beta-sitosterol to be effective for future in vivo studies. beta-sitosterol had chemopreventive potential by virtue of its radical quenching ability in vitro, with minimal toxicity to normal cells. It also attenuated beta-catenin and PCNA expression, making it a potential anticancer drug for colon carcinogenesis.

  20. Chemopreventive potential of β-Sitosterol in experimental colon cancer model - an In vitro and In vivo study

    Science.gov (United States)

    2010-01-01

    Background Asclepias curassavica Linn. is a traditional medicinal plant used by tribal people in the western ghats, India, to treat piles, gonorrhoea, roundworm infestation and abdominal tumours. We have determined the protective effect of β-sitosterol isolated from A. curassavica in colon cancer, using in vitro and in vivo models. Methods The active molecule was isolated, based upon bioassay guided fractionation, and identified as β-sitosterol on spectral evidence. The ability to induce apoptosis was determined by its in vitro antiradical activity, cytotoxic studies using human colon adenocarcinoma and normal monkey kidney cell lines, and the expression of β-catenin and proliferating cell nuclear antigen (PCNA) in human colon cancer cell lines (COLO 320 DM). The chemopreventive potential of β-sitosterol in colon carcinogenesis was assessed by injecting 1,2-dimethylhydrazine (DMH, 20 mg/kg b.w.) into male Wistar rats and supplementing this with β-sitosterol throughout the experimental period of 16 weeks at 5, 10, and 20 mg/kg b.w. Results β-sitosterol induced significant dose-dependent growth inhibition of COLO 320 DM cells (IC50 266.2 μM), induced apoptosis by scavenging reactive oxygen species, and suppressed the expression of β-catenin and PCNA antigens in human colon cancer cells. β-sitosterol supplementation reduced the number of aberrant crypt and crypt multiplicity in DMH-initiated rats in a dose-dependent manner with no toxic effects. Conclusion We found doses of 10-20 mg/kg b.w. β-sitosterol to be effective for future in vivo studies. β-sitosterol had chemopreventive potential by virtue of its radical quenching ability in vitro, with minimal toxicity to normal cells. It also attenuated β-catenin and PCNA expression, making it a potential anticancer drug for colon carcinogenesis. PMID:20525330

  1. Novel targets for detection of cancer and their modulation by chemopreventive natural compounds.

    Science.gov (United States)

    Ahmad, Aamir; Sakr, Wael A; Rahman, K M Wahidur

    2012-01-01

    Cancer affects the lives of millions of people. Several signaling pathways have been proposed as therapeutic targets for cancer therapy, and many more continue to be validated. With the identification and validation of therapeutic targets comes the question of designing novel strategies to effectively counter such targets. Natural compounds from dietary sources form the basis of many ancient medicinal systems. They are pleiotropic i.e. they act on multiple targets, and, therefore, are often the first agents to be tested against a novel therapeutic target. This review article summarizes the knowledge so far on some actively pursued targets - Notch, CXCR4, Wnt and sonic hedgehog (shh) pathways, the process of epithelial-mesenchymal transition (EMT) as well as molecular markers such as uPA-uPAR, survivin, FoxM1, and the microRNAs. We have performed an extensive survey of literature to list modulation of these targets by natural agents such as curcumin, indole-3-carbinol (I3C), 3,3'-diindolylmethane (DIM), resveratrol, epigallocatechin-3-gallate (EGCG), genistein etc. We believe that this review will stimulate further research for elucidating and appreciating the value of these wonderful gifts from nature.

  2. Chemopreventive Activity of MGN-3/Biobran Against Chemical Induction of Glandular Stomach Carcinogenesis in Rats and Its Apoptotic Effect in Gastric Cancer Cells.

    Science.gov (United States)

    Badr El-Din, Nariman K; Abdel Fattah, Salma M; Pan, Deyu; Tolentino, Lucilene; Ghoneum, Mamdooh

    2016-12-01

    In the current study, we investigated the chemopreventive activity of arabinoxylan rice bran, MGN-3/Biobran, against chemical induction of glandular stomach carcinogenesis in rats. Gastric cancer was induced by carcinogen methylnitronitrosoguanidine (MNNG), and rats received MNNG alone or MNNG plus Biobran (40 mg/kg body weight) for a total of 8 months. Averaged results from 2 separate readings showed that exposure to MNNG plus Biobran caused gastric dysplasia and cancer (adenocarcinoma) in 4.5/12 rats (9/24 readings, 37.5%), with 3.5/12 rats (7/24 readings, 29.2%) showing dysplasia and 1/12 rats (8.3%) developing adenocarcinoma. In contrast, in rats treated with MNNG alone, 8/10 (80%) developed dysplasia and adenocarcinoma, with 6/10 rats (60%) showing dysplasia and 2/10 rats (20%) developing adenocarcinoma. The effect of combining both agents was also associated with significant suppression of the expression of the tumor marker Ki-67 and remarkable induction in the apoptotic gastric cancer cells via mitochondrial-dependent pathway as indicated by the upregulation in p53 expression, Bax expression, downregulation in Bcl-2 expression, an increase in Bax/Bcl-2 ratio, and an activation of caspase-3. In addition, Biobran treatment induced cell-cycle arrest in the subG1 phase, where the hypodiploid cell population was markedly increased. Moreover, Biobran treatment protected rats against MNNG-induced significant decrease in lymphocyte levels. We conclude that Biobran provides protection against chemical induction of glandular stomach carcinogenesis in rats and may be useful for the treatment of human patients with gastric cancer. © The Author(s) 2016.

  3. Bioactive natural products for chemoprevention and treatment of castration-resistant prostate cancer.

    Science.gov (United States)

    Kallifatidis, Georgios; Hoy, James J; Lokeshwar, Bal L

    2016-10-01

    Prostate cancer (PCa), a hormonally-driven cancer, ranks first in incidence and second in cancer related mortality in men in most Western industrialized countries. Androgen and androgen receptor (AR) are the dominant modulators of PCa growth. Over the last two decades multiple advancements in screening, treatment, surveillance and palliative care of PCa have significantly increased quality of life and survival following diagnosis. However, over 20% of patients initially diagnosed with PCa still develop an aggressive and treatment-refractory disease. Prevention or treatment for hormone-refractory PCa using bioactive compounds from marine sponges, mushrooms, and edible plants either as single agents or as adjuvants to existing therapy, has not been clinically successful. Major advancements have been made in the identification, testing and modification of the existing molecular structures of natural products. Additionally, conjugation of these compounds to novel matrices has enhanced their bio-availability; a big step towards bringing natural products to clinical trials. Natural products derived from edible plants (nutraceuticals), and common folk-medicines might offer advantages over synthetic compounds due to their broader range of targets, as compared to mostly single target synthetic anticancer compounds; e.g. kinase inhibitors. The use of synthetic inhibitors or antibodies that target a single aberrant molecule in cancer cells might be in part responsible for emergence of treatment refractory cancers. Nutraceuticals that target AR signaling (epigallocatechin gallate [EGCG], curcumin, and 5α-reductase inhibitors), AR synthesis (ericifolin, capsaicin and others) or AR degradation (betulinic acid, di-indolyl diamine, sulphoraphane, silibinin and others) are prime candidates for use as adjuvant or mono-therapies. Nutraceuticals target multiple pathophysiological mechanisms involved during cancer development and progression and thus have potential to simultaneously

  4. Chemopreventive efficacy of curcumin-loaded PLGA microparticles in a transgenic mouse model of HER-2-positive breast cancer.

    Science.gov (United States)

    Grill, Alex E; Shahani, Komal; Koniar, Brenda; Panyam, Jayanth

    2017-04-17

    Curcumin has shown promising inhibitory activity against HER-2-positive tumor cells in vitro but suffers from poor oral bioavailability in vivo. Our lab has previously developed a polymeric microparticle formulation for sustained delivery of curcumin for chemoprevention. The goal of this study was to examine the anticancer efficacy of curcumin-loaded polymeric microparticles in a transgenic mouse model of HER-2 cancer, Balb-neuT. Microparticles were injected monthly, and mice were examined for tumor appearance and growth. Initiating curcumin microparticle treatment at 2 or 4 weeks of age delayed tumor appearance by 2-3 weeks compared to that in control mice that received empty microparticles. At 12 weeks, abnormal (lobular hyperplasia, carcinoma in situ, and invasive carcinoma) mammary tissue area was significantly decreased in curcumin microparticle-treated mice, as was CD-31 staining. Curcumin treatment decreased mammary VEGF levels significantly, which likely contributed to slower tumor formation. When compared to saline controls, however, blank microparticles accelerated tumorigenesis and curcumin treatment abrogated this effect, suggesting that PLGA microparticles enhance tumorigenesis in this model. PLGA microparticle administration was shown to be associated with higher plasma lactic acid levels and increased activation of NF-κΒ. The unexpected side effects of PLGA microparticles may be related to the high dose of the microparticles that was needed to achieve sustained curcumin levels in vivo. Approaches that can decrease the overall dose of curcumin (for example, by increasing its potency or reducing its clearance rate) may allow the development of sustained release curcumin dosage forms as a practical approach to cancer chemoprevention.

  5. Chemopreventive properties of curcumin analogues ...

    African Journals Online (AJOL)

    Purpose: To examine the chemopreventive activity of curcumin analogues, hexagamavunone-0 (HGV-. 0) and gamavutone-0 (GVT-0), compared to curcumin in a colorectal cancer model in Wistar rats. Methods: Rats (n = 25) were assigned to one of five groups (n = 5 in each group). Colorectal cancer was induced in the ...

  6. Cancer Chemopreventive Effects of Boswellia sacra Gum Resin Hydrodistillates on Invasive Urothelial Cell Carcinoma: Report of a Case.

    Science.gov (United States)

    Xia, Ding; Lou, Weiwei; Fung, Kar-Ming; Wolley, Cole L; Suhail, Mahmoud M; Lin, Hsueh-Kung

    2017-12-01

    A 52-year-old Hispanic male presented with hematuria and was later diagnosed with a large invasive high-grade urothelial cell carcinoma (UCC) of the urinary bladder, but with ambiguous pT1/pT2 staging regarding musclaris propria invasion by UCC. The conventional treatment including radical cystoprostatectomy followed by neoadjuvant chemotherapy with or without radiation therapy was presented. The patient decided to delay the standard therapy until a later stage, but elected to go through transurethral resection of bladder tumor (TURBT) without Bacillus Calmette-Guérin instillation. Following TURBT, the patient started oral Boswellia sacra gum resin (aka frankincense or Ru Xiang in Chinese) hydrodistillates (BSGRH) administration at 3 mL daily with lifestyle changes, and continued this regimen in the last 25 months. Within the first year after diagnosis, the patient experienced 2 recurrences. Recurrent tumors were removed by TURBT alone and both tumors were far smaller than the original one. After the second recurrence, the patient has no detectible cancer in the bladder based on cystoscopy for 14 months and has an intact genitourinary system. His liver and kidney functions are considered to be normal based on blood chemistry tests. This index case suggests that BSGRH may have cancer chemopreventive effects on UCC. The use of Boswellia-derived products in the management of cancer has been well document in other published studies, and boswellic acids have been suggested to be the major component. However, BSGRH contains very little boswellic acids. Demonstration of cancer chemoprevention using BSGRH is one step forward in isolating the key components other than boswellic acids in frankincense. The critical question as to whether these components can simultaneously activate multiple pathways in cancer cells to execute cancer suppression/cytotoxicity or prevention effects remains to be addressed. More studies including identification of key molecules, pharmacokinetics

  7. Chemopreventive effects of synthetic C-substituted diindolylmethanes originating from cruciferous vegetables in human oral cancer cells.

    Science.gov (United States)

    Shin, Ji-Ae; Shim, Jung-Hyun; Choi, Eun-Sun; Leem, Dae-Ho; Kwon, Ki Han; Lee, Syng-Ook; Safe, Stephen; Cho, Nam-Pyo; Cho, Sung-Dae

    2011-09-01

    Diindolylmethane (DIM), an isothiocyanate found in cruciferous vegetables, has been shown to have cancer chemopreventive effects. A series of synthetic C-substituted DIMs (C-DIMs) analogs was developed, including DIM-C-pPhtBu and DIM-C-pPhC6H5, which exhibited better inhibitory activity in cancer cells than DIM. This study examined the effects of C-DIMs on the growth of human oral cancer cells. DIM-C-pPhtBu and DIM-C-pPhC6H5 decreased the number of viable KB cells and induced caspase-dependent apoptosis. The apoptotic cell death was accompanied by a change in Bax/Bcl-2 ratio and damage to mitochondrial membrane potential through the induction of death receptor 5 and the cleavage of Bid and caspase 8. Studies on the mechanism of action showed that the apoptotic cell death induced by DIM-C-pPhtBu and DIM-C-pPhC6H5 was mediated by endoplasmic reticulum stress. In addition, C-DIMs inhibited cell proliferation and induced PARP cleavage through death receptor 5 and CHOP in HEp-2 and HN22 cells. This provides the first evidence that synthetic C-DIMs originating from cruciferous vegetables induce apoptosis in human oral cancer cells through the endoplasmic reticulum stress pathway.

  8. Frugal chemoprevention: targeting Nrf2 with foods rich in sulforaphane.

    Science.gov (United States)

    Yang, Li; Palliyaguru, Dushani L; Kensler, Thomas W

    2016-02-01

    With the properties of efficacy, safety, tolerability, practicability and low cost, foods containing bioactive phytochemicals are gaining significant attention as elements of chemoprevention strategies against cancer. Sulforaphane [1-isothiocyanato-4-(methylsulfinyl)butane], a naturally occurring isothiocyanate produced by cruciferous vegetables such as broccoli, is found to be a highly promising chemoprevention agent against not only a variety of cancers such as breast, prostate, colon, skin, lung, stomach or bladder, but also cardiovascular disease, neurodegenerative diseases, and diabetes. For reasons of experimental exigency, preclinical studies have focused principally on sulforaphane itself, while clinical studies have relied on broccoli sprout preparations rich in either sulforaphane or its biogenic precursor, glucoraphanin. Substantive subsequent evaluation of sulforaphane pharmacokinetics and pharmacodynamics has been undertaken using either pure compound or food matrices. Sulforaphane affects multiple targets in cells. One key molecular mechanism of action for sulforaphane entails activation of the Nrf2-Keap1 signaling pathway although other actions contribute to the broad spectrum of efficacy in different animal models. This review summarizes the current status of pre-clinical chemoprevention studies with sulforaphane and highlights the progress and challenges for the application of foods rich in sulforaphane and/or glucoraphanin in the arena of clinical chemoprevention. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Targeting COX-2 expression by natural compounds: a promising alternative strategy to synthetic COX-2 inhibitors for cancer chemoprevention and therapy.

    Science.gov (United States)

    Cerella, Claudia; Sobolewski, Cyril; Dicato, Mario; Diederich, Marc

    2010-12-15

    Cyclooxygenase (COX)-2 is a pro-inflammatory immediate early response protein, chronically up-regulated in many pathological conditions. In autoimmune diseases, it is responsible for degenerative effects whereas in cancer, it correlates with poor prognosis. A constitutive expression of COX-2 is triggered since the earliest steps of carcinogenesis. Consequently, strategies aimed at inhibiting COX-2 enzymatic activity have been clinically applied for the treatment of autoimmune disorders; in addition, the same approaches are currently investigated for anti-cancer purposes. However, COX-2 protein inhibitors (i.e., NSAIDs and COXIBs) are not amenable to prolonged administration since they may cause severe side effects, and efforts are underway to identify alternative approaches for chemoprevention/therapy. COX-2 expression is a multi-step process, highly regulated at transcriptional and post-transcriptional levels. Defects in the modulation of one or both of these steps may be found in pathological conditions. Targeting COX-2 expression may therefore represent a promising strategy, by which the same preventive and therapeutic benefits may be gained while avoiding the severe side effects of COX-2 enzymatic inhibition. Naturally occurring compounds derived from plants/organisms represent a huge source of biologically active molecules, that remains largely unexplored. Derived from plants/organisms used in traditional forms of medicine or as dietary supplements, these compounds have been experimentally investigated for their anti-inflammatory and anti-cancer potential. In this review, we will analyze how natural compounds may modulate the multistep regulation of COX-2 gene expression and discuss their potential as a new generation of COX-2 targeting agents alternative to the synthetic COX-2 inhibitors. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. Targeting angiogenic pathway for chemoprevention of experimental colon cancer using C-phycocyanin as cyclooxygenase-2 inhibitor.

    Science.gov (United States)

    Saini, Manpreet Kaur; Sanyal, Sankar Nath

    2014-06-01

    An angiogenic pathway was studied that involved stromal tissue degradation with matrix metalloproteinases (MMPs), vesicular endothelial growth factor-A (VEGF-A), and hypoxia inducible factor-1α (HIF-1α) mediated growth regulation in a complex interaction with chemokines, such as monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1β (MIP-1β). Gene and protein expression was studied with real-time PCR, Western immunoblot, and immunofluorescence. Morphological and histopathological analysis of tumor was done, as also the activity of MMPs and HIF-1α by gelatin zymography and ELISA. Binding interactions of proteins were studied by molecular docking. Piroxicam, a traditional NSAID and C-phycocyanin, a biliprotein from Spirulina platensis, were utilized in the chemoprevention of DMH-induced rat colon cancer. A significant number of tumors was evident in DMH treated animals, while with piroxicam and C-phycocyanin, the number and size of tumors/lesions were reduced. Colonic tissues showed severe dysplasia, tubular adenoma, and adenocarcinoma from DMH, with invasive features along with signet ring cell carcinoma. No occurrence of carcinoma was detected in either of the drug treatments or in a combination regimen. An elevated VEGF-A, MMP-2, and MMP-9 level was observed, which is required for metastasis and invasion into surrounding tissues. Drugs induced chemoprevention by down-regulating these proteins. Piroxicam docked in VEGF-A binding site of VEGF-A receptors i.e., VEGFR1 and VEGFR2, while phycocyanobilin (a chromophore of C-phycocyanin) docked with VEGFR1 alone. HIF-1α is up-regulated which is associated with increased oxygen demand and angiogenesis. MCP-1 and MIP-1β expression was also found altered in DMH and regulated by the drugs. Anti-angiogenic role of piroxicam and C-phycocyanin is well demonstrated.

  11. Growth-inhibitory effects of the chemopreventive agent indole-3-carbinol are increased in combination with the polyamine putrescine in the SW480 colon tumour cell line

    Directory of Open Access Journals (Sweden)

    Gescher Andreas

    2003-01-01

    Full Text Available Abstract Background Many tumours undergo disregulation of polyamine homeostasis and upregulation of ornithine decarboxylase (ODC activity, which can promote carcinogenesis. In animal models of colon carcinogenesis, inhibition of ODC activity by difluoromethylornithine (DFMO has been shown to reduce the number and size of colon adenomas and carcinomas. Indole-3-carbinol (I3C has shown promising chemopreventive activity against a range of human tumour cell types, but little is known about the effect of this agent on colon cell lines. Here, we investigated whether inhibition of ODC by I3C could contribute to a chemopreventive effect in colon cell lines. Methods Cell cycle progression and induction of apoptosis were assessed by flow cytometry. Ornithine decarboxylase activity was determined by liberation of CO2 from 14C-labelled substrate, and polyamine levels were measured by HPLC. Results I3C inhibited proliferation of the human colon tumour cell lines HT29 and SW480, and of the normal tissue-derived HCEC line, and at higher concentrations induced apoptosis in SW480 cells. The agent also caused a decrease in ODC activity in a dose-dependent manner. While administration of exogenous putrescine reversed the growth-inhibitory effect of DFMO, it did not reverse the growth-inhibition following an I3C treatment, and in the case of the SW480 cell line, the effect was actually enhanced. In this cell line, combination treatment caused a slight increase in the proportion of cells in the G2/M phase of the cell cycle, and increased the proportion of cells undergoing necrosis, but did not predispose cells to apoptosis. Indole-3-carbinol also caused an increase in intracellular spermine levels, which was not modulated by putrescine co-administration. Conclusion While indole-3-carbinol decreased ornithine decarboxylase activity in the colon cell lines, it appears unlikely that this constitutes a major mechanism by which the agent exerts its antiproliferative

  12. Growth-inhibitory effects of the chemopreventive agent indole-3-carbinol are increased in combination with the polyamine putrescine in the SW480 colon tumour cell line

    Science.gov (United States)

    Hudson, E Ann; Howells, Lynne M; Gallacher-Horley, Barbara; Fox, Louise H; Gescher, Andreas; Manson, Margaret M

    2003-01-01

    Background Many tumours undergo disregulation of polyamine homeostasis and upregulation of ornithine decarboxylase (ODC) activity, which can promote carcinogenesis. In animal models of colon carcinogenesis, inhibition of ODC activity by difluoromethylornithine (DFMO) has been shown to reduce the number and size of colon adenomas and carcinomas. Indole-3-carbinol (I3C) has shown promising chemopreventive activity against a range of human tumour cell types, but little is known about the effect of this agent on colon cell lines. Here, we investigated whether inhibition of ODC by I3C could contribute to a chemopreventive effect in colon cell lines. Methods Cell cycle progression and induction of apoptosis were assessed by flow cytometry. Ornithine decarboxylase activity was determined by liberation of CO2 from 14C-labelled substrate, and polyamine levels were measured by HPLC. Results I3C inhibited proliferation of the human colon tumour cell lines HT29 and SW480, and of the normal tissue-derived HCEC line, and at higher concentrations induced apoptosis in SW480 cells. The agent also caused a decrease in ODC activity in a dose-dependent manner. While administration of exogenous putrescine reversed the growth-inhibitory effect of DFMO, it did not reverse the growth-inhibition following an I3C treatment, and in the case of the SW480 cell line, the effect was actually enhanced. In this cell line, combination treatment caused a slight increase in the proportion of cells in the G2/M phase of the cell cycle, and increased the proportion of cells undergoing necrosis, but did not predispose cells to apoptosis. Indole-3-carbinol also caused an increase in intracellular spermine levels, which was not modulated by putrescine co-administration. Conclusion While indole-3-carbinol decreased ornithine decarboxylase activity in the colon cell lines, it appears unlikely that this constitutes a major mechanism by which the agent exerts its antiproliferative effect, although accumulation

  13. Development of an Inflammation-Associated Colorectal Cancer Model and Its Application for Research on Carcinogenesis and Chemoprevention

    Directory of Open Access Journals (Sweden)

    Takuji Tanaka

    2012-01-01

    Full Text Available Chronic inflammation is a well-recognized risk factor for development of human cancer in several tissues, including large bowel. Inflammatory bowel disease, including ulcerative colitis and Crohn’s disease, is a longstanding inflammatory disease of intestine with increased risk for colorectal cancer development. Several molecular events involved in chronic inflammatory process may contribute to multistep carcinogenesis of human colorectal cancer in the inflamed colon. They include overproduction of reactive oxygen and nitrogen species, overproduction and upregulation of productions and enzymes of arachidonic acid biosynthesis pathway and cytokines, and intestinal immune system dysfunction. In this paper, I will describe several methods to induce colorectal neoplasm in the inflamed colon. First, I will introduce a protocol of a novel inflammation-associated colon carcinogenesis in mice. In addition, powerful tumor-promotion/progression activity of dextran sodium sulfate in the large bowel of ApcMin/+ mice will be described. Finally, chemoprevention of inflammation-associated colon carcinogenesis will be mentioned.

  14. Synergistic chemopreventive effects of nobiletin and atorvastatin on colon carcinogenesis.

    Science.gov (United States)

    Wu, Xian; Song, Mingyue; Qiu, Peiju; Rakariyatham, Kanyasiri; Li, Fang; Gao, Zili; Cai, Xiaokun; Wang, Minqi; Xu, Fei; Zheng, Jinkai; Xiao, Hang

    2017-04-01

    Different cancer chemopreventive agents may act synergistically and their combination may produce enhanced protective effects against carcinogenesis than each individual agent alone. Herein, we investigated the chemopreventive effects of nobiletin (NBT, a citrus polymethoxyflavone) and atorvastatin (ATST, a lipid-lowering drug) in colon cancer cells/macrophages and an azoxymethane (AOM)-induced colon carcinogenesis rat model. The results demonstrated that co-treatments of NBT/ATST produced enhanced growth inhibitory and anti-inflammatory effects on the colon cancer cells and macrophages, respectively. Isobologram analysis confirmed that these interactions between NBT and ATST were synergistic. NBT/ATST co-treatment also synergistically induced extensive cell cycle arrest and apoptosis in colon cancer cells. Oral administration of NBT (0.1%, w/w in diet) or ATST (0.04%, w/w in diet) significantly decreased colonic tumor incidence and multiplicity in AOM-treated rats. Most importantly, co-treatment of NBT/ATST at their half doses (0.05% NBT + 0.02% ATST, w/w in diet) resulted in even stronger inhibitory effects on colonic tumor incidence and multiplicity than did NBT or ATST alone at higher doses. Statistical analysis confirmed that the enhanced chemopreventive activities against colon carcinogenesis in rats by the NBT/ATST combination were highly synergistic. Our results further demonstrated that NBT/ATST co-treatment profoundly modulated key cellular signaling regulators associated with inflammation, cell proliferation, cell cycle progression, apoptosis, angiogenesis and metastasis in the colon of AOM-treated rats. In conclusion, for the first time, our results demonstrated a strong synergy in inhibiting colon carcinogenesis produced by the co-treatment of NBT and ATST, which provided a scientific basis for using NBT in combination with ATST for colon cancer chemoprevention in humans. © The Author 2017. Published by Oxford University Press. All rights reserved

  15. Linking genomic responses of gonads with reproductive impairment in marine medaka (Oryzias melastigma) exposed chronically to the chemopreventive and antifouling agent, 3,3′-diindolylmethane (DIM)

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Lianguo [Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong SAR (China); Au, Doris W.T. [State Key Laboratory in Marine Pollution, Department of Biology and Chemistry, City University of Hong Kong, Kowloon, Hong Kong SAR (China); Hu, Chenyan [School of Chemistry and Environmental Engineering, Wuhan Institute of Technology, Wuhan 430072 (China); Zhang, Weipeng [Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong SAR (China); Zhou, Bingsheng [State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China); Cai, Lin [Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong SAR (China); Giesy, John P. [Department of Veterinary Biomedical Sciences and Toxicology Centre, University of Saskatchewan, 44 Campus Drive, Saskatoon, SK S7N 5B3 (Canada); Department of Zoology, and Center for Integrative Toxicology, Michigan State University, East Lansing, MI (United States); Qian, Pei-Yuan, E-mail: boqianpy@ust.hk [Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong SAR (China)

    2017-02-15

    combination with chemical stability and potent endocrine disruption, the results of this study can inform decisions about the use of DIM either as chemopreventive or antifouling agent.

  16. The role of chemoprevention in cancer control El papel de la quimioprevención en el control del cáncer

    Directory of Open Access Journals (Sweden)

    EVA BUIATTI

    1997-07-01

    Full Text Available Chemoprevention can be defined as the use of chemical compounds or medicines to prevent the occurrence of precancerous lesions (markers or to slow down or revert the progression of clinically established disease. The use of randomized trial design is considered the gold standard for evaluating the preventive value of chemicals against cancer, since they control for confounding and avoid information bias. The principal school in relation to cancer control through chemoprevention is based on studies of cancer and diet. Initially, ecological studies set the cornerstone, but later case-control studies supported the hypothesis of an inverse association between foods and cancer risk (principally epithelial, suggesting that determined micronutrients participate as protection in this process. Other studies include specific chemical analyses, which have potential problems that could lead to erroneous conclusions, such as sample and measurement errors. During this decade randomized intervention trials have been carried out to test this hypothesis, but conclusions have been so diverse and the designs used have been so different in terms of levels of exposure, that consistent conclusions are not possible. We can conclude that using studies with randomized, double-blind, controlled designs is interesting, but problems remain to be solved, including: agent selection, the design to be chosen, and especially the balance between benefits sought and secondary effects, including cost-effectiveness, since some chemicals cannot compete with other preventive or therapeutic measures.La quimioprevención puede definirse como el uso de medicamentos o compuestos químicos, que se utilizan para prevenir la ocurrencia de lesiones precancerosas (marcadores, o bien para retardar o revertir la progresión de padecimientos clínicamente establecidos. La utilización de diseños de ensayos aleatorizados, se considera el estándar de oro para evaluar el valor preventivo de los

  17. An Improved Synthesis of 7, 8-Epoxy-1,3,11-cembratriene-15R(α, 16-diol, a Cembranoid of Marine Origin with a Potent Cancer Chemopreventive Activity

    Directory of Open Access Journals (Sweden)

    Sherief I. Khalifa

    2004-02-01

    Full Text Available An effective method for the synthesis of 7,8-epoxy-1,3,11-cembratriene-15R(α, 16-diol and its in vitro Epstein-Barr Virus Early Antigen (EBV-EA Activation Chemopreventive Assay are reported. This semisynthetic product is a new cembranoid with a potent tumor inhibitory activity that is expected to be a lead compound for a new class of chemopreventive agents of marine origin.

  18. Moringa oleifera Lam: Targeting Chemoprevention.

    Science.gov (United States)

    Karim, Nurul Ashikin Abd; Ibrahim, Muhammad Din; Kntayya, Saie Brindha; Rukayadi, Yaya; Hamid, Hazrulizawati Abd; Razis, Ahmad Faizal Abdull

    2016-01-01

    Moringa oleifera Lam, family Moringaceae, is a perennial plant which is called various names, but is locally known in Malaysia as "murungai" or "kelor". Glucomoringin, a glucosinolate with from M. oleifera is a major secondary metabolite compound. The seeds and leaves of the plant are reported to have the highest amount of glucosinolates. M. oleifera is well known for its many uses health and benefits. It is claimed to have nutritional, medicinal and chemopreventive potentials. Chemopreventive effects of M. oleifera are expected due to the existence of glucosinolate which it is reported to have the ability to induce apoptosis in anticancer studies. Furthermore, chemopreventive value of M. oleifera has been demonstrated in studies utilizing its leaf extract to inhibit the growth of human cancer cell lines. This review highlights the advantages of M. oleifera targeting chemoprevention where glucosinolates could help to slow the process of carcinogenesis through several molecular targets. It is also includes inhibition of carcinogen activation and induction of carcinogen detoxification, anti-inflammatory, anti-tumor cell proliferation, induction of apoptosis and inhibition of tumor angiogenesis. Finally, for synergistic effects of M. oleifera with other drugs and safety, essential for chemoprevention, it is important that it safe to be consumed by human body and works well. Although there is promising evidence about M. oleifera in chemoprevention, extensive research needs to be done due to the expected rise of cancer in coming years and to gain more information about the mechanisms involved in M. oleifera influence, which could be a good source to inhibit several major mechanisms involved in cancer development.

  19. Estrogen- and stress-induced DNA damage in breast cancer and chemoprevention with dietary flavonoid

    OpenAIRE

    Yasuda, Michiko T.; Sakakibara, Hiroyuki; Shimoi, Kayoko

    2017-01-01

    Breast cancer is one of the most commonly diagnosed female cancers and a leading cause of cancer-related death in women. Multiple factors are responsible for breast cancer and heritable factors have received much attention. DNA damage in breast cancer is induced by prolonged exposure to estrogens, such as 17?-estradiol, daily social/psychological stressors, and environmental chemicals such as polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HCAs). DNA damage induced by estroge...

  20. Sirt1 Is Required for Resveratrol-Mediated Chemopreventive Effects in Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    Constanze Buhrmann

    2016-03-01

    Full Text Available Sirt1 is a NAD+-dependent protein-modifying enzyme involved in regulating gene expression, DNA damage repair, metabolism and survival, as well as acts as an important subcellular target of resveratrol. The complex mechanisms underlying Sirt1 signaling during carcinogenesis remain controversial, as it can serve both as a tumor promoter and suppressor. Whether resveratrol-mediated chemopreventive effects are mediated via Sirt1 in CRC growth and metastasis remains unclear; which was the subject of this study. We found that resveratrol suppressed proliferation and invasion of two different human CRC cells in a dose-dependent manner, and interestingly, this was accompanied with a significant decrease in Ki-67 expression. By transient transfection of CRC cells with Sirt1-ASO, we demonstrated that the anti-tumor effects of resveratrol on cells was abolished, suggesting the essential role of this enzyme in the resveratrol signaling pathway. Moreover, resveratrol downregulated nuclear localization of NF-κB, NF-κB phosphorylation and its acetylation, causing attenuation of NF-κB-regulated gene products (MMP-9, CXCR4 involved in tumor-invasion and metastasis. Finally, Sirt1 was found to interact directly with NF-κB, and resveratrol did not suppress Sirt1-ASO-induced NF-κB phosphorylation, acetylation and NF-κB-regulated gene products. Overall, our results demonstrate that resveratrol can suppress tumorigenesis, at least in part by targeting Sirt1 and suppression of NF-κB activation.

  1. Chemical carcinogenesis and chemoprevention: Scientific priority ...

    African Journals Online (AJOL)

    Occupational cancers are now a serious concern in industrializing developing countries where exposure levels to hazardous chemicals considerably exceed regulatory limits established in industrialized countries. The association between increasing use of chemicals and associated disorders and chemoprevention or ...

  2. Designing the selenium and bladder cancer trial (SELEBLAT, a phase lll randomized chemoprevention study with selenium on recurrence of bladder cancer in Belgium

    Directory of Open Access Journals (Sweden)

    Goossens Maria E

    2012-03-01

    Full Text Available Abstract Background In Belgium, bladder cancer is the fifth most common cancer in males (5.2% and the sixth most frequent cause of death from cancer in males (3.8%. Previous epidemiological studies have consistently reported that selenium concentrations were inversely associated with the risk of bladder cancer. This suggests that selenium may also be suitable for chemoprevention of recurrence. Method The SELEBLAT study opened in September 2009 and is still recruiting all patients with non-invasive transitional cell carcinoma of the bladder on TURB operation in 15 Belgian hospitals. Recruitment progress can be monitored live at http://www.seleblat.org. Patients are randomly assigned to selenium yeast (200 μg/day supplementation for 3 years or matching placebo, in addition to standard care. The objective is to determine the effect of selenium on the recurrence of bladder cancer. Randomization is stratified by treatment centre. A computerized algorithm randomly assigns the patients to a treatment arm. All study personnel and participants are blinded to treatment assignment for the duration of the study. Design The SELEnium and BLAdder cancer Trial (SELEBLAT is a phase III randomized, placebo-controlled, academic, double-blind superior trial. Discussion This is the first report on a selenium randomized trial in bladder cancer patients. Trial registration ClinicalTrials.gov identifier: NCT00729287

  3. Emerging therapeutic agents for lung cancer

    Directory of Open Access Journals (Sweden)

    Bhagirathbhai Dholaria

    2016-12-01

    Full Text Available Abstract Lung cancer continues to be the most common cause of cancer-related mortality worldwide. Recent advances in molecular diagnostics and immunotherapeutics have propelled the rapid development of novel treatment agents across all cancer subtypes, including lung cancer. Additionally, more pharmaceutical therapies for lung cancer have been approved by the US Food and Drug Administration in the last 5 years than in previous two decades. These drugs have ushered in a new era of lung cancer managements that have promising efficacy and safety and also provide treatment opportunities to patients who otherwise would have no conventional chemotherapy available. In this review, we summarize recent advances in lung cancer therapeutics with a specific focus on first in-human or early-phase I/II clinical trials. These drugs either offer better alternatives to drugs in their class or are a completely new class of drugs with novel mechanisms of action. We have divided our discussion into targeted agents, immunotherapies, and antibody drug conjugates for small cell lung cancer (SCLC and non-small-cell lung cancer (NSCLC. We briefly review the emerging agents and ongoing clinical studies. We have attempted to provide the most current review on emerging therapeutic agents on horizon for lung cancer.

  4. Chemopreventive effect of chalcone derivative, L2H17, in colon cancer development.

    Science.gov (United States)

    Xu, Shanmei; Chen, Minxiao; Chen, Wenbo; Hui, Junguo; Ji, Jiansong; Hu, Shuping; Zhou, Jianmin; Wang, Yi; Liang, Guang

    2015-11-09

    Colon cancer is the third most commonly diagnosed cancer and the second leading cause of cancer mortality worldwide. Chalcone and its derivatives are reported to exhibit anti-cancer effects in several cancer cell lines, including colon cancer cells. In addition, chalcones have advantages such as poor interaction with DNA and low risk of mutagenesity. In our previous study, a group of chalcone derivatives were synthesized and exhibited strong anti-inflammatory activities. In this study, we evaluated the anti-cancer effects of the chalcone derivative, L2H17, in colon cancer cells. The cytotoxicities of L2H17 on various colon cancer cell lines were investigated by MTT and clonogenic assay. Cell cycle and apoptosis analysis were performed to evaluate the molecular mechanism of L2H17-mediated inhibition of tumor growth. Also, scratch wound and matrigel invasion experiments were performed to estimate the cell migration and invasion after L2H17 treatment. Finally, we observed the anti-colon cancer effects of L2H17 in vivo. Our data show that compound L2H17 exhibited selective cytotoxic effect on colon cancer cells, via inducing G0/G1 cell cycle arrest and apoptosis in CT26.WT cells. Furthermore, L2H17 treatment decreased cell migration and invasion of CT26.WT cells. In addition, L2H17 possessed marked anti-tumor activity in vivo. The molecular mechanism of L2H17-mediated inhibition of tumor promotion and progression were function through inactivated NF-κB and Akt signaling pathways. All these findings show that L2H17 might be a potential growth inhibitory chalcones derivative for colon cancer cells.

  5. Terpenoids as anti-colon cancer agents - A comprehensive review on its mechanistic perspectives.

    Science.gov (United States)

    Sharma, Sharada H; Thulasingam, Senthilkumar; Nagarajan, Sangeetha

    2017-01-15

    Multistep model of colon carcinogenesis has provided the framework to advance our understanding of the molecular basis of colon cancer. This multistage process of carcinogenesis takes a long period to transform from a normal epithelial cell to invasive carcinoma. Thus, it provides enough time to intervene the process of carcinogenesis especially through dietary modification. In spite of the in-depth understanding of the colon cancer etiology and pathophysiology and its association with diet, colon cancer remains a major cause of cancer mortality worldwide. Phytochemicals and their derivatives are gaining attention in cancer prevention and treatment strategies because of cancer chemotherapy associated adverse effects. Being the largest group of phytochemicals traditionally used for medicinal purpose in India and China, terpenoids are recently being explored as anticancer agents. Anticancer properties of terpenoids are associated with various mechanisms like counteraction of oxidative stress, potentiating endogenous antioxidants, improving detoxification potential, disrupting cell survival pathways and inducing apoptosis. This review gives a comprehensive idea of naturally occurring terpenoids as useful agents for the prevention of colon cancer with reference to their classes, sources and molecular targets. Based on the explored molecular targets further research in colon cancer chemoprevention is warranted. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Chemopreventive and chemotherapeutic effects of intravesical silibinin against bladder cancer by acting on mitochondria

    National Research Council Canada - National Science Library

    Zeng, Jin; Sun, Yi; Wu, Kaijie; Li, Lei; Zhang, Gang; Yang, Zenglei; Wang, Zhiqiang; Zhang, Dong; Xue, Yan; Chen, Yule; Zhu, Guodong; Wang, Xinyang; He, Dalin

    2011-01-01

    .... A search for more effective and less toxic intravesical agents is urgently needed. We previously found the in vitro apoptotic effects of silibinin, a natural flavonoid, on high-risk bladder carcinoma cells...

  7. Ultra-flexible nanocarriers for enhanced topical delivery of a highly lipophilic antioxidative molecule for skin cancer chemoprevention.

    Science.gov (United States)

    Boakye, Cedar H A; Patel, Ketan; Doddapaneni, Ravi; Bagde, Arvind; Behl, Gautam; Chowdhury, Nusrat; Safe, Stephen; Singh, Mandip

    2016-07-01

    In this study, we developed cationic ultra-flexible nanocarriers (UltraFLEX-Nano) to surmount the skin barrier structure and to potentiate the topical delivery of a highly lipophilic antioxidative diindolylmethane derivative (DIM-D) for the inhibition of UV-induced DNA damage and skin carcinogenesis. UltraFLEX-Nano was prepared with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, 1,2-dioleoyl-3-trimethylammonium-propane, cholesterol and tween-80 by ethanolic injection method; was characterized by Differential Scanning Calorimetric (DSC), Fourier Transform Infrared (FT-IR) and Atomic Force Microscopic (phase-imaging) analyses and permeation studies were performed in dermatomed human skin. The efficacy of DIM-D-UltraFLEX-Nano for skin cancer chemoprevention was evaluated in UVB-induced skin cancer model in vivo. DIM-D-UltraFLEX-Nano formed a stable mono-dispersion (110.50±0.71nm) with >90% encapsulation of DIM-D that was supported by HPLC, DSC, FT-IR and AFM phase imaging. The blank formulation was non-toxic to human embryonic kidney cells. UltraFLEX-Nano was vastly deformable and highly permeable across the stratum corneum; there was significant (pskin deposition of DIM-D for UltraFLEX-Nano that was superior to PEG solution (13.83-fold). DIM-D-UltraFLEX-Nano pretreatment delayed the onset of UVB-induced tumorigenesis (2 weeks) and reduced (pskin inflammation (PCNA), epidermal hyperplasia (c-myc, CyclinD1), immunosuppression (IL10), cell survival (AKT), metastasis (Vimentin, MMP-9, TIMP1) but increase in apoptosis (p53 and p21). UltraFLEX-Nano was efficient in enhancing the topical delivery of DIM-D. DIM-D-UltraFLEX-Nano was efficacious in delaying skin tumor incidence and multiplicity in SKH mice comparable to sunscreen (SPF30). Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Combination aspirin and/or calcium chemoprevention with colonoscopy in colorectal cancer prevention: cost-effectiveness analyses.

    Science.gov (United States)

    Pence, Barbara C; Belasco, Eric J; Lyford, Conrad P

    2013-03-01

    Clinical and cohort studies have shown that low-dose aspirin and calcium are effective low-risk strategies for primary prevention of colorectal cancer (CRC). We compared the cost-effectiveness of aspirin and calcium chemoprevention used with colonoscopy for primary prevention of CRCs. Markov chain Monte Carlo simulations for a population of 100,000 persons, with a colonoscopy compliance rate of 50%, were used for the analysis. If adenomas were detected, colonoscopy was repeated every 4 years until no adenomas were evident. Data sources included adenoma transition rates, initial adenoma and CRC incidences, and treatment complication rates from existing literature. Age-adjusted U.S. standard population mortality rates were used and costs were from Medicare reimbursement data. The target population was U.S. adults, undergoing CRC screening from ages 50 to 75 years. Outcomes included incremental cost-effectiveness ratios (ICER), life-years saved (LYS), and cancer-free years saved (CFYS). The ICER per LYS for colonoscopy alone dominated compared with no screening. Compared with colonoscopy alone, colonoscopies with aspirin (ICER = $12,950/LYS) or calcium (ICER = $13,041/LYS) were the next most cost-effective strategies. ICERs per CFYS were $3,061 and $2,317 for aspirin and calcium, respectively, when added to colonoscopy. Sensitivity analyses indicated that initial prevalence of adenomas was a main determinant of prevention cost-effectiveness. Low-dose aspirin or calcium supplementation may be beneficial when added to colonoscopy, for optimum CRC prevention, at small incremental costs. Cost-effectiveness analyses suggest that aspirin and calcium in combination with colonoscopies are cost-effective for CRC prevention in average-risk populations.

  9. Melatonin, an inhibitory agent in breast cancer.

    Science.gov (United States)

    Nooshinfar, Elaheh; Safaroghli-Azar, Ava; Bashash, Davood; Akbari, Mohammad Esmaeil

    2017-01-01

    The heterogeneous nature of breast cancer makes it one of the most challenging cancers to treat. Due to the stimulatory effect of estrogen in mammary cancer progression, anti-estrogenic agents like melatonin have found their way into breast cancer treatment. Further studies confirmed a reverse correlation between nocturnal melatonin levels and the development of mammary cancer. In this study we reviewed the molecular inhibitory effects of melatonin in breast cancer therapy. To open access the articles, Google scholar and science direct were used as a motor search. We used from valid external and internal databases. To reach the search formula, we determined mean key words like breast cancer, melatonin, cell proliferation and death. To retrieval the related articles, we continuously search the articles from 1984 to 2015. The relevance and the quality of the 480 articles were screened; at least we selected 80 eligible articles about melatonin molecular mechanism in breast cancer. The results showed that melatonin not only inhibits breast cancer cell growth, but also is capable of inhibiting angiogenesis, cancer cell invasion, and telomerase activity. Interestingly this hormone is able to induce apoptosis through the suppression or induction of a wide range of signaling pathways. Moreover, it seems that the concomitant administration of melatonin with other conventional chemotherapy agents had beneficial effects for patients with breast cancer, by alleviating unfavorable effects of those agents and enhancing their efficacy. The broad inhibitory effects of melatonin in breast cancer make it a promising agent and may add it to the list of potential drugs in treatment of this cancer.

  10. The REDUCE metagram: a comprehensive prediction tool for determining the utility of dutasteride chemoprevention in men at risk for prostate cancer

    Directory of Open Access Journals (Sweden)

    Carvell eNguyen

    2012-10-01

    Full Text Available Introduction: 5-alpha reductase inhibitors can reduce the risk of prostate cancer but can be associated with significant side effects. A library of nomograms which predict the risk of clinical endpoints relevant to dutasteride treatment may help determine if chemoprevention is suited to the individual patient. Methods: Data from the REDUCE trial was used to identify predictive factors for nine endpoints relevant to dutasteride treatment. Using the treatment and placebo groups from the biopsy cohort, Cox proportional hazards and competing risks regression models were used to build 18 nomograms, whose predictive ability was measured by concordance index and calibration plots. Results: A total of 18 nomograms assessing the risks of cancer, high-grade cancer, high grade prostatic intraepithelial neoplasia (HGPIN, atypical small acinar proliferation (ASAP, erectile dysfunction (ED, acute urinary retention (AUR, gynecomastia, urinary tract infection (UTI and BPH-related surgery either on or off dutasteride were created. The nomograms for cancer, high grade cancer, ED, AUR, and BPH-related surgery demonstrated good discrimination and calibration while those for gynecomastia, UTI, HGPIN, and ASAP predicted no better than random chance. Conclusions: To aid patients in determining whether the benefits of dutasteride use outweigh the risks, we have developed a comprehensive metagram that can generate individualized risks of 9 outcomes relevant to men considering chemoprevention. Better models based on more predictive markers are needed for some of the endpoints but the current metagram demonstrates potential as a tool for patient counseling and decision making that is accessible, intuitive, and clinically relevant.

  11. Medicinal Plants and Natural Active Compounds for Cancer Chemoprevention/Chemotherapy

    National Research Council Canada - National Science Library

    Hilal Zaid; Michael Silbermann; Alaa Amash; Dan Gincel; Essam Abdel-Sattar; Nazli B. Sarikahya

    2017-01-01

    .... Box 240, Jenin, State of Palestine 3, Technion-Israel Institute of Technology, Middle East Cancer Consortium, Haifa, Israel 4, The Research Institute of the McGill University Health Centre, Montreal...

  12. Explorations of combinational therapy in cancer : targeting the tumor and its microenvironment by combining chemotherapy with chemopreventive approaches

    NARCIS (Netherlands)

    Wijngaarden, Johannes Willem van

    2011-01-01

    One of the most effective anticancer therapy still remains chemotherapy, however, both used as single agent as in combinational regimens, chemotherapy still encounters the problem of therapeutic resistance. Limitations of chemotherapy have led to the exploration of alternative anti-cancer approaches

  13. Prostate cancer chemoprevention by soy isoflavones: role of intestinal bacteria as the "second human genome".

    Science.gov (United States)

    Akaza, Hideyuki

    2012-06-01

    It has been found that the composition of intestinal microbiota can indicate the risk of disease to each individual. The concepts of biodynamics as used by the Benziger Winery in California, which treats every part of an agricultural environment as a living, breathing entity, can be usefully used in the construction of a system for cancer prevention, which seeks to use the relationship of coexistence (symbiosis) shared between people and intestinal symbiosis, that is, microbiota. Changes in the incidence rate of cancer among Japanese emigrants to Hawaii demonstrate the effect of the changes in the living environment. This leads to the hypothesis that an intake of soy-derived food products and the metabolization of the isoflavones they contain by intestinal microbiota is one of the factors for the significant difference in the incidence rate of prostate cancer among Asian and European/North American populations. It is further hypothesized that isoflavones, particularly equol, are a key factor in the difference in incidence rate between Asia and the West. It is suggested that not having equol converting bacteria in the intestine (non-equol producers) can be a risk factor for prostate cancer and that one direction for future research will be to examine the possibility of improving the intestinal environment to enable equol production. © 2012 Japanese Cancer Association.

  14. Colorectal Chemoprevention with Calcium and Vitamin D | Division of Cancer Prevention

    Science.gov (United States)

    DESCRIPTION: In this application we propose to complete CA098286, a double-blind, randomized, controlled trial of supplementation with vitamin D and/or calcium for the prevention of colorectal adenomas. The study builds on extensive epidemiological and experimental data indicating that both vitamin D and calcium have anti-neoplastic effects in the large bowel and that these agents interact, each requiring the other for full effect. |

  15. Research progress on chemopreventive effects of phytochemicals on colorectal cancer and their mechanisms.

    Science.gov (United States)

    Yin, Teng-Fei; Wang, Min; Qing, Ying; Lin, Ying-Min; Wu, Dong

    2016-08-21

    Colorectal cancer (CRC) is a type of cancer with high morbidity and mortality rates worldwide and has become a global health problem. The conventional radiotherapy and chemotherapy regimen for CRC not only has a low cure rate but also causes side effects. Many studies have shown that adequate intake of fruits and vegetables in the diet may have a protective effect on CRC occurrence, possibly due to the special biological protective effect of the phytochemicals in these foods. Numerous in vitro and in vivo studies have demonstrated that phytochemicals play strong antioxidant, anti-inflammatory and anti-cancer roles by regulating specific signaling pathways and molecular markers to inhibit the occurrence and development of CRC. This review summarizes the progress on CRC prevention using the phytochemicals sulforaphane, curcumin and resveratrol, and elaborates on the specific underlying mechanisms. Thus, we believe that phytochemicals might provide a novel therapeutic approach for CRC prevention, but future clinical studies are needed to confirm the specific preventive effect of phytochemicals on cancer.

  16. A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention.

    Science.gov (United States)

    Chen, Andrew C; Martin, Andrew J; Choy, Bonita; Fernández-Peñas, Pablo; Dalziell, Robyn A; McKenzie, Catriona A; Scolyer, Richard A; Dhillon, Haryana M; Vardy, Janette L; Kricker, Anne; St George, Gayathri; Chinniah, Niranthari; Halliday, Gary M; Damian, Diona L

    2015-10-22

    Nonmelanoma skin cancers, such as basal-cell carcinoma and squamous-cell carcinoma, are common cancers that are caused principally by ultraviolet (UV) radiation. Nicotinamide (vitamin B3) has been shown to have protective effects against damage caused by UV radiation and to reduce the rate of new premalignant actinic keratoses. In this phase 3, double-blind, randomized, controlled trial, we randomly assigned, in a 1:1 ratio, 386 participants who had had at least two nonmelanoma skin cancers in the previous 5 years to receive 500 mg of nicotinamide twice daily or placebo for 12 months. Participants were evaluated by dermatologists at 3-month intervals for 18 months. The primary end point was the number of new nonmelanoma skin cancers (i.e., basal-cell carcinomas plus squamous-cell carcinomas) during the 12-month intervention period. Secondary end points included the number of new squamous-cell carcinomas and basal-cell carcinomas and the number of actinic keratoses during the 12-month intervention period, the number of nonmelanoma skin cancers in the 6-month postintervention period, and the safety of nicotinamide. At 12 months, the rate of new nonmelanoma skin cancers was lower by 23% (95% confidence interval [CI], 4 to 38) in the nicotinamide group than in the placebo group (P=0.02). Similar differences were found between the nicotinamide group and the placebo group with respect to new basal-cell carcinomas (20% [95% CI, -6 to 39] lower rate with nicotinamide, P=0.12) and new squamous-cell carcinomas (30% [95% CI, 0 to 51] lower rate, P=0.05). The number of actinic keratoses was 11% lower in the nicotinamide group than in the placebo group at 3 months (P=0.01), 14% lower at 6 months (Pnicotinamide was discontinued. Oral nicotinamide was safe and effective in reducing the rates of new nonmelanoma skin cancers and actinic keratoses in high-risk patients. (Funded by the National Health and Medical Research Council; ONTRAC Australian New Zealand Clinical Trials

  17. Dietary Glucosinolates Sulforaphane, Phenethyl Isothiocyanate, Indole-3-Carbinol/3,3'-Diindolylmethane: Anti-Oxidative Stress/Inflammation, Nrf2, Epigenetics/Epigenomics andIn VivoCancer Chemopreventive Efficacy.

    Science.gov (United States)

    Fuentes, Francisco; Paredes-Gonzalez, Ximena; Kong, Ah-Ng Tony

    2015-05-01

    Glucosinolates are a group of sulfur-containing glycosides found in many plant species, including cruciferous vegetables such as broccoli, cabbage, brussels sprouts, and cauliflower. Accumulating evidence increasingly supports the beneficial effects of dietary glucosinolates on overall health, including as potential anti-cancer agents, because of their role in the prevention of the initiation of carcinogenesis via the induction of cellular defense detoxifying/antioxidant enzymes and their epigenetic mechanisms, including modification of the CpG methylation of cancer-related genes, histone modification regulation and changes in the expression of miRNAs. In this context, the defense mechanism mediated by Nrf2-antioxidative stress and anti-inflammatory signaling pathways can contribute to cellular protection against oxidative stress and reactive metabolites of carcinogens. In this review, we summarize the cancer chemopreventive role of naturally occurring glucosinolate derivatives as inhibitors of carcinogenesis, with particular emphasis on specific molecular targets and epigenetic alterations in in vitro and in vivo human cancer animal models.

  18. Free radical scavenging, antioxidant and cancer chemoprevention by grape seed proanthocyanidin: an overview.

    Science.gov (United States)

    Bagchi, Debasis; Swaroop, Anand; Preuss, Harry G; Bagchi, Manashi

    2014-10-01

    A large number of investigations have demonstrated a broad spectrum of pharmacological and therapeutic benefits of grape seed proanthocyanidins (GSP) against oxidative stress and degenerative diseases including cardiovascular dysfunctions, acute and chronic stress, gastrointestinal distress, neurological disorders, pancreatitis, various stages of neoplastic processes and carcinogenesis including detoxification of carcinogenic metabolites. GSP exhibited potent free radical scavenging abilities in both in vitro and in vivo models. GSP exerted significant in vivo protection against structurally diverse drug and chemical-induced hepatotoxicity, cardiotoxicity, neurotoxicity, nephrotoxicity and spleentoxicity. GSP also protected against idarubicin and 4-hydroxyperoxy-cyclophosphamide-induced cytotoxicity toward human normal liver cells. GSP exhibited selective cytotoxicity toward selected human cancer cells, while enhancing the growth and viability of normal cells. GSP exhibited potent modulatory effects of pro-apoptotic and apoptotic regulatory bcl-XL, p53, c-myc, c-JUN, JNK-1 and CD36 genes. Long-term exposure to GSP may serve as a novel chemoprotectant against three stages of DMN-induced liver carcinogenesis and tumorigenesis including initiation, promotion and progression. GSP may selectively protect against oxidative stress, genomic integrity and cell death patterns in vivo. These results demonstrate that GSP may serve as a novel therapeutic intervention against carcinogenesis. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. The Chemopreventive and Chemotherapeutic Potentials of Tea Polyphenols

    Science.gov (United States)

    Thakur, Vijay S; Gupta, Karishma; Gupta, Sanjay

    2011-01-01

    Tea is the second most consumed beverage in the world reported to have multiple health benefits. Preventive and therapeutic benefits of tea polyphenols include enhanced general well being and anti-neoplastic effects. The pharmacologic action of tea is often attributed to various catechins present therein. Experiments conducted in cancer cell lines and animal models demonstrate that tea polyphenols protect against cellular damage caused by oxidative stress and altered immunity. Tea polyphenols modify various metabolic and signaling pathways in the regulation of proliferation, apoptosis, angiogenesis, and metastasis and therefore restrict clonal expansion of cancer cells. Tea polyphenols have been shown to reactivate tumor suppressors, block the unlimited replicative potential of cancer cells, and physically bind to nucleic acids involved in epigenetic alterations of gene regulation. Remarkable interest in green tea as a potential chemopreventive agent has been generated since recent epigenetic data showed that tea polyphenols have the potential to reverse epigenetic modifications which might otherwise be carcinogenic. Like green tea, black tea may also possess chemopreventive and chemotherapeutic potential; however, there is still not enough evidence available to make any conclusive statements. Here we present a brief description of tea polyphenols and discuss the findings of various in vitro and in vivo studies of the anticancer effects of tea polyphenols. Detailed discussion of various studies related to epigenetic changes caused by tea polyphenols leading to prevention of oncogenesis or cancer progression is included. Finally, we discuss on the scope and development of tea polyphenols in cancer prevention and therapy. PMID:21466438

  20. Breast Cancer Biomarkers Based on Nipple and Fine Needle Aspirates

    National Research Council Canada - National Science Library

    Russo, Irma H

    2005-01-01

    ... of the cytological normal breast epithelium of women at high risk for breast cancer. This signature will serve as an intermediate biomarker for evaluating the response of the breast to novel chemopreventive agents...

  1. Cancer chemotherapeutic agents as human teratogens.

    Science.gov (United States)

    Selig, Brady P; Furr, James R; Huey, Ryan W; Moran, Colin; Alluri, Vinod N; Medders, Gregory R; Mumm, Christina D; Hallford, H Gene; Mulvihill, John J

    2012-08-01

    Cancer is the second leading cause of death among women of reproductive age. Although the coincidence of pregnancy and cancer is rare and treatment may sometimes be safely delayed, the use of chemotherapeutic agents in pregnancy is sometimes unavoidable or inadvertent. We review the literature for the use of antineoplastic agents in single-agent and combination therapy from 1951 through June 2012. We also summarize the evidence relating to teratogenicity of disorder-specific combination chemotherapy treatments for those malignancies frequently encountered in women of childbearing age. Major endpoints were called "adverse pregnancy outcomes" (APOs), to include structural anomalies (congenital malformations), functional defects, blood or electrolyte abnormalities, stillbirths, spontaneous abortions (miscarriages), and fetal, neonatal, or maternal deaths. The registry totals 863 cases. Rates of APOs (and congenital malformations) after any exposure were 33% (16%), 27% (8%), and 25% (6%), for first, second, and third trimesters. Among the groups of cancer drugs, antimetabolites and alkylating agents have the highest rates of APOs. Mitotic inhibitors and antibiotics seem more benign. Mixed results were observed from single-agent exposure, often because of small numbers of exposures. As a whole, the alkylating agents and antimetabolites are more harmful when given as a single agent rather than as part of a regimen. First-trimester exposure poses a more permanent risk to the fetus. Systematic ascertainment of women early in pregnancy, preferably in a population base, is needed for assessment of true risks. Long-term follow-up is needed to rule out neurobehavioral effects. Copyright © 2012 Wiley Periodicals, Inc.

  2. Resveratrol analogs: promising chemopreventive agents.

    Science.gov (United States)

    Ogas, Talysa; Kondratyuk, Tamara P; Pezzuto, John M

    2013-07-01

    Although resveratrol can modulate multiple stages of carcinogenesis, by most common standards it is not a good drug candidate. Resveratrol lacks potency, high efficacy, and target specificity; it is rapidly metabolized and serum concentrations are low. Using resveratrol as a scaffold, we produced over 100 derivatives, some of which have target specificity in the nanomolar range. Aromatase inhibition was enhanced over 6000-fold by using 1,3-thiazole as the central ring of resveratrol. Optimizing the substitution pattern of the two phenyl rings and the central heterocyclic linker led to selective QR1 induction with a CD value of 87 nM. Several derivatives have been selected for evaluation of synergistic effects. Preliminary results with pairs of compounds are promising and further experiments, in a constant multidrug manner, will allow us to create polygonograms for larger combinations of derivatives. The objective is to develop a highly efficacious cocktail of derivatives based on the structure of resveratrol. © 2013 New York Academy of Sciences.

  3. Novel targeted agents for gastric cancer

    Directory of Open Access Journals (Sweden)

    Liu Lian

    2012-06-01

    Full Text Available Abstract Contemporary advancements have had little impact on the treatment of gastric cancer (GC, the world’s second highest cause of cancer death. Agents targeting human epidermal growth factor receptor mediated pathways have been a common topic of contemporary cancer research, including monoclonal antibodies (mAbs and receptor tyrosine kinase inhibitors (TKIs. Trastuzumab is the first target agent evidencing improvements in overall survival in HER2-positive (human epidermal growth factor receptor 2 gastric cancer patients. Agents targeting vascular epithelial growth factor (VEGF, mammalian target of rapamycin (mTOR, and other biological pathways are also undergoing clinical trials, with some marginally positive results. Effective targeted therapy requires patient selection based on predictive molecular biomarkers. Most phase III clinical trials are carried out without patient selection; therefore, it is hard to achieve personalized treatment and to monitor patient outcome individually. The trend for future clinical trials requires patient selection methods based on current understanding of GC biology with the application of biomarkers.

  4. Chemopreventive Effects of Azadirachta indica on Cancer Marker Indices and Ultrastructural Changes During 1,2-Dimethylhydrazine-Induced Colon Carcinogenesis in Rats.

    Science.gov (United States)

    Liu, Ning; Sun, Bo; Wu, Peiwei; Wei, Xi

    2015-09-01

    The present study elucidated the prospective of Azadirachta indica supplementation, if any, in affording chemoprevention by modulating the altered cancer markers and ultrastructural changes in DMH-induced colorectal carcinogenesis in rats. The rats were segregated into four groups viz., normal control, DMH treated, A. indica treated, and DMH+AI treated. Initiation and induction of colon carcinogenesis were achieved through weekly subcutaneous injections of DMH (30 mg/kg body weight) for both 10 and 20 weeks. A. indica extract was supplemented to rats at a dose rate of 100 mg/kg body weight of animals thrice a week on alternative days, ad libitum for two different time durations of 10 and 20 weeks. The study observed a significant increase in the number of aberrant crypt foci in colons of DMH-treated rats at both the time intervals which were decreased significantly upon AI supplementation. Also, a significant increase was seen in the enzyme activity of alkaline phosphatase, which, however, was moderated upon AI administration to DMH-treated rats. Changes in the ultrastructural architecture of colonic cells were apparent following both the treatment schedules of DMH; however, the changes were prominent following 20 weeks of DMH treatment. The most obvious changes were seen in the form of altered nuclear shape and disruption of cellular integrity, which were appreciably improved upon AI supplementation. In conclusion, the study shows the chemopreventive abilities of AI against DMH-induced colorectal carcinogenesis in rats.

  5. Teriflunomide (Leflunomide Promotes Cytostatic, Antioxidant, and Apoptotic Effects in Transformed Prostate Epithelial Cells: Evidence Supporting a Role for Teriflunomide in Prostate Cancer Chemoprevention

    Directory of Open Access Journals (Sweden)

    Numsen Hail, Jr

    2010-06-01

    Full Text Available Teriflunomide (TFN is an inhibitor of de novo pyrimidine synthesis and the active metabolite of leflunomide. Leflunomide is prescribed to patients worldwide as an immunomodulatory and anti-inflammatory disease-modifying prodrug. Leflunomide inhibited the growth of human prostate cancer xenographs in mice, and leflunomide or TFN promoted cytostasis and/or apoptosis in cultured cells. These findings suggest that TFN could be useful in prostate cancer chemoprevention. We investigated the possible mechanistic aspects of this tenet by characterizing the effects of TFN using premalignant PWR-1E and malignant DU-145 human prostate epithelial cells. TFN promoted a dose- and time-dependent cytostasis or apoptosis induction in these cells. The cytostatic effects of TFN, which were reversible but not by the presence of excess uridine in the culture medium, included diminished cellular uridine levels, an inhibition in oxygen consumption, a suppression of reactive oxygen species (ROS generation, S-phase cell cycle arrest, and a conspicuous reduction in the size and number of the nucleoli in the nuclei of these cells. Conversely, TFN's apoptogenic effects were characteristic of catastrophic mitochondrial disruption (i.e., a dissipation of mitochondrial inner transmembrane potential, enhanced ROS production, mitochondrial cytochrome c release, and cytoplasmic vacuolization and followed by DNA fragmentation. The respiration-deficient derivatives of the DU-145 cells, which are also uridine auxotrophs, were markedly resistant to the cytostatic and apoptotic effects of TFN, implicating de novo pyrimidine synthesis and mitochondrial bioenergetics as the primary targets for TFN in the respiration competent cells. These mechanistic findings advocate a role for TFN and mitochondrial bioenergetics in prostate cancer chemoprevention.

  6. Pomegranate By-Products in Colorectal Cancer Chemoprevention: Effects in Apc-Mutated Pirc Rats and Mechanistic Studies In Vitro and Ex Vivo.

    Science.gov (United States)

    Tortora, Katia; Femia, Angelo Pietro; Romagnoli, Andrea; Sineo, Irene; Khatib, Mohamad; Mulinacci, Nadia; Giovannelli, Lisa; Caderni, Giovanna

    2017-09-25

    To investigate the effect of pomegranate mesocarp, a polyphenol-rich by-product of juice production, in colorectal cancer (CRC) chemoprevention. A mesocarp decoction (PMD) is administered for 6 weeks in the diet to Pirc rats, mutated in Apc, a key-gene in CRC. Mucin-depleted foci (MDFs), as CRC biomarkers, are reduced in PMD-fed rats compared to controls (MDF/colon: 34 ± 4 versus 47 ± 3, p = 0.02). There is an increase in apoptosis in MDFs from PMD-treated rats compared to controls (2.5 ± 0.2 versus 1.6 ± 0.2, p < 0.01). To elucidate the involved mechanisms, two colon-relevant metabolites of the polyphenolic and fiber PMD components, urolithin-A (u-A) and sodium butyrate (SB), are tested alone or in combination in vitro (colon cancer cells), and ex vivo in adenoma (AD) and normal mucosa (NM) from Pirc rats. u-A 25 μm plus SB 2.5 mm (USB) causes a significant reduction in COX-2 protein expression compared to untreated controls (about -70% in cancer cell cultures, AD, and NM), and a strong increase in C-CASP-3 expression in cells (about ten times), in AD and NM (+74 and +69%). These data indicate a chemopreventive activity of PMD due, at least in part, to pro-apoptotic and anti-inflammatory action of its metabolites that could be exploited in high-risk patients. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Chemopreventive Potential of Flavonoids in Oral Squamous Cell Carcinoma in Human Studies

    Directory of Open Access Journals (Sweden)

    Elena Maria Varoni

    2013-07-01

    Full Text Available Evidence available from nutritional epidemiology has indicated an inverse association between regular consumption of fruits and vegetables and the risk of developing certain types of cancer. In turn, preclinical studies have attributed the health-promoting effects of plant foods to some groups of phytochemicals, by virtue of their many biological activities. In this survey, we briefly examine the chemopreventive potential of flavonoids and flavonoid-rich foods in human oral carcinogenesis. Despite the paucity of data from clinical trials and epidemiological studies, in comparison to in vitro/in vivo investigations, a high level of evidence has been reported for epigallocatechin gallate (EGCG and anthocyanins. These flavonoids, abundant in green tea and black raspberries, respectively, represent promising chemopreventive agents in human oral cancer.

  8. Chemopreventive evaluation of a Schiff base derived copper (II) complex against azoxymethane-induced colorectal cancer in rats.

    Science.gov (United States)

    Hajrezaie, Maryam; Hassandarvish, Pouya; Moghadamtousi, Soheil Zorofchian; Gwaram, Nura Suleiman; Golbabapour, Shahram; Najihussien, Abdrabuh; Almagrami, Amel Abdullah; Zahedifard, Maryam; Rouhollahi, Elham; Karimian, Hamed; Fani, Somaye; Kamalidehghan, Behnam; Majid, Nazia Abdul; Ali, Hapipah Mohd; Abdulla, Mahmood Ameen

    2014-01-01

    Based on the potential of Schiff base compounds to act as sources for the development of cancer chemotherapeutic agents, this in vivo study was performed to investigate the inhibitory properties of the synthetic Schiff base compound Cu(BrHAP)2 on colonic aberrant crypt foci (ACF). This study involved five groups of male rats. The negative control group was injected with normal saline once a week for 2 weeks and fed 10% Tween 20 for 10 weeks, the cancer control group was subcutaneously injected with 15 mg/kg azoxymethane once per week for two consecutive weeks, the positive control group was injected with 15 mg/kg azoxymethane once per week for two consecutive weeks and 35 mg/kg 5-fluorouracil (injected intra-peritoneally) for 4 weeks, and the experimental groups were first injected with 15 mg/kg azoxymethane once per week for two consecutive weeks and then fed 2.5 or 5 mg/kg of the Schiff base compound once a day for 10 weeks. Application of the Schiff base compound suppressed total colonic ACF formation by up to 72% to 74% (PSchiff base compound decreased the mean crypt scores in azoxymethane-treated rats. Significant elevations of superoxide dismutase, glutathione peroxidase and catalase activities and a reduction in the level of malondialdehyde were also observed. Histologically, all treatment groups exhibited significant decreases in dysplasia compared to the cancer control group (P<0.05). Immunohistochemical staining demonstrated down-regulation of the PCNA protein. Comparative western blot analysis revealed that COX-2 and Bcl2 were up-regulated and Bax was down-regulated compared with the AOM control group. The current study demonstrated that the Cu(BrHAP)2 compound has promising chemoprotective activities that are evidenced by significant decreases in the numbers of ACFs in azoxymethane-induced colon cancer.

  9. Chemopreventive effects of aloin against 1,2-dimethylhydrazine-induced preneoplastic lesions in the colon of Wistar rats.

    Science.gov (United States)

    Hamiza, O O; Rehman, M U; Khan, R; Tahir, M; Khan, A Q; Lateef, A; Sultana, S

    2014-02-01

    Chemoprevention opens new window in the prevention of all types of cancers including colon cancer. Aloin, an anthracycline in plant pigment, can be utilized as a protective agent in cancer induction. In the present study, we have evaluated the chemopreventive efficacy of aloin against 1,2-dimethylhydrazine (DMH)-induced preneoplastic lesions in the colon of Wistar rats. DMH-induced aberrant crypt foci (ACF) and mucin-depleted foci (MDF) have been used as biomarkers of colon cancer. Efficacy of aloin against the colon toxicity was evaluated in terms of biochemical estimation of antioxidant enzyme activities, lipid peroxidation, ACF, MDF, histopathological changes, and expression levels of molecular markers of inflammation and tumor promotion. Aloin pretreatment ameliorates the damaging effects induced by DMH through a protective mechanism that involved reduction in increased oxidative stress enzymes (p aloin clearly protects against chemically induced colon toxicity and acts reasonably by inducing antioxidant level, anti-inflammatory and antiproliferative markers.

  10. Comparative Analysis of Vitamin A (Retinol) Regulated Genes in African-American and Caucasian Prostate Cancer Patients

    National Research Council Canada - National Science Library

    Touma, Sue K; Gudas, Lorraine J; Nanus, David M; Tickoo, Satish K

    2007-01-01

    Vitamin A (retinol) and its related metabolites like retinoic acid (RA) have great potential in their roles as prostate cancer chemopreventive and chemotherapeutic agents by exerting regulation on cell growth and differentiation...

  11. Natural Plant Extracts as Potential Therapeutic Agents for the Treatment of Cancer.

    Science.gov (United States)

    Goyal, Shivangi; Gupta, Nidhi; Chatterjee, Sreemoyee; Nimesh, Surendra

    2017-01-01

    Cancer, the much dreaded name, is a multifactorial and genetically a difficult disease with less or so far no 100% cure available. Globally, it has become a major social concern and worsened the economical burden, with emergence of 1,658,370 new cancer cases and 589,430 cancer deaths in the United States only in 2015. In India, the scenario is no better with high cancer prevalence of around 2.5 million incidences, with over 800,000 new cases occurring each year. By 2015, WHO has predicted estimated deaths by cancer to be 700,000. The increase could be accounted to urbanization, industrialization, hectic and unhealthy lifestyle, increased life expectancy and population growth. The current treatment regimes are becoming inefficacious due to tumor heterogeneity and increased resistance to drugs. Bioactive compounds from natural resources have revolutionized the arena of drug chemistry and rapid researches in in vitro and in vivo studies are encouraging. These natural therapeutic agents have therefore, become important for the development of multi- treatment strategies to be deployed in cancer therapy. The review summarizes the various chemopreventive and bioactive compounds isolated from several herbs which have become milestone in various kinds of tumor treatments. Also emphasis is led on including latest research data obtained from animal cell culture, animal models and preclinical trials studies conducted by scientists around the world to derive potential anti-tumorigenic agents. Finally, the review examines mechanisms of action of these compounds which will add to our existing knowledge and effort to serve and enhance the current chemotherapeutic protocols.

  12. Breaking the relay in deregulated cellular signal transduction as a rationale for chemoprevention with anti-inflammatory phytochemicals

    Energy Technology Data Exchange (ETDEWEB)

    Kundu, Joydeb Kumar [National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, Shinlim-dong, Kwanak-gu, Seoul 151-742 (Korea, Republic of); Surh, Young-Joon [National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, Shinlim-dong, Kwanak-gu, Seoul 151-742 (Korea, Republic of)]. E-mail: surh@plaza.snu.ac.kr

    2005-12-11

    Center to the cancer biology is disrupted intracellular signaling network, which transmits improper signals resulting in abnormal cellular functioning. Therefore, modulation of inappropriate cell signaling cascades might be a rational approach in achieving chemoprevention. Inflammation has long been suspected to contribute to carcinogenesis. A new horizon in chemoprevention research is the recent discovery of molecular links between inflammation and cancer. Components of the cell signaling network, especially those converge on redox-sensitive transcription factor nuclear factor-{kappa}B involved in mediating inflammatory response, have been implicated in carcinogenesis. Intracellular signaling through another redox-sensitive transcription factor AP-1 and that transmitted via a more recently identified oncoprotein {beta}-catenin are also considered to be crucial for inflammation-associated cancer. Epidemiological and experimental studies have revealed that a wide variety of phytochemicals present in our daily diet are potential chemopreventive agents that can alter or correct undesired cellular functions caused by abnormal pro-inflammatory signal transmission. Modulation of cellular signaling involved in chronic inflammatory response by anti-inflammatory phytochemicals may comprise a rational and pragmatic strategy in molecular target-based chemoprevention.

  13. The chemopreventive activity of apple against carcinogenesis: antioxidant activity and cell cycle control.

    Science.gov (United States)

    Ribeiro, Flávia A P; Gomes de Moura, Carolina F; Aguiar, Odair; de Oliveira, Flavia; Spadari, Regina C; Oliveira, Nara R C; Oshima, Celina T F; Ribeiro, Daniel A

    2014-09-01

    Apples and their derivatives are rich in phytochemicals, including flavonoids (catechins, flavonols, quercetin) and phenolic acids (quercetin glycosides, catechin, epicatechin, procyanidins), vitamins, and fibers, that confer an important antioxidant property. Chemoprevention is defined by the use of natural or synthetic agents to interfere with the progression, reverse, or inhibit carcinogenesis, thereby reducing the risk of developing clinically invasive disease. The aim of this article is to present data generated from the use of apples as a chemopreventive agent in carcinogenesis using in-vivo and in-vitro test systems. Apple and its bioactive compounds can exert chemopreventive properties as a result of antioxidant activity and cell cycle control. However, future focus of research on apple such as identifying the specific phytochemical responsible for the anticarcinogenic effect, timing of consumption, and adequate amount of apples to achieve the best preventive effect using human large randomized-controlled trials is needed. Furthermore, animal studies are also relevant for better understanding the role of this fruit in human health as well as modulation of degenerative diseases such as cancer. Therefore, this area warrants further investigation as a new way of thinking, which would apply not only to apples but also to other fruit used as promising therapeutic agents against human diseases.

  14. Breast cancer risk in young women in the national breast screening programme: implications for applying NICE guidelines for additional screening and chemoprevention.

    Science.gov (United States)

    Evans, D Gareth; Brentnall, Adam R; Harvie, Michelle; Dawe, Sarah; Sergeant, Jamie C; Stavrinos, Paula; Astley, Susan; Wilson, Mary; Ainsworth, John; Cuzick, Jack; Buchan, Iain; Donnelly, Louise S; Howell, Anthony

    2014-10-01

    In the United Kingdom, women at moderate and high risk of breast cancer between the ages of 40 and 49 years are eligible for annual mammographic screening and preventive therapy with tamoxifen. Here, we estimate the numbers of women in a population eligible for this service and the proportion of breast cancers detected in this group compared with the whole population. Women screening in the National Health Service Breast Screening Programme (NHSBSP) completed a risk questionnaire. The proportion at moderate and high risk according to National Institute of Health Care Excellence (NICE) guidelines was estimated. An estimate was also made using a different model of risk estimation (Tyrer-Cuzick). The numbers of cancers detected in the moderate/high risk groups were compared with numbers detected in the whole population. Completed questionnaires were available for 4,360 women between ages 46 and 49 years. Thirty women [0.7%; 95% confidence interval (CI), 0.5-1.0%] were at high risk and 130 (3.0%, 2.5-3.5%) were at moderate risk according to NICE guidelines. Thirty-seven cancers were detected by mammography in the whole group. Five of these were found in the moderate-/high-risk group giving a 3.2-fold increase in detection compared with the standard risk group. More women were assigned to the moderate- or high-risk group using the Tyrer-Cuzick model (N = 384), but the numbers of cancers in this group were not appreciably increased (N = 8). Systematic assessment of family history in primary care or through population-based screening will identify appreciable numbers of women in their forties, eligible for additional surveillance and chemoprevention. ©2014 American Association for Cancer Research.

  15. Fungal agents isolated from cancer patients.

    Science.gov (United States)

    Alvarez Gasca, M A; Argüero Licea, B; Pliego Castañeda, A; García Tena, S

    1998-01-01

    With the aim to know the frequency of mycotic agents in patients with different types of cancer, samples were obtained from 81 patients from the Hospital de Oncología, Centro Médico Nacional Siglo XXI, IMSS from May 1995 through May 1996. In a conventional grouping seven (7) ambulatory patients were found in early stages, twenty seven (27) occasionally hospitalized patients were found in intermediate stage and forty seven (47) hospitalized patients in terminal stage of cancer. The different samples were processed through routine mycologycal methods and the following fungi species were isolated and identified: fifty four strains (58%) of Candida albicans followed by eleven strains (11.8%) of Candida tropicalis, six strains (6.45%) of Candida parapsilosis, five strains (5.37%) of Candida krusei, four strains (4.3%) of Candida humicola and five strains (5.37%) of Rodothorula rubra. From medical devices like catheter tips, drainage catheters (Pen rouse, Foley) and gallbladder catheters; four (4) strains of C. albicans, three (3) strains of Rodothorula rubra and two (2) strains of Aspergillus sp were isolated. Of the Candida non albicans it was relevant to find C. krusei more frequently than Rodothorula rubra, Aspergillus sp and Penicillum sp. The frequency of the presence of fungi increases commensurately to the advancement of the clincal stage of the cancer.

  16. Trianthema portulacastrum Linn. exerts chemoprevention of 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Bishayee, Anupam, E-mail: abishayee@auhs.edu [Department of Pharmaceutical Sciences, School of Pharmacy, American University of Health Sciences, Signal Hill, CA 90755 (United States); Mandal, Animesh [Cancer Therapeutics and Chemoprevention Group, Department of Pharmaceutical Sciences, College of Pharmacy, Northeast Ohio Medical University, Rootstown, OH 44272 (United States)

    2014-10-15

    Highlights: • Dietary administration of an ethanolic extract of aerial parts of T. portulacastrum (TPE) exhibits a striking chemopreventive effect in an experimentally induced classical animal model of breast cancer. • The mammary tumor-inhibitory effect of TPE could be achieved, at least in part, though intervention of key hallmark capabilities of tumor cells, such as abnormal cell proliferation and evasion of apoptosis. • TPE is capable of diminishing activated canonical Wnt/β-catenin signaling to exhibit antiproliferative, proapoptotic and oncostatic effects during this early-stage mammary carcinoma. • These results coupled with a safety profile of T. portulacastrum may encourage further studies to understand the full potential of this dietary plant for chemoprevention of breast cancer. - Abstract: Due to limited treatment options for advanced-stage metastatic breast cancer, a high priority should be given to develop non-toxic chemopreventive drugs. The value of various natural and dietary agents to reduce the risk of developing breast cancer is well established. Trianthema portulacastrum Linn. (Aizoaceae), a dietary and medicinal plant, has been found to exert antihepatotoxic and antihepatocarcinogenic properties in rodents. This study was initiated to investigate mechanism-based chemopreventive potential of an ethanolic extract of T. portulacastrum (TPE) against 7,12-dimethylbenz(a)anthracene (DMBA)-initiated rat mammary gland carcinogenesis, an experimental tumor model that closely resembles human breast cancer. Rats had access to a basal diet supplemented with TPE to yield three dietary doses of the extract, i.e., 50, 100 and 200 mg/kg body weight. Following two weeks of TPE treatment, mammary tumorigenesis was initiated by oral administration of DMBA (50 mg/kg body weight). At the end of the study (16 weeks after DMBA exposure), TPE exhibited a striking reduction of DMBA-induced mammary tumor incidence, total tumor burden and average tumor weight

  17. OVULATION INDUCTION AGENTS AND OVARIAN CANCER

    Directory of Open Access Journals (Sweden)

    Barbara Požlep

    2001-10-01

    Full Text Available Background. Ovarian cancer is the most frequentcause of death among gynecologic malignancies. Epidemiologicaldata show that environmental, hormonal and geneticfactors are etiologically significant. Beside the already knownrisk factors, ovulation induction agents have been reported asrisk factors in literature since 1986. Over the last two decades,ovulation induction agents have been widely used in variousassisted reproduction techniques (ART. This study focusedon the question whether in patients receiving ovulation inductionagents the risk for developing pathologic processes onthe ovaries was higher than in those not receiving them, andwhether they were related to the dose and type of ovulationinduction agent.Methods. In a prospective study 380 subjects were enrolled.The study group consisted of 280 women who had undergonean ART procedure three or more times. The control group consistedof 120 infertile women, never included in an ART procedure.All the enrolled subjects underwent the same examinations:a detailed gynecological history was taken, pelvic examinationand vaginal ultrasound were performed, and a bloodsample for tumour marker CA 125 determination was taken.Statistical analysis was done using Chi-square test, t test andlogistic regression.Results. Ultrasound examination revealed pathology on thegenital tract in 136 women in the study group and in 60 womenin the control group. Differences in the incidence of ovarian,tubal and uterine pathology were not statistically significant.The analysis of the medical records showed that the incidenceof ovarian pathology was significantly higher in thestudy than in the control group (p < 0.05. We found no correlationbetween the incidence of ovarian pathology and typeor dose of ovulation induction agent. Increased CA 125 levelswere found in 12 women. In none of the women neither malignantnor borderline malignant disease was found.Conclusions. Although the analysis of the data from medicalhistory showed

  18. Recent Advances on Inorganic Nanoparticle-Based Cancer Therapeutic Agents

    National Research Council Canada - National Science Library

    Wang, Fenglin; Li, Chengyao; Cheng, Jing; Yuan, Zhiqin

    2016-01-01

      Inorganic nanoparticles have been widely investigated as therapeutic agents for cancer treatments in biomedical fields due to their unique physical/chemical properties, versatile synthetic strategies...

  19. Chemoprevention of Radiation Induced Rat Mammary Neoplasms

    Science.gov (United States)

    Huso, David L.

    1999-01-01

    Radiations encountered in space include protons and heavy ions such as iron as well as their secondaries. The relative biological effect (RBE) of these ions is not known, particularly at the doses and dose-rates expected for planetary missions. Neutrons, are not particularly relevant to space travel, but have been found experimentally to have an increase in their RBE with decreasing dose. If a similar trend of increasing RBE with decreasing dose is present for heavy ions and protons during irradiation in space, the small doses received during space travel could potentially have substantial carcinogenic risk. Clearly more investigation of the effects of heavy ions and protons is needed before accurate risk assessment for prolonged travel in space can be done. One means to mitigate the increased risk of cancer due to radiation exposure in space is by developing effective countermeasures that can reduce the incidence of tumor development. Tamoxifen has recently been shown to be an effective chemopreventive agent in both animal models and humans for the prevention of mammary tumors. Tamoxifen is a unique drug, with a highly specific mechanism of action affecting a specific radiation-sensitive population of epithelial cells in the mammary gland. In human studies, the annual incidence of a primary tumor in the contralateral breast of women with previous breast cancer is about 8 per 1000, making them an exceedingly high-risk group for the development of breast cancer. In this high risk group, treated with tamoxifen, daily, for 2 years, the incidence of a new primary tumor in the contralateral breast was approximately one third of that noted in the non-tamoxifen treatment group. Tamoxifen antagonizes the action of estrogen by competing for the nuclear receptor complex thereby altering the association of the receptor complex and nuclear binding sites. Its effects in reducing the development of breast cancer could be accomplished by controlling clinically undetectable

  20. Identification of dithiolethiones with better chemopreventive properties than oltipraz.

    Science.gov (United States)

    Maxuitenko, Y Y; Libby, A H; Joyner, H H; Curphey, T J; MacMillan, D L; Kensler, T W; Roebuck, B D

    1998-09-01

    Oltipraz and related dithiolethiones are an important class of chemopreventive agents. Studies were undertaken to identify cancer chemopreventive dithiolethiones more active than oltipraz. Largely based upon enzyme induction activities in vitro, 17 dithiolethiones, including oltipraz, were analyzed for their ability to induce hepatic phase II enzyme activities in vivo. Of these compounds, 15 produced greater induction of NAD(P)H:quinone reductase and 11 yielded greater induction of glutathione S-transferase than oltipraz. All 17 dithiolethiones were then tested for their ability to inhibit acute hepatotoxicity by aflatoxin B1 (AFB1), which previously has been shown to be an intermediate predictor of chemopreventive activity. Rats were pretreated with dithiolethiones (0.3 mmol/kg body wt, three times a week per os) and challenged with two acutely toxic doses of AFB1 (0.5 mg/kg body wt, once daily for two successive days per os). Inhibition of hepatotoxicity was measured by changes in body weight gain during AFB1 challenge, reduction in levels of hepatic enzymes in serum and diminution of bile duct cell proliferation. Nine dithiolethiones spanning a range of responses in this toxicity screen were further tested for their ability to prevent AFB1-induced tumorigenicity, as assessed by a reduction in hepatic burden of putative preneoplastic foci. Six dithiolethiones were found to be considerably more effective than oltipraz in preventing AFB1-induced tumorigenesis. In general, dithiolethiones that were very effective in inhibition of acute hepatotoxicity were also found to be effective in prevention of hepatic tumorigenesis.

  1. A worked example of "best fit" framework synthesis: a systematic review of views concerning the taking of some potential chemopreventive agents.

    Science.gov (United States)

    Carroll, Christopher; Booth, Andrew; Cooper, Katy

    2011-03-16

    A variety of different approaches to the synthesis of qualitative data are advocated in the literature. The aim of this paper is to describe the application of a pragmatic method of qualitative evidence synthesis and the lessons learned from adopting this "best fit" framework synthesis approach. An evaluation of framework synthesis as an approach to the qualitative systematic review of evidence exploring the views of adults to the taking of potential agents within the context of the primary prevention of colorectal cancer. Twenty papers from North America, Australia, the UK and Europe met the criteria for inclusion. Fourteen themes were identified a priori from a related, existing conceptual model identified in the literature, which were then used to code the extracted data. Further analysis resulted in the generation of a more sophisticated model with additional themes. The synthesis required a combination of secondary framework and thematic analysis approaches and was conducted within a health technology assessment timeframe. The novel and pragmatic "best fit" approach to framework synthesis developed and described here was found to be fit for purpose. Future research should seek to test further this approach to qualitative data synthesis.

  2. Cancers in Australia in 2010 attributable to infectious agents.

    Science.gov (United States)

    Antonsson, Annika; Wilson, Louise F; Kendall, Bradley J; Bain, Christopher J; Whiteman, David C; Neale, Rachel E

    2015-10-01

    To estimate the proportion and numbers of cancers in Australia in 2010 attributable to infectious agents. The population attributable fraction (PAF) and number of cancers caused by hepatitis B and C viruses (HBV, HCV), Helicobacter pylori and human immunodeficiency virus (HIV) were calculated using standard formulae incorporating prevalence of infection in the Australian population, the relative risks associated with that infection and cancer incidence. For cancers with very strong associations to the infectious agent (Epstein-Barr virus [EBV], human papillomavirus [HPV] and HIV/Kaposi's sarcoma herpes virus [KSHV]), calculations were based on viral prevalence in the tumour. An estimated 3,421 cancers (2.9% of all cancers) in Australia in 2010 were attributable to infections. Infectious agents causing the largest numbers of cancers were HPV (n=1,706), H. pylori (n=793) and HBV/HCV (n=518). Cancer sites with the greatest number of cancers caused by infections were cervix (n=818), stomach (n=694) and liver (n=483). Cancers with highest proportions attributable to infectious agents were Kaposi's sarcoma (100%), cervix (100%), nasopharynx (87%), anus (84%) and vagina (70%). Infectious agents cause more than 3,000 cancers annually in Australia. Opportunities for cancer prevention through infection control are considerable, even in a 'first world' nation like Australia. © 2015 The Authors.

  3. Piperine as a potential anti-cancer agent: a Review on Preclinical studies.

    Science.gov (United States)

    Manayi, Azadeh; Nabavi, Seyed Mohammad; Setzer, William N; Jafari, Samineh

    2017-05-23

    Recently many studies showed anticancer activities of piperine, a pungent alkaloid found in black pepper and some other Piper species. We attempted to summarize acquired data that support anticancer potential of this natural agent. Piperine has been reported to possess effective chemopreventive activity. It has been studied to affect several mechanisms of action, in brief enhancing antioxidant system, increasing level and activity of detoxifying enzymes and suppressing stem cell self-renewal. Moreover, piperine has been found to inhibit proliferation and survival of various cancerous cell lines via modulating cell cycle progression and exhibiting anti-apoptotic activity, respectively. This compound has been shown to modify activity of various enzymes and transcription factors to inhibit invasion, metastasis and angiogenesis. Interestingly, piperine has exhibited antimutagenic activity and also inhibited activity and expression of multidrug resistance transporters such as P-gp and MRP-1. Besides, about all reviewed studies have reported selective cytotoxic activity of piperine on cancerous cells in compared with normal cells. Altogether, the studies completely underline promising candidacy of piperine for further development. The collected preclinical data we provided in this article can be useful in the design of future researches especially clinical trials with piperine. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Phase III randomised chemoprevention study with selenium on the recurrence of non-invasive urothelial carcinoma. The SELEnium and BLAdder cancer Trial.

    Science.gov (United States)

    Goossens, Maria E; Zeegers, Maurice P; van Poppel, Hendrik; Joniau, Steven; Ackaert, Koen; Ameye, Filip; Billiet, Ignace; Braeckman, Johan; Breugelmans, Alex; Darras, Jochen; Dilen, Kurt; Goeman, Lieven; Tombal, Bertrand; Van Bruwaene, Siska; Van Cleyenbreugel, Ben; Van der Aa, Frank; Vekemans, Kris; Buntinx, Frank

    2016-12-01

    In Belgium, bladder cancer (BC) is the fifth most common cancer in men. The per-patient lifetime cost is high. Previous epidemiological studies have consistently reported that selenium concentrations were inversely associated with the risk of BC. We therefore hypothesised that selenium may be suitable for chemoprevention of recurrence of BC. The Selenium and Bladder Cancer Trial (SELEBLAT) was an academic phase III placebo-controlled, double-blind, randomised clinical trial designed to determine the effect of selenium on recurrence of non-invasive urothelial carcinoma conducted in 14 Belgian hospitals. Patients were randomly assigned by a computer program to oral selenium yeast 200 μg once a day or placebo for three years, in addition to standard care. All study personnel and participants were blinded to treatment assignment for the duration of the study. All randomised patients were included in the intention to treat (ITT) and safety analyses. Per protocol analyses (PPAs) included all patients in the study three months after start date. Between September 18, 2009 and April 18, 2013, 151 and 141 patients were randomised in the selenium and placebo group. Patients were followed until December 31, 2015. The ITT analysis resulted in 43 (28%; 95% CI, 0.21-0.35) and 45 (32%; 95% CI, 0.24-0.40) recurrences in the selenium and placebo group. The hazard ratio (HR) was 0.85 (95% CI, 0.56-1.29; p = 0.44) while the HR for the PPA resulted in 42 and 39 (28%; 95% CI, 0.20-0.35) recurrences in the selenium and placebo group (HR = 0.96 [95% CI, 0.62-1.48]; p = 0.93). Selenium supplementation does not lower the probability of recurrence in BC patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Non-classical mechanisms of transcriptional regulation by the vitamin D receptor: insights into calcium homeostasis, immune system regulation and cancer chemoprevention.

    Science.gov (United States)

    Dimitrov, Vassil; Salehi-Tabar, Reyhaneh; An, Beum-Soo; White, John H

    2014-10-01

    Hormonal 1,25-dihydroxyvitamin D [1,25(OH)2D] signals through the nuclear vitamin D receptor (VDR), a ligand-regulated transcription factor. Gene expression profiling studies have revealed that 1,25(OH)2D signaling through the VDR can lead to activation or repression of target gene transcription in roughly equal proportions. Classically, transcriptional regulation by the VDR, similar to other nuclear receptors, has been characterized by its capacity to recognize high affinity cognate vitamin D response elements (VDREs), located in the regulatory regions of target genes. Several biochemical studies revealed that the VDRE-bound receptor recruits a series of coregulatory proteins, leading to transactivation of adjacent target genes. However, genome-wide and other analyses of VDR binding have revealed that a subset of VDR binding sites does not contain VDREs, and that VDREs are not associated with transcriptionally repressed VDR target genes. Work over the last ∼20 years and in particular recent findings have revealed a diverse array of mechanisms by which VDR can form complexes with several other classes of transcriptional activators, leading to repression of gene transcription. Moreover, these efforts have led to several insights into the molecular basis for the physiological regulation of calcium homeostasis, immune system function and cancer chemoprevention by 1,25(OH)2D/VDR signaling. This article is part of a Special Issue entitled '16th Vitamin D Workshop'. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Chemoprevention of skin cancer with 1,1-Bis (3'-indolyl-1-(aromatic methane analog through induction of the orphan nuclear receptor, NR4A2 (Nurr1.

    Directory of Open Access Journals (Sweden)

    Cedar H A Boakye

    Full Text Available BACKGROUND: The objective of this study was to demonstrate the anti-skin cancer and chemopreventive potential of 1,1-bis(3'-indolyl-1-(p-chlorophenyl methane (DIM-D using an in vitro model. METHODS: In vitro cell cytotoxicity and viability assays were carried out in A431 human epidermoid carcinoma cell line and normal human epidermal keratinocytes (NHEK respectively by crystal violet staining. Apoptosis induction in A431 cells (DIM-D treated and NHEK cells pretreated with DIM-D (2 hr prior to UVB irradiation, were assessed. The accumulation of reactive oxygen species (ROS in DIM-D pretreated NHEK cells (2 hr prior to UVB exposure was also determined. Immunocytochemistry and western blot analysis was performed to determine cleaved caspase 3 and DNA damage markers in DIM-D treated A431 cells and in DIM-D pretreated NHEK cells prior to UVB irradiation. RESULTS: The IC50 values of DIM-D were 68.7 ± 7.3, 48.3 ± 10.1 and 11.5 ± 3.1 μM whilst for Epigallocatechin gallate (EGCG were 419.1 ± 8.3, 186.1 ± 5.2 and 56.7 ± 3.1 μM for 24, 48 and 72 hr treatments respectively. DIM-D exhibited a significantly (p<0.05 greater induction of DNA fragmentation in A431 cells compared to EGCG with percent cell death of 38.9. In addition, DIM-D induced higher expression in A431 cells compared to EGCG of cleaved caspase 3 (3.0-fold vs. 2.4-fold changes, Nurr1 (2.7-fold vs. 1.7-fold changes and NFκB (1.3-fold vs. 1.1-fold changes. DIM-D also exhibited chemopreventive activity in UVB-irradiated NHEK cells by significantly (p<0.05 reducing UVB-induced ROS formation and apoptosis compared to EGCG. Additionally, DIM-D induced expression of Nurr1 but reduced expression of 8-OHdG significantly in UVB-irradiated NHEK cells compared to EGCG and UV only. CONCLUSION: Our results suggest that DIM-D exhibits Nurr1-dependent transactivation in the induction of apoptosis in A431 cells and it protects NHEK cells against UVB-induced ROS formation and DNA damage.

  7. Chemoprevention with Acetylsalicylic Acid, Vitamin D and Calcium Reduces Risk of Carcinogen-induced Lung Tumors

    DEFF Research Database (Denmark)

    Pommergaard, Hans-Christian; Burcharth, Jakob; Rosenberg, J

    2013-01-01

    Background/Aim: Research has shown that chemoprevention may be effective against the development of lung cancer. The purpose of the present study was to evaluate the effect of oral chemoprevention in a mouse model of tobacco carcinogen-induced lung tumor.......Background/Aim: Research has shown that chemoprevention may be effective against the development of lung cancer. The purpose of the present study was to evaluate the effect of oral chemoprevention in a mouse model of tobacco carcinogen-induced lung tumor....

  8. Effect of Food Sources of Natural Chemo preventive Agents on ...

    African Journals Online (AJOL)

    Objective: The work attempted to evaluate the potential of natural products containing cancer chemopreventive agents in increasing the level of some endogenous antioxidant enzymes such as Glutathione STransferase (GST), Glutathione reductase (GR), catalase, superoxide dismutase(SOD-1,2) in brain and kidney ...

  9. E. coli-Produced BMP-2 as a Chemopreventive Strategy for Colon Cancer : A Proof-of-Concept Study

    NARCIS (Netherlands)

    Yuvaraj, Saravanan; Al-Lahham, Sa'ad H.; Somasundaram, Rajesh; Figaroa, Patrick A.; Peppelenbosch, Maikel P.; Bos, Nicolaas A.

    2012-01-01

    Colon cancer is a serious health problem, and novel preventive and therapeutical avenues are urgently called for. Delivery of proteins with anticancer activity through genetically modified bacteria provides an interesting, potentially specific, economic and effective approach here. Interestingly,

  10. E. coli-Produced BMP-2 as a Chemopreventive Strategy for Colon Cancer: A Proof-of-Concept Study

    Directory of Open Access Journals (Sweden)

    Saravanan Yuvaraj

    2012-01-01

    Full Text Available Colon cancer is a serious health problem, and novel preventive and therapeutical avenues are urgently called for. Delivery of proteins with anticancer activity through genetically modified bacteria provides an interesting, potentially specific, economic and effective approach here. Interestingly, bone morphogenetic protein 2 (BMP-2 is an important and powerful tumour suppressor in the colon and is thus an attractive candidate protein for delivery through genetically modified bacteria. It has not been shown, however, that BMP production in the bacterial context is effective on colon cancer cells. Here we demonstrate that transforming E. coli with a cDNA encoding an ileal-derived mature human BMP-2 induces effective apoptosis in an in vitro model system for colorectal cancer, whereas the maternal organism was not effective in this respect. Furthermore, these effects were sensitive to cotreatment with the BMP inhibitor Noggin. We propose that prevention and treatment of colorectal cancer using transgenic bacteria is feasible.

  11. Chemopreventive activity of ellagitannins and their derivatives from black raspberry seeds on HT-29 colon cancer cells.

    Science.gov (United States)

    Cho, Hyunnho; Jung, Hana; Lee, Heejae; Yi, Hae Chang; Kwak, Ho-kyung; Hwang, Keum Taek

    2015-05-01

    Black raspberry (BRB) seeds are a major waste product after fruit processing. The seeds are abundant in ellagitannins (ET), a class of hydrolysable tannins, which are hydrolyzed to ellagic acid (EA) and further metabolized to urolithin A (UA) and urolithin B (UB), known to be bioavailable in the colon and the prostate. In this study, the anti-cancer activities of these compounds were evaluated on HT-29 colon cancer cells. ET, EA, UA and UB inhibited the proliferation of the cancer cells. EA caused a slight, but significant cell cycle arrest at the G1 phase, and urolithins caused cell cycle arrest at the G2/M phase and upregulated p21 expression. Apoptotic cells were detected by Annexin V-FITC/PI assay when treated with the compounds. Disruption in mitochondrial membrane potential and activation of caspases 8 and 9 suggest that both extrinsic and intrinsic apoptotic pathways may be involved. Activation of caspase 3 and cleavage of PARP further confirmed the induction of the apoptosis. ET, EA, UA and UB showed anti-cancer activity by arresting the cell cycle and inducing apoptosis on HT-29 human colon cancer cells. This study suggests that the BRB seeds could be a potential source of anti-cancer ET.

  12. Molecular Mechanisms Behind the Chemopreventive Effects of Anthocyanidins

    Directory of Open Access Journals (Sweden)

    De-Xing Hou

    2004-01-01

    Full Text Available Anthocyanins are polyphenolic ring-based flavonoids, and are widespread in fruits and vegetables of red-blue color. Epidemiological investigations and animal experiments have indicated that anthocyanins may contribute to cancer chemoprevention. The studies on the mechanism have been done recently at molecular level. This review summarizes current molecular bases for anthocyanidins on several key steps involved in cancer chemoprevention: (i inhibition of anthocyanidins in cell transformation through targeting mitogen-activated protein kinase (MAPK pathway and activator protein 1 (AP-1 factor; (ii suppression of anthocyanidins in inflammation and carcinogenesis through targeting nuclear factor kappa B (NF-κB pathway and cyclooxygenase 2 (COX-2 gene; (iii apoptotic induction of cancer cells by anthocyanidins through reactive oxygen species (ROS / c-Jun NH2-terminal kinase (JNK-mediated caspase activation. These data provide a first molecular view of anthocyanidins contributing to cancer chemoprevention.

  13. Nanomaterials incorporated ultrasound contrast agents for cancer theranostics.

    Science.gov (United States)

    Fu, Lei; Ke, Heng-Te

    2016-09-01

    Nanotechnology provides various nanomaterials with tremendous functionalities for cancer diagnostics and therapeutics. Recently, theranostics has been developed as an alternative strategy for efficient cancer treatment through combination of imaging diagnosis and therapeutic interventions under the guidance of diagnostic results. Ultrasound (US) imaging shows unique advantages with excellent features of real-time imaging, low cost, high safety and portability, making US contrast agents (UCAs) an ideal platform for construction of cancer theranostic agents. This review focuses on the development of nanomaterials incorporated multifunctional UCAs serving as theranostic agents for cancer diagnostics and therapeutics, via conjugation of superparamagnetic iron oxide nanoparticles (SPIOs), CuS nanoparticles, DNA, siRNA, gold nanoparticles (GNPs), gold nanorods (GNRs), gold nanoshell (GNS), graphene oxides (GOs), polypyrrole (PPy) nanocapsules, Prussian blue (PB) nanoparticles and so on to different types of UCAs. The cancer treatment could be more effectively and accurately carried out under the guidance and monitoring with the help of the achieved theranostic agents. Furthermore, nanomaterials incorporated theranostic agents based on UCAs can be designed and constructed by demand for personalized and accurate treatment of cancer, demonstrating their great potential to address the challenges of cancer heterogeneity and adaptation, which can provide alternative strategies for cancer diagnosis and therapeutics.

  14. Nanomaterials incorporated ultrasound contrast agents for cancer theranostics

    Science.gov (United States)

    Fu, Lei; Ke, Heng-Te

    2016-01-01

    Nanotechnology provides various nanomaterials with tremendous functionalities for cancer diagnostics and therapeutics. Recently, theranostics has been developed as an alternative strategy for efficient cancer treatment through combination of imaging diagnosis and therapeutic interventions under the guidance of diagnostic results. Ultrasound (US) imaging shows unique advantages with excellent features of real-time imaging, low cost, high safety and portability, making US contrast agents (UCAs) an ideal platform for construction of cancer theranostic agents. This review focuses on the development of nanomaterials incorporated multifunctional UCAs serving as theranostic agents for cancer diagnostics and therapeutics, via conjugation of superparamagnetic iron oxide nanoparticles (SPIOs), CuS nanoparticles, DNA, siRNA, gold nanoparticles (GNPs), gold nanorods (GNRs), gold nanoshell (GNS), graphene oxides (GOs), polypyrrole (PPy) nanocapsules, Prussian blue (PB) nanoparticles and so on to different types of UCAs. The cancer treatment could be more effectively and accurately carried out under the guidance and monitoring with the help of the achieved theranostic agents. Furthermore, nanomaterials incorporated theranostic agents based on UCAs can be designed and constructed by demand for personalized and accurate treatment of cancer, demonstrating their great potential to address the challenges of cancer heterogeneity and adaptation, which can provide alternative strategies for cancer diagnosis and therapeutics. PMID:27807499

  15. New TNF-alpha releasing inhibitors as cancer preventive agents from traditional herbal medicine and combination cancer prevention study with EGCG and sulindac or tamoxifen.

    Science.gov (United States)

    Fujiki, Hirota; Suganuma, Masami; Kurusu, Miki; Okabe, Sachiko; Imayoshi, Yoko; Taniguchi, Shoko; Yoshida, Takashi

    2003-01-01

    Herbal medicines are now attracting attention as potential sources of cancer preventive agents. Using inhibition of tumor necrosis factor-alpha (TNF-alpha) release assay, we studied Acer nikoense, Megusurino-ki in Japanese. Inhibitory potential was found in the leaf extract, and the main active principles were identified as geraniin and corilagin. The IC(50) values for TNF-alpha release inhibition were 43 microM for geraniin and 76 microM for corilagin, whereas that for (-)-epigallocatechin gallate (EGCG), the green tea polyphenol, as control was 26 microM. Furthermore, treatment with geraniin inhibited okadaic acid tumor promotion in a two-stage carcinogenesis experiment on mouse skin. Geraniin and corilagin are present in another well-known Japanese traditional herb, Geranium thunbergii, Genno-shoko in Japanese. Considering seasonal variations of the agents and sites of cultivation of herbs, this paper reviews the significance of geraniin as a new cancer preventive agent. In addition, based on accumulated results of green tea as a cancer preventive, we review two important results with EGCG: the synergistic effects of EGCG with sulindac or tamoxifen on cancer preventive activity in PC-9 cells, and cancer prevention of intestinal tumor development in multiple intestinal neoplasia (Min) mice by cotreatment using EGCG with sulindac. We report here new findings on additional gene expression resulting from cotreatment with EGCG and sulindac in PC-9 cells compared with gene expression by EGCG alone or sulindac alone. Overall, our results indicate that, with the continuing spread of cancer chemoprevention as a fundamental medical strategy, both clinicians and researchers should take a closer look at herbal medicine. Copyright 2002 Elsevier Science B.V.

  16. Chemopreventive properties of pinoresinol-rich olive oil involve a selective activation of the ATM-p53 cascade in colon cancer cell lines.

    Science.gov (United States)

    Fini, Lucia; Hotchkiss, Erin; Fogliano, Vincenzo; Graziani, Giulia; Romano, Marco; De Vol, Edward B; Qin, Huanying; Selgrad, Michael; Boland, C Richard; Ricciardiello, Luigi

    2008-01-01

    The Mediterranean diet is rich in extra virgin olive oil (EVOO) and associated with a lower incidence of colorectal cancer. EVOO contains phenolic extracts with potential anticarcinogenic activity. To assess the anticancer properties of EVOO phenolic extracts using in vitro models. Phenolic profiles of two different EVOOs (A and B) were determined. RKO and HCT116 (both p53 proficient), SW480 (p53 mutant) and HCT116(p53-/-) (p53 knocked out) cell lines were treated with EVOO extracts and assessed for cell viability. Apoptosis was determined by terminal deoxynucleotidyl transferase nick end labeling (TUNEL) assay and changes in Bax transcript levels. Cell cycle analysis was determined by flow cytometry and western blots. To confirm the data, analysis of cell viability and cell cycle was performed with purified pinoresinol. Chemical characterization showed that pinoresinol is the main phenol in EVOO-A, and oleocanthal predominates in EVOO-B. Only EVOO-A affected cell viability, which was significantly more pronounced in p53-proficient cells. At a concentration of 200 nM, p53-proficient cells showed increased apoptosis and G(2)/M arrest. In p53-proficient cells, ataxia telangiectasia mutated (ATM) and its downstream-controlled proteins were upregulated after treatment, with a parallel decrease of cyclin B/cdc2. Identical results on cell viability and cell cycle were obtained with purified pinoresinol, but this required a higher concentration than in EVOO-A. Our results demonstrate that pinoresinol-rich EVOO extracts have potent chemopreventive properties and specifically upregulate the ATM-p53 cascade. This result was achieved at substantially lower concentrations in EVOO than with purified pinoresinol, indicating a possible synergic effect between the various polyphenols in olive oil.

  17. Prevention of non-melanoma skin cancer.

    Science.gov (United States)

    Stratton, S P

    2001-07-01

    Basal cell and squamous cell carcinomas comprise the majority of non-melanoma skin cancers. Whereas the incidence of skin cancer is equivalent to that of all other cancers combined, non-melanoma skin cancer receives a disproportionate share of attention because mortality is relatively low. However, the impact on public health is striking. This review is intended to update readers on the current findings in research on the prevention of these diseases. Topics covered include preventive strategies targeting high-risk populations, chemoprevention (including treatment of intraepithelial neoplasia), and an overview of recent and ongoing clinical and preclinical studies involving new chemopreventive agents.

  18. incorporated thiadiazole hybrids as potential anti-breast cancer agents

    African Journals Online (AJOL)

    agents [4,5]. Some of the isatin incorporated thiazolines and benzthiazoles have shown significant anti breast cancer activity [6,7]. Therefore, there is essential to search and develop novel and potent chemotherapeutic agents that could overcome this health problem. ..... Mariana FF, Olea N. Antitumoral, mutagenic and.

  19. Chemotherapeutic prevention studies of prostate cancer

    DEFF Research Database (Denmark)

    Djavan, Bob; Zlotta, Alexandre; Schulman, Claude

    2004-01-01

    Despite advances in the detection and management of prostate cancer, this disease remains a major cause of morbidity and mortality in men. Increasing attention has focused on the role of chemoprevention for prostate cancer, ie the administration of agents that inhibit 1 or more steps in the natur...

  20. Clinical Pharmacology of Chemotherapy Agents in Older People with Cancer

    Directory of Open Access Journals (Sweden)

    Xiaoye He

    2011-01-01

    Full Text Available Populations around the world are aging, and the associated increase in cancer incidence has led to the recognition of the importance of geriatric oncology. Chronological age is a poor determinant of pharmacological response to cancer chemotherapy agents. Age-associated changes in physiology and organ function have a significant impact on the clinical pharmacology of cancer chemotherapy agents used in cancer treatment. Altered response to medicines in older people is a consequence of changes in body composition, organ function, concomitant pathophysiology, multiple medications, genetic determinants of drug response, and patient's clinical status. These issues highlight the need to individualize the management of cancer in the older people with consideration of age-related changes in the clinical pharmacology of cancer drugs, analgesics, and adjunctive therapies.

  1. Chemoprevention with chlorophyllin in individuals exposed to dietary aflatoxin.

    Science.gov (United States)

    Egner, Patricia A; Muñoz, Alvaro; Kensler, Thomas W

    2003-01-01

    Because of the multiplicative interaction between dietary aflatoxins and hepatitis B virus infection in the etiology of liver cancer, efforts to reduce the consequences of either chemical or viral component are likely to have substantial public health benefit. Chlorophyllin (CHL), a water-soluble form of chlorophyll, was recently evaluated as a chemopreventive agent in a population at high risk for exposure to aflatoxin and subsequent development of hepatocellular carcinoma. CHL, which is used extensively as a food colorant and has numerous medicinal applications, is an effective anticarcinogen in experimental models including aflatoxin-induced hepatocarcinogenesis. CHL is thought to form molecular complexes with carcinogens, thereby blocking their bioavailability. In the clinical trial, administration of CHL three times a day led to a 50% reduction in the median level of urinary excretion of aflatoxin-N(7)-guanine compared to placebo. This excreted DNA adduct biomarker is derived from the ultimate carcinogenic metabolite of aflatoxin B(1), aflatoxin-8,9-epoxide, and is associated with increased risk of developing liver cancer in prospective epidemiologic studies. Compliance in the intervention was outstanding and no toxicities were observed. Thus, CHL has been found to be a safe and effective agent suitable for use in individuals unavoidably exposed to aflatoxins. Copyright 2003 Elsevier Science B.V.

  2. Epigenetic cancer prevention mechanisms in skin cancer.

    Science.gov (United States)

    Saha, Kamalika; Hornyak, Thomas J; Eckert, Richard L

    2013-10-01

    Epigenetics is an important emerging area for study of mechanisms of cancer prevention. In recent years, it has been realized that cancer prevention agents, derived from natural dietary sources, impact cancer cell survival by modulating epigenetic processes. In the present manuscript, we review key epigenetic regulatory mechanisms and examine the impact of sulforaphane and green tea polyphenols on these processes. We also discuss available information on the epigenetics in the context of skin cancer. These studies indicate that diet-derived chemopreventive agents modulate DNA methylation status and histone modification via multiple processes and point to additional areas for study of epigenetic mechanisms in skin cancer.

  3. Molecular Targets of TRAIL-Sensitizing Agents in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Giovanni Monteleone

    2012-06-01

    Full Text Available Tumor necrosis factor (TNF-related apoptosis inducing ligand (TRAIL, a member of the TNF superfamily, interacts with its functional death receptors (DRs and induces apoptosis in a wide range of cancer cell types. Therefore, TRAIL has been considered as an attractive agent for cancer therapy. However, many cancers are resistant to TRAIL-based therapies mainly due to the reduced expression of DRs and/or up-regulation of TRAIL pathway-related anti-apoptotic proteins. Compounds that revert such defects restore the sensitivity of cancer cells to TRAIL, suggesting that combined therapies could help manage neoplastic patients. In this article, we will focus on the TRAIL-sensitizing effects of natural products and synthetic compounds in colorectal cancer (CRC cells and discuss the molecular mechanisms by which such agents enhance the response of CRC cells to TRAIL.

  4. Pyrrole alkaloids with potential cancer chemopreventive activity isolated from a goji berry-contaminated commercial sample of African mango.

    Science.gov (United States)

    Li, Jie; Pan, Li; Naman, C Benjamin; Deng, Ye; Chai, Heebyung; Keller, William J; Kinghorn, A Douglas

    2014-06-04

    Bioassay-guided fractionation of a commercial sample of African mango (Irvingia gabonensis) that was later shown to be contaminated with goji berry (Lycium sp.) led to the isolation of a new pyrrole alkaloid, methyl 2-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl]propanoate, 1, along with seven known compounds, 2-8. The structures of the isolated compounds were established by analysis of their spectroscopic data. The new compound 1g showed hydroxyl radical-scavenging activity with an ED50 value of 16.7 μM, whereas 4-[formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoic acid (2) was active in both the hydroxyl radical-scavenging (ED50 11.9 μM) and quinone reductase-induction [CD (concentration required to double QR activity) 2.4 μM)] assays used. The isolated compounds were shown to be absent in a taxonomically authenticated African mango sample but present in three separate authentic samples of goji berry (Lycium barbarum) using LC-MS and (1)H NMR fingerprinting analysis, including one sample that previously showed inhibitory activity in vivo in a rat esophageal cancer model induced with N-nitrosomethylbenzylamine. Additionally, microscopic features characteristic of goji berry were observed in the commercial African mango sample.

  5. Design, synthesis, and biological evaluation of resveratrol analogues as aromatase and quinone reductase 2 inhibitors for chemoprevention of cancer

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Bin; Hoshino, Juma; Jermihov, Katie; Marler, Laura; Pezzuto, John M.; Mesecar, Andrew D.; Cushman, Mark (Hawaii); (Purdue); (UIC)

    2012-07-11

    A series of new resveratrol analogues were designed and synthesized and their inhibitory activities against aromatase were evaluated. The crystal structure of human aromatase (PDB 3eqm) was used to rationalize the mechanism of action of the aromatase inhibitor 32 (IC{sub 50} 0.59 {mu}M) through docking, molecular mechanics energy minimization, and computer graphics molecular modeling, and the information was utilized to design several very potent inhibitors, including compounds 82 (IC{sub 50} 70 nM) and 84 (IC{sub 50} 36 nM). The aromatase inhibitory activities of these compounds are much more potent than that for the lead compound resveratrol, which has an IC{sub 50} of 80 {mu}M. In addition to aromatase inhibitory activity, compounds 32 and 44 also displayed potent QR2 inhibitory activity (IC{sub 50} 1.7 {mu}M and 0.27 {mu}M, respectively) and the high-resolution X-ray structures of QR2 in complex with these two compounds provide insight into their mechanism of QR2 inhibition. The aromatase and quinone reductase inhibitors resulting from these studies have potential value in the treatment and prevention of cancer.

  6. Castanea sativa Mill. bark extract exhibits chemopreventive properties triggering extrinsic apoptotic pathway in Jurkat cells.

    Science.gov (United States)

    Lenzi, Monia; Malaguti, Marco; Cocchi, Veronica; Hrelia, Silvana; Hrelia, Patrizia

    2017-05-05

    Chemoprevention represents the possibility to prevent, stop or reverse the cancerogenetic process. In this context the interest towards natural extracts and botanical drugs has constantly grown due to their phytochemical content. Castanea sativa Mill. (CSM) extracts showed to exert positive effect in the prevention/counteraction of chronic/degenerative diseases, therefore, we evaluated the potential chemopreventive effect of CSM bark extract. Flow cytometry (FCM) analyses of Jurkat cells treated with CSM bark extract (0-500 μg·mL -1 ) for 24-72 h allowed evaluating its cytotoxicity and ability to induce apoptosis through the intrinsic or extrinsic pathways. Moreover, to evaluate CSM bark extract selectivity towards cancer cells, its cytotoxic and pro-apoptotic effect was also evaluated in human peripheral blood lymphocytes (PBL). CSM bark extract induced apoptosis in Jurkat cells in a dose- and time- dependent manner activating the extrinsic pathways as evidenced by the increase of activated caspase-8 positive cells. Moreover, IC 50 calculated after 24 h treatment resulted 304 and 128 μg·mL -1 in PBL and Jurkat cells respectively. Our data suggest that CSM bark extract might be considered an interesting potential anti-cancer agent, since it induces apoptosis in cancer cells without appreciable cytotoxic effects on non-transformed cells.

  7. Selenium as a cancer preventive agent

    Science.gov (United States)

    Most epidemiological studies have shown inverse associations of selenium (Se) status and cancer risk. Almost all experimental animal studies have shown that supranutritional exposures of Se can reduce tumor yield. Each of the limited number of clinical intervention trials conducted to date has found...

  8. Recent Advances on Inorganic Nanoparticle-Based Cancer Therapeutic Agents

    Directory of Open Access Journals (Sweden)

    Fenglin Wang

    2016-11-01

    Full Text Available Inorganic nanoparticles have been widely investigated as therapeutic agents for cancer treatments in biomedical fields due to their unique physical/chemical properties, versatile synthetic strategies, easy surface functionalization and excellent biocompatibility. This review focuses on the discussion of several types of inorganic nanoparticle-based cancer therapeutic agents, including gold nanoparticles, magnetic nanoparticles, upconversion nanoparticles and mesoporous silica nanoparticles. Several cancer therapy techniques are briefly introduced at the beginning. Emphasis is placed on how these inorganic nanoparticles can provide enhanced therapeutic efficacy in cancer treatment through site-specific accumulation, targeted drug delivery and stimulated drug release, with elaborations on several examples to highlight the respective strategies adopted. Finally, a brief summary and future challenges are included.

  9. The role of chronic inflammation in the development of gastrointestinal cancers: reviewing cancer prevention with natural anti-inflammatory intervention.

    Science.gov (United States)

    Lee, Ho-Jae; Park, Jong-Min; Han, Young Min; Gil, Hong Kwon; Kim, Jinhyung; Chang, Ji Young; Jeong, Migyeong; Go, Eun-Jin; Hahm, Ki Baik

    2016-01-01

    Inflammatory mediators alter the local environment of tumors, known as the tumor microenvironment. Mechanistically, chronic inflammation induces DNA damage, but understanding this hazard may help in the search for new chemopreventive agents for gastrointestinal (GI) cancer which attenuate inflammation. In the clinic, GI cancer still remains a major cause of cancer-associated mortality, chemoprevention with anti-inflammatory agents is thought to be a realistic approach to reduce GI cancer. Proton pump inhibitors, monoclonal antibodies targeting tumor necrosis factor-alpha, anti-sense targeted smad7 and non-steroidal anti-inflammatory agents have been investigated for their potential to prevent inflammation-based GI cancer. Besides these, a wide variety of natural products have also shown potential for the prevention of GI cancer. In this review, the authors will provide insights to explain the mechanistic connection between inflammation and GI cancer, as well as describe a feasible cancer prevention strategy based on anti-inflammatory treatments.

  10. Efficacy of geraniol but not of β-ionone or their combination for the chemoprevention of rat colon carcinogenesis

    Directory of Open Access Journals (Sweden)

    A. Vieira

    2011-06-01

    Full Text Available β-ionone (βI, a cyclic isoprenoid, and geraniol (GO, an acyclic monoterpene, represent a promising class of dietary chemopreventive agents against cancer, whose combination could result in synergistic anticarcinogenic effects. The chemopreventive activities of βI and GO were evaluated individually or in combination during colon carcinogenesis induced by dimethylhydrazine in 48 3-week-old male Wistar rats (12 per group weighing 40-50 g. Animals were treated for 9 consecutive weeks with βI (16 mg/100 g body weight, GO (25 mg/100 g body weight, βI combined with GO or corn oil (control. Number of total aberrant crypt foci (ACF and of ACF ≥4 crypts in the distal colon was significantly lower in the GO group (66 ± 13 and 9 ± 2, respectively compared to control (102 ± 9 and 17 ± 3 and without differences in the βI (91 ± 11 and 14 ± 3 and βI+GO groups (96 ± 5 and 19 ± 2. Apoptosis level, identified by classical apoptosis morphological criteria, in the distal colon was significantly higher in the GO group (1.64 ± 0.06 apoptotic cells/mm² compared to control (0.91 ± 0.07 apoptotic cells/mm². The GO group presented a 0.7-fold reduction in Bcl-2 protein expression (Western blot compared to control. Colonic mucosa concentrations of βI and GO (gas chromatography/mass spectrometry were higher in the βI and GO groups, respectively, compared to the control and βI+GO groups. Therefore, GO, but not βI, represents a potential chemopreventive agent in colon carcinogenesis. Surprisingly, the combination of isoprenoids does not represent an efficient chemopreventive strategy.

  11. Red Wine Polyphenols for Cancer Prevention

    Directory of Open Access Journals (Sweden)

    Yuanjiang Pan

    2008-05-01

    Full Text Available Conventional cancer therapies, the second leading cause of death worldwide, result in serious side effects and, at best, merely extend the patient's lifespan by a few years. Searching for effective prevention is of high priority in both basic and clinical sciences. In recent decades natural products have been considered to be an important source of cancer chemopreventive agents. Red wine polyphenols, which consisted of various powerful antioxidants such as flavonoids and stilbenes, have been implicated in cancer prevention and that promote human health without recognizable side effects. Since resveratrol, a major component of red wine polyphenols, has been studied and reviewed extensively for its chemopreventive activity to interfere with the multi-stage carcinogenesis, this review focuses on recent progress in studies on cancer chemopreventive activities of red wine polyphenol extracts and fractions as well as other red wine polyphenols, like procyanidin B5 analogues and myricetin.

  12. Vaccinia virus, a promising new therapeutic agent for pancreatic cancer.

    Science.gov (United States)

    Al Yaghchi, Chadwan; Zhang, Zhongxian; Alusi, Ghassan; Lemoine, Nicholas R; Wang, Yaohe

    2015-01-01

    The poor prognosis of pancreatic cancer patients signifies a need for radically new therapeutic strategies. Tumor-targeted oncolytic viruses have emerged as attractive therapeutic candidates for cancer treatment due to their inherent ability to specifically target and lyse tumor cells as well as induce antitumor effects by multiple action mechanisms. Vaccinia virus has several inherent features that make it particularly suitable for use as an oncolytic agent. In this review, we will discuss the potential of vaccinia virus in the management of pancreatic cancer in light of our increased understanding of cellular and immunological mechanisms involved in the disease process as well as our extending knowledge in the biology of vaccinia virus.

  13. [Environmental carcinogenic agents and cancer prevention: risk assessment and management].

    Science.gov (United States)

    Tsugane, Shoichiro

    2013-11-01

    Many agents in our environment have been established as being carcinogenic, and in most cases, the carcinogenic properties of these agents were identified because of high-dose occupational or accidental exposure. Risk characterization, taking into account the dose-response relationship, and exposure assessment are essential for risk assessment and subsequent cancer prevention. Based on scientific risk assessment, risk management should be conducted practically by considering the economic, social, political, and other technical issues and by balancing the risks and benefits. Asbestos and environmental tobacco smoke are typical examples of established carcinogenic agents in the general environment, contributing to low-dose exposure. Further epidemiological studies are required to investigate the carcinogenicity of low-dose exposure to known carcinogenic agents such as arsenic and cadmium through dietary intake, radiation via medical and natural exposure, and air pollution due to diesel exhaust. In contrast, occupational chemical exposure to 1,2-dichloropropane and/or dichloromethane, whose carcinogenicity had not been established, was suggested to cause cholangiocarcinoma among workers involved in offset color proof-printing only after a rare situation of high-dose exposure was unveiled. Continuous monitoring of unusual cancer occurrences in target populations such as workers in occupational and regional settings as well as exposure reduction to suspected carcinogenic agents to levels as low as reasonably achievable is essential for reducing the risk of cancer due to environmental carcinogens.

  14. Rational Choice of Antiemetic Agents during Cancer Chemotherapy

    Science.gov (United States)

    Brigden, Malcolm L.; Wilson, Kenneth S.; Barnett, Jeffrey B.

    1983-01-01

    Nausea and vomiting are major limitations in cancer chemotherapy. Individual susceptibility to nausea varies enormously. There is no ideal antiemetic, but some work with some chemotherapeutic agents, and some are more effective in younger patients. This article describes a flexible, stepped approach using the phenothiazines, metoclopramide, cannabinoids, anticholinergics, antihistamines and others. PMID:21283402

  15. Methylselenium and Prostate Cancer Apoptosis

    Science.gov (United States)

    2003-02-01

    have Methylselenol Generation been shown to cause G1 arrest in cancer epithelial Purified METase of Pseudomonas putida (catalog 4! cells [7-9] and in...methylselenol can reach the submicromolar with carcinoma of the skin: A randomized controlled trial. 120 WANG ETAL. Nutritional Prevention of Cancer Study... Nutrition and cancer prevention. New York: 229-236. Kluwer/Plenum Publishers, 2000. p 131-145. 19. Combs GF Jr, GrayWP. Chemopreventive agents: Selenium. 10

  16. Chemopreventive effect of raw and cooked lentils (Lens culinaris L) and soybeans (Glycine max) against azoxymethane-induced aberrant crypt foci.

    Science.gov (United States)

    Faris, Mo'ez Al-Islam E; Takruri, Hamed R; Shomaf, Maha S; Bustanji, Yasser K

    2009-05-01

    Although lentils (Lens culinaris L) contain several bioactive compounds that have been linked to the prevention of cancer, the in vivo chemopreventive ability of lentils against chemically induced colorectal cancer has not been examined. Our present study examined the hypothesis that lentils could suppress the early carcinogenesis in vivo by virtue of their bioactive micro- and macroconstituents and that culinary thermal treatment could affect their chemopreventive potential. To accomplish this goal, we used raw whole lentils (RWL), raw split lentils (RSL), cooked whole lentils (CWL), and cooked split lentils (CSL). Raw soybeans (RSB; Glycine max) were used for the purpose of comparison with a well-studied chemopreventive agent. Sixty weanling Fischer 344 male rats, 4 to 5 weeks of age, were randomly assigned to 6 groups (10 rats/group): the control group (C) received AIN-93G diet, and treatment leguminous groups of RWL, CWL, RSL, CSL, and RSB received the treatment diets containing AIN-93G+5% of the above-mentioned legumes. After acclimatization for 1 week (at 5th to 6th week of age), all animals were put on the control and treatment diets separately for 5 weeks (from 6th to 11th week of age). At the end of the 5th week of feeding (end of 11th week of age), all rats received 2 subcutaneous injections of azoxymethane carcinogen at 15 mg/kg rat body weight per dose once a week for 2 consecutive weeks. After 17 weeks of the last azoxymethane injection (from 12th to 29th week of age), all rats were euthanized. Chemopreventive ability was assessed using colonic aberrant crypt foci and activity of hepatic glutathione-S-transferases. Significant reductions (P lentils might be protective against colon carcinogenesis and that hydrothermal treatment resulted in an improvement in the chemopreventive potential for the whole lentils.

  17. Quimioprevención del Cáncer de Mama: Ensayos clínicos en la prevención farmacológica Chemoprevention of breast cancer. Clinical trials in pharmacological prevention

    Directory of Open Access Journals (Sweden)

    Javier J. Ricart

    2004-02-01

    Full Text Available El presente artículo trata sobre los ensayos clínicos presentados en quimioprevención del cáncer mamario. Hasta la fecha las drogas más estudiadas han sido los Moduladores Selectivos de los Receptores de Estrógenos (SERMs. Cuatro estudios aleatorizados de tamoxifeno versus placebo fueron publicados y dos con raloxifeno están en curso. Dos de los estudios con tamoxifeno mostraron una reducción de incidencia de cáncer mamario entre el 30 y el 50%, sin embargo otros dos trabajos no mostraron diferencias estadísticamente significativas. A esta controversia se le suma la incertidumbre sobre el verdadero impacto en la mortalidad que pudiera tener este tipo de terapia preventiva. Se citan además diversos estudios que evaluaron la ingesta de vitaminas y su relación con el desarrollo de tumores mamarios. Sin duda alguna el estudio y el seguimiento de los ensayos clínicos nos permitirán dilucidar qué pacientes requieren una terapia, preventiva del desarrollo de un tipo específico de cáncer, que se encuentra lejos de estar exenta de riesgos.The following review article focuses on chemoprevention clinical trials of breast cancer. To date, SERMs (Selective Estrogen Receptor Modulators have been the most studied drugs. Four randomized trials with tamoxifen vs. placebo have been performed and two with raloxifene are being carried out. Two tamoxifen trials showed between 30 and 50% reduction in breast cancer incidence. However, two other studies showed no statistical differences. Moreover, the real impact on mortality that these therapies could have is still unknown. This article includes a revision of trials that evaluated the relationship between daily vitamin intake and breast cancer. A follow up of these trials will give us answers about which patients will benefit from chemoprevention therapies.

  18. Chemopreventive efficacy of curcumin and piperine during 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis.

    Science.gov (United States)

    Manoharan, S; Balakrishnan, S; Menon, V P; Alias, L M; Reena, A R

    2009-02-01

    Oral carcinoma accounts for 40-50 percent of all cancers in India. Tobacco chewing, smoking and alcohol consumption are the major risk factors associated with the high incidence of oral cancer in India. Our aim was to investigate the chemopreventive potential of curcumin and piperine during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Oral squamous cell carcinoma was developed in the buccal pouch of Syrian golden hamsters, by painting them with 0.5 percent DMBA in liquid paraffin, three times a week for 14 weeks. The tumour incidence, tumour volume and burden were determined in the buccal pouches. The status of phase II detoxification agents, lipid peroxidation and antioxidants were estimated by specific colorimetric methods. We observed 100 percent tumour formation in DMBA-alone painted hamsters. Disturbances in the status of lipid peroxidation, antioxidants and phase II detoxification agents were noticed in DMBA-alone painted hamsters. Oral administration of curcumin (80 mg/kg body weight) and piperine (50 mg/kg body weight) to DMBA-painted hamsters on alternate days to DMBA painting for 14 weeks completely prevented the formation of oral carcinoma. Also, curcumin and piperine restored the status of lipid peroxidation, antioxidants and detoxifying agents in DMBA-painted hamsters. The chemopreventive efficacy of curcumin and piperine is probably due to their antilipidperoxidative and antioxidant potential as well as their modulating effect on the carcinogen detoxification process.

  19. Nutrient and nonnutrient components of legumes, and its chemopreventive activity: a review.

    Science.gov (United States)

    Sánchez-Chino, Xariss; Jiménez-Martínez, Cristian; Dávila-Ortiz, Gloria; Álvarez-González, Isela; Madrigal-Bujaidar, Eduardo

    2015-01-01

    Legumes in combination with other products are the staple food for a large part of the world population, especially the low-income fragment, because their seeds provide valuable amounts of carbohydrates, fiber, and proteins, and have an important composition of essential amino acids, the sulphured amino acids being the limiting ones. Furthermore, legumes also have nonnutritional compounds that may decrease the absorption of nutrients or produce toxic effects; however, it has been reported that depending on the dose, these nonnutritional compounds also have different bioactivities as antioxidant, hypolipidemic, hypoglycemic, and anticarcinogenic agents, which have been proven in scientific studies. It has been observed that in countries with a high consumption of legumes, the incidence of colorectal cancer is lower. Some studies have shown that legume seeds are an alternative chemopreventive therapy against various cancers especially colon; this was verified in various animal models of induced by azoxymethane, a colon specific carcinogenic compound, in which a diet was supplemented with different concentrations of beans, lentils, chickpeas, or soybeans, mostly. These studies have proven the anticancer activity of legumes in early stages of carcinogenesis. Therefore, it is important to review the information available to elucidate the chemopreventive mechanisms of action of legume compounds.

  20. Targeting microtubules by natural agents for cancer therapy.

    Science.gov (United States)

    Mukhtar, Eiman; Adhami, Vaqar Mustafa; Mukhtar, Hasan

    2014-02-01

    Natural compounds that target microtubules and disrupt the normal function of the mitotic spindle have proven to be one of the best classes of cancer chemotherapeutic drugs available in clinics to date. There is increasing evidence showing that even minor alteration of microtubule dynamics can engage the spindle checkpoint, arresting cell-cycle progression at mitosis and subsequently leading to cell death. Our improved understanding of tumor biology and our continued appreciation for what the microtubule targeting agents (MTAs) can do have helped pave the way for a new era in the treatment of cancer. The effectiveness of these agents for cancer therapy has been impaired, however, by various side effects and drug resistance. Several new MTAs have shown potent activity against the proliferation of various cancer cells, including resistance to the existing MTAs. Sustained investigation of the mechanisms of action of MTAs, development and discovery of new drugs, and exploring new treatment strategies that reduce side effects and circumvent drug resistance could provide more effective therapeutic options for patients with cancer. This review focuses on the successful cancer chemotherapy from natural compounds in clinical settings and the challenges that may abort their usefulness.

  1. Systematic review: molecular chemoprevention of colorectal malignancy by mesalazine.

    Science.gov (United States)

    Lyakhovich, A; Gasche, C

    2010-01-15

    Mesalazine (mesalamine) (5-ASA) is considered an anti-inflammatory drug for the treatment of inflammatory bowel disease. It is well tolerated by most patients and induces mucosal healing specifically in ulcerative colitis. Besides its anti-inflammatory properties, 5-ASA has been studied for cancer inhibitory activities as it seems to reduce colorectal cancer incidence in patients using this drug for long periods of time. However, detailed molecular mechanisms of drug action are vague. To evaluate known molecular mechanisms of 5-ASA on chemoprevention of colorectal malignancy. Systematic review with search terms '5 aminosalicylic acid, mesalazine, 5-ASA, mesalazine, molecular mechanisms, chemoprevention' between 2006 and August 2009. A total of 48 studies were retrieved that link 5-ASA chemopreventive properties to five distinct pathways. These include interference with cell cycle progression (12 references), scavenging of reactive oxygen- or nitrogen-derived metabolites (16 references), TNF-alpha/TGF-ss signalling (11 references), WNT/beta-catenin signalling (5 references) and anti-bacterial properties (4 references). In the recent years, a large amount of molecular data has accumulated supporting the notion that 5-ASA biological effects interfere with colorectal cancer development. These molecular pathways are of special interest in the search for 5-ASA's molecular target(s) and development of novel chemopreventive compounds.

  2. Natural Products as Promising Antitumoral Agents in Breast Cancer: Mechanisms of Action and Molecular Targets.

    Science.gov (United States)

    Bonofiglio, Daniela; Giordano, Cinzia; De Amicis, Francesca; Lanzino, Marilena; Andò, Sebastiano

    2016-01-01

    Extensive research over the past several decades has identified numerous dietary and phytochemical compounds that have chemopreventive potential and could represent an important source of anti-cancer lead molecules. In this scenario several nutritional factors have attracted considerable attention as modifiable risk factor in the prevention of breast cancer, the most frequently diagnosed cancer and a major cause of death among women worldwide. There is an immediate need for more effective and less toxic therapeutic and preventive strategies for breast cancers able also to counteract the recurrent phenomenon of resistance to hormonal and targeted therapy that represent the first-line treatment in the management of breast cancer patients. The present review focuses on chemopreventive and anti-cancer activities of different bioactive compounds obtained from dietary sources such as Omega-3 fatty acids, naturally present in fish, Resveratrol (3,5,40-trihydroxy-transstilbene), a phytoalexin found in grapes and Epigallocatechin Gallate, a polyphenolic compound found in green tea, or purified from medicinal plant (Oldenlandia Diffusa) and fruits (Ziziphus Jujube) highlighting their potential use in breast cancer treatment. Herein, we discuss the molecular mechanisms by which the bioactive compounds can inhibit carcinogenesis by regulating antioxidant enzyme activities, and inducing antiproliferative and apoptotic effects in different breast cancer cell lines. Understanding the mechanism of action of dietary compounds or traditionally used herbs having potential preventive and therapeutic effects on cancer may provide a rationale for further translational studies. This review emphasizes the importance, in the next future, of a proper scientific validation of these natural bioactive compounds for clinical use in the therapeutic portfolio for breast cancer.

  3. Recombinant mumps virus as a cancer therapeutic agent

    Directory of Open Access Journals (Sweden)

    Arun Ammayappan

    2016-01-01

    Full Text Available Mumps virus belongs to the family of Paramyxoviridae and has the potential to be an oncolytic agent. Mumps virus Urabe strain had been tested in the clinical setting as a treatment for human cancer four decades ago in Japan. These clinical studies demonstrated that mumps virus could be a promising cancer therapeutic agent that showed significant antitumor activity against various types of cancers. Since oncolytic virotherapy was not in the limelight until the beginning of the 21st century, the interest to pursue mumps virus for cancer treatment slowly faded away. Recent success stories of oncolytic clinical trials prompted us to resurrect the mumps virus and to explore its potential for cancer treatment. We have obtained the Urabe strain of mumps virus from Osaka University, Japan, which was used in the earlier human clinical trials. In this report we describe the development of a reverse genetics system from a major isolate of this Urabe strain mumps virus stock, and the construction and characterization of several recombinant mumps viruses with additional transgenes. We present initial data demonstrating these recombinant mumps viruses have oncolytic activity against tumor cell lines in vitro and some efficacy in preliminary pilot animal tumor models.

  4. Recombinant mumps virus as a cancer therapeutic agent.

    Science.gov (United States)

    Ammayappan, Arun; Russell, Stephen J; Federspiel, Mark J

    2016-01-01

    Mumps virus belongs to the family of Paramyxoviridae and has the potential to be an oncolytic agent. Mumps virus Urabe strain had been tested in the clinical setting as a treatment for human cancer four decades ago in Japan. These clinical studies demonstrated that mumps virus could be a promising cancer therapeutic agent that showed significant antitumor activity against various types of cancers. Since oncolytic virotherapy was not in the limelight until the beginning of the 21(st) century, the interest to pursue mumps virus for cancer treatment slowly faded away. Recent success stories of oncolytic clinical trials prompted us to resurrect the mumps virus and to explore its potential for cancer treatment. We have obtained the Urabe strain of mumps virus from Osaka University, Japan, which was used in the earlier human clinical trials. In this report we describe the development of a reverse genetics system from a major isolate of this Urabe strain mumps virus stock, and the construction and characterization of several recombinant mumps viruses with additional transgenes. We present initial data demonstrating these recombinant mumps viruses have oncolytic activity against tumor cell lines in vitro and some efficacy in preliminary pilot animal tumor models.

  5. Natural Anti-Cancer Agents: Implications in Gemcitabine-Resistant Pancreatic Cancer Treatment.

    Science.gov (United States)

    Marasini, Bishal; Sahu, Ravi P

    2017-01-01

    Pancreatic cancer is one of the most lethal malignancies accounting for the fourth leading cause of cancer-related deaths in the United States. Among several explored anticancer agents, Gemcitabine, a nucleoside analogue remained a front line chemotherapeutic agent for the treatment of pancreatic cancer. However, gemcitabine exerts a low response rate with limited progression free survival in patients due to cellular resistance of pancreatic tumors to this therapy. Several chemotherapeutic agents have been explored in combination with gemcitabine against pancreatic cancer with overall mixed responses and survival rates. Naturally occurring dietary agents possess promising anticancer properties and have been shown to target various oncogenic signaling pathways in in-vitro and in-vivo pancreatic cancer models. Multiple studies using natural compounds have shown increased therapeutic efficacy of gemcitabine in pancreatic cancer models. This review is focused on recent updates on cellular, preclinical and clinical studies utilizing natural anticancer agents with gemcitabine against pancreatic cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Novel agents in the management of lung cancer.

    LENUS (Irish Health Repository)

    Kennedy, B

    2012-01-31

    Lung cancer is the leading cause of cancer death worldwide. Survival remains poor as approximately 80% of cases present with advanced stage disease. However, new treatments are emerging which offer hope to patients with advanced disease. Insights into cell biology have identified numerous intracellular and extracellular peptides that are pivotal in cancer cell signalling. Disrupting the function of these peptides inhibits intracellular signal transduction and diminishes uncontrolled proliferation, resistance to apoptosis and tumour angiogenesis. The most widely studied signalling pathway is the Epidermal Growth Factor (EGF) pathway. EGF signalling can be disrupted at numerous points. Blockade of the cell surface receptor is achieved by the monoclonal antibody cetuximab; intracellular tyrosine kinase activity is inhibited by erlotinib. Vascular Endothelial Growth Factor (VEGF) regulates another pathway important for tumour growth. Inhibition of VEGF impairs angiogenesis and disrupts metastatic spread. Bevacizumab is a monoclonal antibody that binds to VEGF and blocks interaction with its cell surface receptor. Clinical trials have demonstrated that disruption of these signalling pathways can improve survival in advanced lung cancer. New compounds including folate antimetabolites such as pemetrexed, proteasome inhibitors such as bortezomib, modified glutathione analogues such as TLK286, and other agents such as epothilones and other small molecules are currently being evaluated in patients with lung cancer. As more and more signalling peptides are targeted for manipulation, it is hoped that a new era is dawning in the treatment of advanced stage lung cancer. This review will focus on emerging new therapies in the management of lung cancer.

  7. Selective anti-cancer agents as anti-aging drugs.

    Science.gov (United States)

    Blagosklonny, Mikhail V

    2013-12-01

    Recent groundbreaking discoveries have revealed that IGF-1, Ras, MEK, AMPK, TSC1/2, FOXO, PI3K, mTOR, S6K, and NFκB are involved in the aging process. This is remarkable because the same signaling molecules, oncoproteins and tumor suppressors, are well-known targets for cancer therapy. Furthermore, anti-cancer drugs aimed at some of these targets have been already developed. This arsenal could be potentially employed for anti-aging interventions (given that similar signaling molecules are involved in both cancer and aging). In cancer, intrinsic and acquired resistance, tumor heterogeneity, adaptation, and genetic instability of cancer cells all hinder cancer-directed therapy. But for anti-aging applications, these hurdles are irrelevant. For example, since anti-aging interventions should be aimed at normal postmitotic cells, no selection for resistance is expected. At low doses, certain agents may decelerate aging and age-related diseases. Importantly, deceleration of aging can in turn postpone cancer, which is an age-related disease.

  8. Potential of radiosensitizing agents in cancer chemo-radiotherapy

    Directory of Open Access Journals (Sweden)

    Girdhani S

    2005-01-01

    Full Text Available Potential of herbs and other plant-based formulations have been increasingly recognized in prevention and treatment of human diseases including cancer. There exist enormous prospect for screening and evaluation of herbal/plant products for developing effective radiosensitization and radioprotection relevant to nuclear research program. Investigations in our laboratory have focused on the mechanism of activity of variety of anticancer and antioxidant agents, namely, Eugenol, (EU, Ellagic acid (EA, Triphala (TPL, Tocopherol Succinate (TOS and Arachidonic acid on normal and cancer cells with view to design effective protocols in practical radioprotection and cancer radiotherapy. This paper is mainly focused on studies on cytotoxic effects on cancer cell lines. Results have shown that these agents produced radiosensitizing action involving oxidative damage, membrane alteration and damage to nucleic acid in various human cell lines. Studies were performed employing fluorescence probes and electron spin resonance methods and gel electrophoresis protocols. It has been found that cytotoxic effect was induced by initiating membrane oxidative damage and by triggering intracellular generation of reactive oxygen species (ROS by gamma radiation in combination with phytochemicals like TPL, EA and TOS in tumor cell line Ehrlich Ascites (EAC, Human cervical (HeLa and breast (MCF-7 cells. Membrane damage and ROS generation was measured by DPH and DCF-FDA fluorescent probes respectively after exposure to low to moderate doses of gamma radiation. This talk will present the cytotoxic effects of phytochemicals in combination with ionizing radiation. It is emphasized that modulation of membrane peroxidative damage and intra cellular ROS may help achieve efficient killing of cancer cells which may provide a new approach to developing effective treatment of cancer.

  9. Chromone derivatives as antioxidant agents : the structural variable

    OpenAIRE

    Machado, Nelson Filipe Lopes

    2012-01-01

    Tese de doutoramento em Bioquímica (Biofísica Molecular) apresentada à Faculdade de Ciências e Tecnologia da Universidade de Coimbra Since oxidative stress is known to be the basis for numerous severe pathologies, from cardiovascular and neurodegenerative disorders to cancer, the development of effective antioxidant agents from natural origin has been the object of vigorous research in the last decade, in view of establishing novel chemopreventive strategies against these diseases...

  10. Lung cancer mutations and use of targeted agents in Hispanics.

    Science.gov (United States)

    Cress, W Douglas; Chiappori, Alberto; Santiago, Pedro; Muñoz-Antonia, Teresita

    2014-01-01

    Hispanic/Latinos (H/L) are expected to grow to over 24% of the USA population by 2050 and lung cancer is the number one cause of cancer death among H/L men. Due to the information that is becoming available via genetic testing, lung cancer molecular profiling is allowing for increasing application of personalized lung cancer therapies. However, to benefit the most people, development of these therapies and genetic tests must include research on as many racial and ethnic groups as possible. The purpose of this review is to bring attention to the fact that the mutations driving lung cancer in H/Ls differ in frequency and nature relative to the non-Hispanic White (WNH) majority that dominate current databases and participate in clinical trials that test new therapies. Clinical trials using new agents targeting genetic alterations (driver mutations) in lung cancer have demonstrated significant improvements in patient outcomes (for example, gefitinib, erlotinib or crizotinib for lung adenocarcinomas harboring EGFR mutations or EML4-ALK fusions, respectively). The nature and frequencies of some lung cancer driver mutations have been shown to be considerably different among racial and ethnic groups. This is particularly true for H/Ls. For example, several reports suggest a dramatic shift in the mutation pattern from predominantly KRAS in a WNH population to predominantly EGFR in multiple H/L populations. However, these studies are limited, and the effects of racial and ethnic differences on the incidence of mutations in lung cancer remain incompletely understood. This review serves as a call to address this problem.

  11. Mucoadhesive Fenretinide Patches for Site-specific Chemoprevention of Oral Cancer: Enhancement of Oral Mucosal Permeation of Fenretinide by Co-incorporation of Propylene Glycol and Menthol

    Science.gov (United States)

    Wu, Xiao; Desai, Kashappa-Goud H.; Mallery, Susan R.; Holpuch, Andrew S.; Phelps, Maynard P.; Schwendeman, Steven P.

    2012-01-01

    The objective of this study was to enhance oral mucosal permeation of fenretinide by co-incorporation of propylene glycol (PG) and menthol in fenretinide/Eudragit® RL PO mucoadhesive patches. Fenretinide is an extremely hydrophobic chemopreventive compound with poor tissue permeability. Co-incorporation of 5-10 wt% PG (mean Js = 16-23 μg cm−2 h−1; 158-171 μg fenretinide/g tissue) or 1-10 wt% PG + 5 wt% menthol (mean Js = 18-40 μg cm−2 h−1; 172-241 μg fenretinide/g tissue) in fenretinide/Eudragit® RL PO patches led to significant ex vivo fenretinide permeation enhancement (p < 0.001). Addition of PG above 2.5 wt% in the patch resulted in significant cellular swelling in the buccal mucosal tissues. These alterations were ameliorated by combining both enhancers and reducing PG level. After buccal administration of patches in rabbits, in vivo permeation of fenretinide across the oral mucosa was greater (~43 μg fenretinide/g tissue) from patches that contained optimized permeation enhancer content (2.5 wt% PG + 5 wt% menthol) relative to permeation obtained from enhancer-free patch (~ 17 μg fenretinide/g tissue) (p < 0.001). In vitro and in vivo release of fenretinide from patch was not significantly increased by co-incorporation of permeation enhancers, indicating that mass transfer across the tissue, and not the patch, largely determined the permeation rate control in vivo. As a result of its improved permeation and its lack of deleterious local effects, the mucoadhesive fenretinide patch co-incorporated with 2.5 wt% PG + 5 wt% menthol represents an important step in the further preclinical evaluation of oral site-specific chemoprevention strategies with fenretinide. PMID:22280430

  12. miR181b is induced by the chemopreventive polyphenol curcumin and inhibits breast cancer metastasis via down-regulation of the inflammatory cytokines CXCL1 and -2.

    Science.gov (United States)

    Kronski, Emanuel; Fiori, Micol E; Barbieri, Ottavia; Astigiano, Simonetta; Mirisola, Valentina; Killian, Peter H; Bruno, Antonino; Pagani, Arianna; Rovera, Francesca; Pfeffer, Ulrich; Sommerhoff, Christian P; Noonan, Douglas M; Nerlich, Andreas G; Fontana, Laura; Bachmeier, Beatrice E

    2014-05-01

    Chronic inflammation is a major risk factor for the development and metastatic progression of cancer. We have previously reported that the chemopreventive polyphenol Curcumin inhibits the expression of the proinflammatory cytokines CXCL1 and -2 leading to diminished formation of breast and prostate cancer metastases. In the present study, we have analyzed the effects of Curcumin on miRNA expression and its correlation to the anti-tumorigenic properties of this natural occurring polyphenol. Using microarray miRNA expression analyses, we show here that Curcumin modulates the expression of a series of miRNAs, including miR181b, in metastatic breast cancer cells. Interestingly, we found that miR181b down-modulates CXCL1 and -2 through a direct binding to their 3'-UTR. Overexpression or inhibition of miR181b in metastatic breast cancer cells has a significant impact on CXCL1 and -2 and is required for the effect of Curcumin on these two cytokines. miR181b also mediates the effects of Curcumin on inhibition of proliferation and invasion as well as induction of apoptosis. Importantly, over-expression of miR181b in metastatic breast cancer cells inhibits metastasis formation in vivo in immunodeficient mice. Finally, we demonstrated that Curcumin up-regulates miR181b and down-regulates CXCL1 and -2 in cells isolated from several primary human breast cancers. Taken together, these data show that Curcumin provides a simple bridge to bring metastamir modulation into the clinic, placing it in a primary and tertiary preventive, as well as a therapeutic, setting. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  13. Antibody-Based Cancer Therapy: Successful Agents and Novel Approaches.

    Science.gov (United States)

    Hendriks, D; Choi, G; de Bruyn, M; Wiersma, V R; Bremer, E

    2017-01-01

    Since their discovery, antibodies have been viewed as ideal candidates or "magic bullets" for use in targeted therapy in the fields of cancer, autoimmunity, and chronic inflammatory disorders. A wave of antibody-dedicated research followed, which resulted in the clinical approval of a first generation of monoclonal antibodies for cancer therapy such as rituximab (1997) and cetuximab (2004), and infliximab (2002) for the treatment of autoimmune diseases. More recently, the development of antibodies that prevent checkpoint-mediated inhibition of T cell responses invigorated the field of cancer immunotherapy. Such antibodies induced unprecedented long-term remissions in patients with advanced stage malignancies, most notably melanoma and lung cancer, that do not respond to conventional therapies. In this review, we will recapitulate the development of antibody-based therapy, and detail recent advances and new functions, particularly in the field of cancer immunotherapy. With the advent of recombinant DNA engineering, a number of rationally designed molecular formats of antibodies and antibody-derived agents have become available, and we will discuss various molecular formats including antibodies with improved effector functions, bispecific antibodies, antibody-drug conjugates, antibody-cytokine fusion proteins, and T cells genetically modified with chimeric antigen receptors. With these exciting advances, new antibody-based treatment options will likely enter clinical practice and pave the way toward more successful control of malignant diseases. © 2017 Elsevier Inc. All rights reserved.

  14. Neem Limonoids as Anticancer Agents: Modulation of Cancer Hallmarks and Oncogenic Signaling.

    Science.gov (United States)

    Nagini, Siddavaram

    2014-01-01

    Neem (Azadirachta indica A. Juss) is one of the most versatile medicinal plants, widely distributed in the Indian subcontinent. Neem is a rich source of limonoids that are endowed with potent medicinal properties predominantly antioxidant, anti-inflammatory, and anticancer activities. Azadirachtin, gedunin, and nimbolide are more extensively investigated relative to other neem limonoids. Accumulating evidence indicates that the anticancer effects of neem limonoids are mediated through the inhibition of hallmark capabilities of cancer such as cell proliferation, apoptosis evasion, inflammation, invasion, and angiogenesis. The neem limonoids have been demonstrated to target oncogenic signaling kinases and transcription factors chiefly, NF-κB, Wnt/β-catenin, PI3K/Akt, MAPK, and JAK/STAT signaling pathways. Neem limonoids that target multiple pathways that are aberrant in cancer are ideal candidates for cancer chemoprevention and therapy. © 2014 Elsevier Inc. All rights reserved.

  15. Potential chemopreventive activity of a new macrolide antibiotic from a marine-derived Micromonospora sp.

    Science.gov (United States)

    Carlson, Skylar; Marler, Laura; Nam, Sang-Jip; Santarsiero, Bernard D; Pezzuto, John M; Murphy, Brian T

    2013-04-03

    Agents capable of inducing phase II enzymes such as quinone reductase 1 (QR1) are known to have the potential of mediating cancer chemopreventive activity. As part of a program to discover novel phase II enzyme-inducing molecules, we identified a marine-derived actinomycete strain (CNJ-878) that exhibited activity with cultured Hepa 1c1c7 cells. Based on this activity, a new macrolide, juvenimicin C (1), as well as 5-O-α-L-rhamnosyltylactone (2), were isolated from the culture broth of a Micromonospora sp. Compound 1 enhanced QR1 enzyme activity and glutathione levels by two-fold with CD values of 10.1 and 27.7 μM, respectively. In addition, glutathione reductase and glutathione peroxidase activities were elevated. This is the first reported member of the macrolide class of antibiotics found to mediate these responses.

  16. Chemopreventive and antioxidant activity of 6-substituted imidazo[2,1-b]thiazoles.

    Science.gov (United States)

    Andreani, Aldo; Leoni, Alberto; Locatelli, Alessandra; Morigi, Rita; Rambaldi, Mirella; Cervellati, Rinaldo; Greco, Emanuela; Kondratyuk, Tamara P; Park, Eun-Jung; Huang, Ke; van Breemen, Richard B; Pezzuto, John M

    2013-10-01

    The synthesis of new imidazo[2,1-b]thiazoles bearing phenolic groups is reported. These compounds and some previously described analogs were evaluated as antioxidant agents with three chemical model systems, and cancer chemopreventive potential was examined by inhibition of NO production, TNF-α activated NFκB activity, and aromatase activity, as well as induction of QR1 and RXRE binding. Two of the test compounds, 9 and 12, displayed promising activity by inhibiting iNOS, NFκB and aromatase in dose-dependent manner, with IC50 values in low micromolar range. The same compounds activated QR1 in a bifunctional manner. When incubated with human liver microsomes, the active compounds were further hydroxylated on the parent ring system, suggesting the next logical step in the development of these promising leads will entail synthetic production of metabolites followed by additional assessment of biological activity. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  17. Potential Chemopreventive Activity of a New Macrolide Antibiotic from a Marine-Derived Micromonospora sp.

    Directory of Open Access Journals (Sweden)

    Brian T. Murphy

    2013-04-01

    Full Text Available Agents capable of inducing phase II enzymes such as quinone reductase 1 (QR1 are known to have the potential of mediating cancer chemopreventive activity. As part of a program to discover novel phase II enzyme-inducing molecules, we identified a marine-derived actinomycete strain (CNJ-878 that exhibited activity with cultured Hepa 1c1c7 cells. Based on this activity, a new macrolide, juvenimicin C (1, as well as 5-O-α-l-rhamnosyltylactone (2, were isolated from the culture broth of a Micromonospora sp. Compound 1 enhanced QR1 enzyme activity and glutathione levels by two-fold with CD values of 10.1 and 27.7 μM, respectively. In addition, glutathione reductase and glutathione peroxidase activities were elevated. This is the first reported member of the macrolide class of antibiotics found to mediate these responses.

  18. Naturally occurring anti-cancer agents targeting EZH2.

    Science.gov (United States)

    Shahabipour, Fahimeh; Caraglia, Michele; Majeed, Muhammed; Derosa, Giuseppe; Maffioli, Pamela; Sahebkar, Amirhossein

    2017-08-01

    Natural products are considered as promising tools for the prevention and treatment of cancer. The enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase unit of polycomb repressor complexes such as PRC2 complex that has oncogenic roles through interference with growth and metastatic potential. Several agents targeting EZH2 has been discovered but they often induce side effects in clinical trials. Recently, EZH2 has emerged as a potential target of natural products with documented anti-cancer effects and this discloses a new scenario for the development of EZH2 inhibitory strategies with agents with low cytotoxic detrimental effects. In fact, several natural products such as curcumin, triptolide, ursolic acid, sulforaphane, davidiin, tanshindiols, gambogic acid, berberine and Alcea rosea have been shown to serve as EZH2 modulators. Mechanisms like inhibition of histone H3K4, H3K27 and H3K36 trimethylation, down-regulation of matrix metalloproteinase expression, competitive binding to the S-adenosylmethionine binding site of EZH2 and modulation of tumor-suppressive microRNAs have been demonstrated to mediate the EZH2-inhibitory activity of the mentioned natural products. This review summarizes the pathways that are regulated by various natural products resulting in the suppression of EZH2, and provides a plausible molecular mechanism for the putative anti-cancer effects of these compounds. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Nutrition Frontiers - Spring 2016 | Division of Cancer Prevention

    Science.gov (United States)

    Volume 7, Issue 2 The spring issue of Nutrition Frontiers showcases green tea's effect on human metabolism, fish oil — as a chemopreventive agent in myeloid leukemia and, with pectin, how they affect microRNA expression in the colon. Learn about our spotlight investigator, Dr. Richard Eckert, and his research on skin cancer prevention, upcoming announcements and more. |

  20. Topical Treatment with Diclofenac, Calcipotriol (Vitamin-D3 Analog) and Difluoromethylornithine (DFMO) Does Not Prevent Nonmelanoma Skin Cancer in Mice

    DEFF Research Database (Denmark)

    Pommergaard, H C; Burcharth, J; Rosenberg, J

    2013-01-01

    Nonmelanoma skin cancer is a common cancer type with increasing incidence. The purpose of this study was to evaluate topical application of diclofenac, calcipotriol, and difluoromethylornithine as chemoprevention in a mouse model of ultraviolet light-induced skin tumors, since these agents have b...

  1. Biological activities of fusarochromanone: a potent anti-cancer agent.

    Science.gov (United States)

    Mahdavian, Elahe; Palyok, Phillip; Adelmund, Steven; Williams-Hart, Tara; Furmanski, Brian D; Kim, Yoon-Jee; Gu, Ying; Barzegar, Mansoureh; Wu, Yang; Bhinge, Kaustubh N; Kolluru, Gopi K; Quick, Quincy; Liu, Yong-Yu; Kevil, Christopher G; Salvatore, Brian A; Huang, Shile; Clifford, John L

    2014-09-03

    Fusarochromanone (FC101) is a small molecule fungal metabolite with a host of interesting biological functions, including very potent anti-angiogenic and direct anti-cancer activity. Herein, we report that FC101 exhibits very potent in-vitro growth inhibitory effects (IC50 ranging from 10nM-2.5 μM) against HaCat (pre-malignant skin), P9-WT (malignant skin), MCF-7 (low malignant breast), MDA-231 (malignant breast), SV-HUC (premalignant bladder), UM-UC14 (malignant bladder), and PC3 (malignant prostate) in a time-course and dose-dependent manner, with the UM-UC14 cells being the most sensitive. FC101 induces apoptosis and an increase in proportion of cells in the sub-G1 phase in both HaCat and P9-WT cell lines as evidenced by cell cycle profile analysis. In a mouse xenograft SCC tumor model, FC101 was well tolerated, non-toxic, and achieved a 30% reduction in tumor size at a dose of 8 mg/kg/day. FC101 is also a potent anti-angiogenenic agent. At nanomolar doses, FC101 inhibits the vascular endothelial growth factor-A (VEGF-A)-mediated proliferation of endothelial cells. Our data presented here indicates that FC101 is an excellent lead candidate for a small molecule anti-cancer agent that simultaneously affects angiogenesis signaling, cancer signal transduction, and apoptosis. Further understanding of the underlying FC101's molecular mechanism may lead to the design of novel targeted and selective therapeutics, both of which are pursued targets in cancer drug discovery.

  2. The Chemopreventive Effect of Tanacetum Polycephalum Against LA7-Induced Breast Cancer in Rats and the Apoptotic Effect of a Cytotoxic Sesquiterpene Lactone in MCF7 Cells: A Bioassay-Guided Approach

    Directory of Open Access Journals (Sweden)

    Hamed Karimian

    2015-06-01

    Full Text Available Background: Tanacetum polycephalum L. Schultz-Bip is a member of the Asteraceae family. This study evaluated the chemopreventive effect of a T. polycephalum hexane extract (TPHE using in in vivo and in vitro models. Methods and Results: Five groups of rats: normal control, cancer control, TPHE low dose, TPHE high dose and positive control (tamoxifen were used for the in vivo study. Histopathological examination showed that TPHE significantly suppressed the carcinogenic effect of LA7 tumour cells. The tumour sections from TPHE-treated rats demonstrated significantly reduced expression of Ki67 and PCNA compared to the cancer control group. Using a bioassay-guided approach, the cytotoxic compound of TPHE was identified as a tricyclic sesquiterpene lactone, namely, 8β- hydroxyl- 4β, 15- dihydrozaluzanin C (HDZC. Signs of early and late apoptosis were observed in MCF7 cells treated with HDZC and were attributed to the mitochondrial intrinsic pathway based on the up-regulation of Bax and the down-regulation of Bcl-2. HDZC induced cell cycle arrest in MCF7 cells and increased the expression of p21 and p27 at the mRNA and protein levels. Conclusion: This results of this study substantiate the anticancer effect of TPHE and highlight the involvement of HDZC as one of the contributing compounds that act by initiating mitochondrial-mediated apoptosis.

  3. The Chemopreventive Effect of Tanacetum Polycephalum Against LA7-Induced Breast Cancer in Rats and the Apoptotic Effect of a Cytotoxic Sesquiterpene Lactone in MCF7 Cells: A Bioassay-Guided Approach.

    Science.gov (United States)

    Karimian, Hamed; Fadaeinasab, Mehran; Moghadamtousi, Soheil Zorofchian; Hajrezaei, Maryam; Zahedifard, Maryam; Razavi, Mahboubeh; Safi, Sher Zaman; Mohan, Syam; Khalifa, Shaden A M; El-Seedi, Hesham R; Abdulla, Mahmood Amin; Ali, Hapipah Mohd; Noordin, Mohamad Ibrahim

    2015-01-01

    Tanacetum polycephalum L. Schultz-Bip is a member of the Asteraceae family. This study evaluated the chemopreventive effect of a T. polycephalum hexane extract (TPHE) using in in vivo and in vitro models. Five groups of rats: normal control, cancer control, TPHE low dose, TPHE high dose and positive control (tamoxifen) were used for the in vivo study. Histopathological examination showed that TPHE significantly suppressed the carcinogenic effect of LA7 tumour cells. The tumour sections from TPHE-treated rats demonstrated significantly reduced expression of Ki67 and PCNA compared to the cancer control group. Using a bioassay-guided approach, the cytotoxic compound of TPHE was identified as a tricyclic sesquiterpene lactone, namely, 8β- hydroxyl- 4β, 15- dihydrozaluzanin C (HDZC). Signs of early and late apoptosis were observed in MCF7 cells treated with HDZC and were attributed to the mitochondrial intrinsic pathway based on the up-regulation of Bax and the down-regulation of Bcl-2. HDZC induced cell cycle arrest in MCF7 cells and increased the expression of p21 and p27 at the mRNA and protein levels. This results of this study substantiate the anticancer effect of TPHE and highlight the involvement of HDZC as one of the contributing compounds that act by initiating mitochondrial-mediated apoptosis. © 2015 S. Karger AG, Basel.

  4. Dietary Bioactive Diallyl Trisulfide in Cancer Prevention and Treatment

    Directory of Open Access Journals (Sweden)

    Michael T. Puccinelli

    2017-07-01

    Full Text Available Bioactive dietary agents have been shown to regulate multiple cancer hallmark pathways. Epidemiologic studies have linked consumption of Allium vegetables, such as garlic and onions, to decreased incidence of cancer. Diallyl trisulfide (DATS, a bioactive compound derived from Allium vegetables, has been investigated as an anti-cancer and chemopreventive agent. Preclinical studies provide ample evidence that DATS regulates multiple cancer hallmark pathways including cell cycle, apoptosis, angiogenesis, invasion, and metastasis. DATS has been shown to arrest cancer cells at multiple stages of the cell cycle with the G2/M arrest being the most widely reported. Additionally, increased pro-apoptotic capacity as a result of regulating intrinsic and extrinsic apoptotic pathway components has been widely reported following DATS treatment. Invasion, migration, and angiogenesis represent emerging targets of DATS and support its anti-cancer properties. This review summarizes DATS mechanisms of action as an anti-cancer and chemopreventive agent. These studies provide rationale for future investigation into its use as a cancer chemopreventive agent.

  5. Pharmacogenomics of Targeted Agents for Personalization of Colorectal Cancer Treatment.

    Science.gov (United States)

    Bignucolo, Alessia; De Mattia, Elena; Cecchin, Erika; Roncato, Rossana; Toffoli, Giuseppe

    2017-07-14

    The use of targeted agents in the treatment of metastatic colorectal cancer (CRC) has improved patient outcomes. Anti-epidermal growth factor receptor (anti-EGFR) agents (cetuximab and panitumumab) and antiangiogenic molecules (bevacizumab, regorafeninb, ramucirumab, and aflibercept) have been successfully integrated into clinical practice. Other drugs have been designed to target additional deregulated pathways in CRC, such as MAPK (mitogen-activated protein kinase)/PI3K-AKT (phosphatidylinositol-3-kinase-AKT serine/threonine kinase)/mTOR (mammalian target of rapamycin), HER-2 and 3 ( human epidermal growth factor receptor-2 and -3), and BRAF. A major issue with targeted treatment is early identification of patients with primary or secondary drug resistance. Pharmacogenomic research has demonstrated its value in this field, highlighting some tumor mutations that could discriminate responders from non-responders. The tumor genetic profile of the RAS/RAF pathway is needed before treatment with anti-EGFR agents; mutations in EGFR pathway genes have also been explored in relation to antiangiogenic molecules although further data are required prior to their integration into clinical practice. The introduction of immunotherapy has paved the way for a new generation of predictive markers, including genome-wide assessment of the tumor landscape. Furthermore, the development of next generation sequencing technology and non-invasive approaches to analyze circulating tumor DNA will make real-time monitoring of the tumor pharmacogenomic markers possible in the clinical routine, rendering precision medicine available to every patient.

  6. Understanding the molecular mechanisms of cancer prevention by dietary phytochemicals: From experimental models to clinical trials.

    Science.gov (United States)

    Maru, Girish B; Hudlikar, Rasika R; Kumar, Gaurav; Gandhi, Khushboo; Mahimkar, Manoj B

    2016-02-26

    Chemoprevention is one of the cancer prevention approaches wherein natural/synthetic agent(s) are prescribed with the aim to delay or disrupt multiple pathways and processes involved at multiple steps, i.e., initiation, promotion, and progression of cancer. Amongst environmental chemopreventive compounds, diet/beverage-derived components are under evaluation, because of their long history of exposure to humans, high tolerability, low toxicity, and reported biological activities. This compilation briefly covers and compares the available evidence on chemopreventive efficacy and probable mechanism of chemoprevention by selected dietary phytochemicals (capsaicin, curcumin, diallyl sulphide, genistein, green/black tea polyphenols, indoles, lycopene, phenethyl isocyanate, resveratrol, retinoids and tocopherols) in experimental systems and clinical trials. All the dietary phytochemicals covered in this review have demonstrated chemopreventive efficacy against spontaneous or carcinogen-induced experimental tumors and/or associated biomarkers and processes in rodents at several organ sites. The observed anti-initiating, anti-promoting and anti-progression activity of dietary phytochemicals in carcinogen-induced experimental models involve phytochemical-mediated redox changes, modulation of enzymes and signaling kinases resulting to effects on multiple genes and cell signaling pathways. Results from clinical trials using these compounds have not shown them to be chemopreventive. This may be due to our: (1) inability to reproduce the exposure conditions, i.e., levels, complexity, other host and lifestyle factors; and (2) lack of understanding about the mechanisms of action and agent-mediated toxicity in several organs and physiological processes in the host. Current research efforts in addressing the issues of exposure conditions, bioavailability, toxicity and the mode of action of dietary phytochemicals may help address the reason for observed mismatch that may ultimately

  7. Lymphohematopoietic Cancers Induced by Chemicals and Other Agents: Overview and Implications for Risk Assessment (Final Report)

    Science.gov (United States)

    EPA announced the release of the final report, Lymphohematopoietic Cancers Induced by Chemicals and Other Agents: Overview and Implications for Risk Assessment . This report provides an overview of the types of mechanisms underlying the lymphohematopoietic cancers induc...

  8. DNA damage and aberrant crypt foci as putative biomarkers to evaluate the chemopreventive effect of annatto (Bixa orellana L.) in rat colon carcinogenesis.

    Science.gov (United States)

    Agner, Aniele R; Bazo, Ana P; Ribeiro, Lúcia R; Salvadori, Daisy M F

    2005-04-04

    Chemoprevention opens new perspectives in the prevention of cancer and other degenerative diseases. Use of target-organ biological models at the histological and genetic levels can markedly facilitate the identification of such potential chemopreventive agents. Colon cancer is one of the highest incidence rates throughout the world and some evidences have indicated carotenoids as possible agents that decrease the risk of colorectal cancer. In the present study, we evaluate the activity of annatto (Bixa orellana L.), a natural food colorant rich in carotenoid, on the formation of aberrant crypt foci (ACF) induced by dimethylhydrazine (DMH) in rat colon. Further, we investigate, the effect of annatto on DMH-induced DNA damage, by the comet assay. Male Wistar rats were given s.c. injections of DMH (40 mg/kg body wt.) twice a week for 2 weeks to induce ACF. They also received experimental diets containing annatto at 20, 200 or 1000 ppm for five 5 weeks before (pre-treatment), or 10 weeks after (post-treatment) DMH treatment. In both protocols the rats were sacrificed on week 15th. For the comet assay, the animals were fed with the same experimental diets for 2 weeks. Four hours before the sacrifice, the animals received an s.c. injection of DMH (40 mg/kg body wt.). Under such conditions, dietary administration of 1000 ppm annatto neither induce DNA damage in blood and colon cells nor aberrant crypt foci in rat distal colon. Conversely, annatto was successful in inhibiting the number of crypts/colon (animal), but not in the incidence of DMH-induced ACF, mainly when administered after DMH. However, no antigenotoxic effect was observed in colon cells. These findings suggest possible chemopreventive effects of annatto through their modulation of the cryptal cell proliferation but not at the initiation stage of colon carcinogenesis.

  9. Risk factors and chemoprevention in Barrett's esophagus--an update.

    Science.gov (United States)

    Winberg, Hanna; Lindblad, Mats; Lagergren, Jesper; Dahlstrand, Hanna

    2012-04-01

    Barrett's esophagus (BO) is a precursor of esophageal adenocarcinoma (OAC), a cancer with a poor prognosis and an increasing incidence. Hence there is an interest in mapping causal factors underlying BO and finding strategies to reduce the risk of dysplasia progression in patients with BO. Here we review current knowledge on established as well as less risk factors for the development of BO. Additionally, we summarize today's status on the use of chemoprevention aiming to reduce the risk of cancer progression in BO patients. We searched Medline and the Cochrane Library using the MeSH terms "Barrett's esophagus" and "Barrett esophagus," both alone and combined with the terms "risk factor," "aetiology," "diet," or "prevention." Focus was on original contributions, systematic reviews, and meta-analyses. Established risk factors for the development of BO include gastro-esophageal reflux, obesity, male gender, Caucasian ethnicity, and increasing age. Smoking might increase the risk of BO, while aspirin/NSAIDs, Helicobacter pylori infection, and specific "healthy" dietary factors may lower the risk. The potential value of using chemoprevention with proton pump inhibitors, aspirin/NSAIDs, or statins is still uncertain. There is today a substantial knowledge of risk factors of BO. Certain diet may be protective of BO, albeit yet to be proven. The efficiency of chemoprevention in BO is currently addressed further in randomized clinical trials.

  10. T-oligo as an anticancer agent in colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wojdyla, Luke; Stone, Amanda L. [Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, IL (United States); Sethakorn, Nan [Department of Medicine, University of Chicago, Chicago, IL (United States); Uppada, Srijayaprakash B.; Devito, Joseph T. [Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, IL (United States); Bissonnette, Marc [Department of Medicine, University of Chicago, Chicago, IL (United States); Puri, Neelu, E-mail: neelupur@uic.edu [Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, IL (United States)

    2014-04-04

    Highlights: • T-oligo induces cell cycle arrest, senescence, apoptosis, and differentiation in CRC. • Treatment with T-oligo downregulates telomere-associated proteins. • T-oligo combined with an EGFR-TKI additively inhibits cellular proliferation. • T-oligo has potential as an effective therapeutic agent for CRC. - Abstract: In the United States, there will be an estimated 96,830 new cases of colorectal cancer (CRC) and 50,310 deaths in 2014. CRC is often detected at late stages of the disease, at which point there is no effective chemotherapy. Thus, there is an urgent need for effective novel therapies that have minimal effects on normal cells. T-oligo, an oligonucleotide homologous to the 3′-telomere overhang, induces potent DNA damage responses in multiple malignant cell types, however, its efficacy in CRC has not been studied. This is the first investigation demonstrating T-oligo-induced anticancer effects in two CRC cell lines, HT-29 and LoVo, which are highly resistant to conventional chemotherapies. In this investigation, we show that T-oligo may mediate its DNA damage responses through the p53/p73 pathway, thereby inhibiting cellular proliferation and inducing apoptosis or senescence. Additionally, upregulation of downstream DNA damage response proteins, including E2F1, p53 or p73, was observed. In LoVo cells, T-oligo induced senescence, decreased clonogenicity, and increased expression of senescence associated proteins p21, p27, and p53. In addition, downregulation of POT1 and TRF2, two components of the shelterin protein complex which protects telomeric ends, was observed. Moreover, we studied the antiproliferative effects of T-oligo in combination with an EGFR tyrosine kinase inhibitor, Gefitinib, which resulted in an additive inhibitory effect on cellular proliferation. Collectively, these data provide evidence that T-oligo alone, or in combination with other molecularly targeted therapies, has potential as an anti-cancer agent in CRC.

  11. An epidemiologic risk prediction model for ovarian cancer in Europe : The EPIC study

    NARCIS (Netherlands)

    Li, K.; Huesing, A.; Fortner, R. T.; Tjonneland, A.; Hansen, L.; Dossus, L.; Chang-Claude, J.; Bergmann, M.; Steffen, A.; Bamia, C.; Trichopoulos, D.; Trichopoulou, A.; Palli, D.; Mattiello, A.; Agnoli, C.; Tumino, R.; Onland-Moret, N. C.; Peeters, P. H.; Bueno-de-Mesquita, H. B(as); Gram, I. T.; Weiderpass, E.; Sanchez-Cantalejo, E.; Chirlaque, M-D; Duell, E. J.; Ardanaz, E.; Idahl, A.; Lundin, E.; Khaw, K-T; Travis, R. C.; Merritt, M. A.; Gunter, M. J.; Riboli, E.; Ferrari, P.; Terry, K.; Cramer, D.; Kaaks, R.

    2015-01-01

    Background: Ovarian cancer has a high case-fatality ratio, largely due to late diagnosis. Epidemiologic risk prediction models could help identify women at increased risk who may benefit from targeted prevention measures, such as screening or chemopreventive agents. Methods: We built an ovarian

  12. Inhibition of akt enhances the chemopreventive effects of topical rapamycin in mouse skin

    Science.gov (United States)

    Dickinson, Sally E; Janda, Jaroslav; Criswell, Jane; Blohm-Mangone, Karen; Olson, Erik R.; Liu, Zhonglin; Barber, Christie; Rusche, Jadrian J.; Petricoin, Emmanuel; Calvert, Valerie; Einspahr, Janine G.; Dickinson, Jesse; Stratton, Steven P.; Curiel-Lewandrowski, Clara; Saboda, Kathylynn; Hu, Chengcheng; Bode, Ann M.; Dong, Zigang; Alberts, David S.; Bowden, G. Timothy

    2016-01-01

    The PI3Kinase/Akt/mTOR pathway has important roles in cancer development for multiple tumor types, including UV-induced non-melanoma skin cancer. Immunosuppressed populations are at increased risk of aggressive cutaneous squamous cell carcinoma (SCC). Individuals who are treated with rapamycin, (sirolimus, a classical mTOR inhibitor) have significantly decreased rates of developing new cutaneous SCCs compared to those that receive traditional immunosuppression. However, systemic rapamycin use can lead to significant adverse events. Here we explored the use of topical rapamycin as a chemopreventive agent in the context of solar simulated light (SSL)-induced skin carcinogenesis. In SKH-1 mice, topical rapamycin treatment decreased tumor yields when applied after completion of 15 weeks of SSL exposure compared to controls. However, applying rapamycin during SSL exposure for 15 weeks, and continuing for 10 weeks after UV treatment, increased tumor yields. We also examined whether a combinatorial approach might result in more significant tumor suppression by rapamycin. We validated that rapamycin causes increased Akt (S473) phosphorylation in the epidermis after SSL, and show for the first time that this dysregulation can be inhibited in vivo by a selective PDK1/Akt inhibitor, PHT-427. Combining rapamycin with PHT-427 on tumor prone skin additively caused a significant reduction of tumor multiplicity compared to vehicle controls. Our findings indicate that patients taking rapamycin should avoid sun exposure, and that combining topical mTOR inhibitors and Akt inhibitors may be a viable chemoprevention option for individuals at high risk for cutaneous SCC.

  13. Glucose-lowering agents and the patterns of risk for cancer

    DEFF Research Database (Denmark)

    van Staa, T P; Patel, D; Gallagher, A M

    2012-01-01

    .77 [95% CI 0.56, 1.07] and 0.60 [95% CI 0.36, 1.02], respectively, for 6-24, 25-60 and >60 months). CONCLUSIONS: These findings do not provide evidence of either beneficial or adverse effects of glucose-lowering agents on cancer risk and are consistent with changes in diabetes treatment in the few months......INTRODUCTION: Recent studies suggesting an increased cancer risk with glucose-lowering agents have received widespread publicity. The objectives of this study were to evaluate the comparability in underlying cancer risk and patterns of cancer risk over time with different glucose-lowering agents....... METHODS: The General Practice Research Database (GPRD) was used to identify cohorts of new users. Cancer outcomes were obtained from the GPRD, Hospital Episode Statistics and cancer registries. Relative rates of cancer comparing different glucose-lowering agents were estimated using Poisson regression...

  14. Chemopreventive activity of methanol extract of Melastoma ...

    African Journals Online (AJOL)

    Chemopreventive activity of methanol extract of Melastoma malabathricum leaves in DMBA-induced mouse skin carcinogenesis. ... Conclusion: MEMM demonstrated chemoprevention possibly via its antioxidant and anti-inflammatory activities, and the action of flavonoids like quercitrin. Key words: Melastomaceae; skin ...

  15. Chemopreventive efficacy of hesperidin against chemically induced nephrotoxicity and renal carcinogenesis via amelioration of oxidative stress and modulation of multiple molecular pathways.

    Science.gov (United States)

    Siddiqi, Aisha; Hasan, Syed Kazim; Nafees, Sana; Rashid, Summya; Saidullah, Bano; Sultana, Sarwat

    2015-12-01

    In the present study, chemopreventive efficacy of hesperidin was evaluated against ferric nitrilotriacetate (Fe-NTA) induced renal oxidative stress and carcinogenesis in wistar rats. Nephrotoxicity was induced by single intraperitoneal injection of Fe-NTA (9 mg Fe/kg b.wt). Renal cancer was initiated by the administration of N-nitrosodiethylamine (DEN 200mg/kg b.wt ip) and promoted by Fe-NTA (9 mg Fe/kg b.wt ip) twice weekly for 16 weeks. Efficacy of hesperidin against Fe-NTA-induced nephrotoxicity was assessed in terms of biochemical estimation of antioxidant enzyme activities viz. reduced renal GSH, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, catalase, superoxide dismutase and renal toxicity markers (BUN, Creatinine, KIM-1). Administration of Fe-NTA significantly depleted antioxidant renal armory, enhanced renal lipid peroxidation as well as the levels of BUN, creatinine and KIM-1. However, simultaneous pretreatment of hesperidin restored their levels in a dose dependent manner. Expression of apoptotic markers caspase-3, caspase-9, bax, bcl-2 and proliferative marker PCNA along with inflammatory markers (NFκB, iNOS, TNF-α) were also analysed to assess the chemopreventive potential of hesperidin in two-stage renal carcinogenesis model. Hesperidin was found to induce caspase-3, caspase-9, bax expression and downregulate bcl-2, NFκB, iNOS, TNF-α, PCNA expression. Histopathological findings further revealed hesperidin's chemopreventive efficacy by restoring the renal morphology. Our results provide a powerful evidence suggesting hesperidin to be a potent chemopreventive agent against renal carcinogenesis possibly by virtue of its antioxidant properties and by modulation of multiple molecular pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid has enhanced chemo-preventive properties compared to aspirin, is gastrointestinal safe with all the classic therapeutic indications

    Science.gov (United States)

    Kodela, Ravinder; Chattopadhyay, Mitali; Velázquez-Martínez, Carlos A.; Kashfi, Khosrow

    2015-01-01

    Aspirin is chemopreventive; however, side effects preclude its long-term use. NOSH-aspirin (NBS-1120), a novel hybrid that releases nitric oxide and hydrogen sulfide, was designed to be a safer alternative. Here we compare the gastrointestinal safety, anti-inflammatory, analgesic, antipyretic, anti-platelet, and chemopreventive properties of aspirin and NBS-1120 administered orally to rats at equimolar doses. Gastrointestinal safety: 6h post-administration, the number and size of hemorrhagic lesions in stomachs were counted; tissue samples were frozen for PGE2, SOD, and MDA determination. Anti-inflammatory: 1h after drug administration, the volume of carrageenan-induced rat paw edemas was measured for 5h. Anti-pyretic: fever was induced by LPS (ip) an hour before administration of the test drugs, core body temperature was measured hourly for 5h. Analgesic: time-dependent analgesic effects were evaluated by carrageenan-induced hyperalgesia. Antiplatelet: anti-aggregatory effects were studied on collagen-induced platelet aggregation of human platelet-rich plasma. Chemoprevention: Nude mice were gavaged daily for 25 days with vehicle, aspirin or NBS-1120. After one week, each mouse was inoculated subcutaneously in the right flank with HT-29 human colon cancer cells. Both agents reduced PGE2 levels in stomach tissue; however, NBS-1120 did not cause any stomach ulcers, whereas aspirin caused significant bleeding. Lipid peroxidation induced by aspirin was higher than that exerted by NBS-1120. SOD activity was significantly inhibited by aspirin but increased by NBS-1120. Both agents showed similar anti-inflammatory, analgesic, anti-pyretic, and anti-platelet activities. Aspirin increased plasma TNFα more than NBS-1120-treated animals. NBS-1120 was better than aspirin as a chemopreventive agent; it dose-dependently inhibited tumor growth and tumor mass. PMID:26394025

  17. Effects of n-3 PUFAs on breast cancer cells through their incorporation in plasma membrane

    OpenAIRE

    Corsetto, Paola A; Montorfano, Gigliola; Zava, Stefania; Jovenitti, Ilaria E; Cremona, Andrea; Berra, Bruno; Rizzo, Angela M

    2011-01-01

    Abstract Background PUFAs are important molecules for membrane order and function; they can modify inflammation-inducible cytokines production, eicosanoid production, plasma triacylglycerol synthesis and gene expression. Recent studies suggest that n-3 PUFAs can be cancer chemopreventive, chemosuppressive and auxiliary agents for cancer therapy. N-3 PUFAs could alter cancer growth influencing cell replication, cell cycle, and cell death. The question that remains to be answered is how n-3 PUF...

  18. Single Walled Carbon Nanohorns as Photothermal Cancer Agents

    Energy Technology Data Exchange (ETDEWEB)

    Whitney, John [Virginia Polytechnic Institute and State University (Virginia Tech); Sarkar, Saugata [Virginia Polytechnic Institute and State University (Virginia Tech); Zhang, Jianfei [Virginia Polytechnic Institute and State University (Virginia Tech); Do, Thao [Virginia Polytechnic Institute and State University (Virginia Tech); Manson, Mary kyle [Virginia Polytechnic Institute and State University (Virginia Tech); Campbell, Tom [Virginia Polytechnic Institute and State University (Virginia Tech); Puretzky, Alexander A [ORNL; Rouleau, Christopher M [ORNL; More, Karren Leslie [ORNL; Geohegan, David B [ORNL; Rylander, Christopher [Virginia Polytechnic Institute and State University (Virginia Tech); Dorn, Harry C [Virginia Polytechnic Institute and State University (Virginia Tech); Rylander, Nichole M [Virginia Polytechnic Institute and State University (Virginia Tech)

    2011-01-01

    Nanoparticles have significant potential as selective photo-absorbing agents for laser based cancer treatment. This study investigates the use of single walled carbon nanohorns (SWNHs) as thermal enhancers when excited by near infrared (NIR) light for tumor cell destruction. Absorption spectra of SWNHs in deionized water at concentrations of 0, 0.01, 0.025, 0.05, 0.085, and 0.1 mg/ml were measured using a spectrophotometer for the wavelength range of 200-1,400 nm. Mass attenuation coefficients were calculated using spectrophotometer transmittance data. Cell culture media containing 0, 0.01, 0.085, and 0.333 mg/ml SWNHs was laser irradiated at 1,064 nm wavelength with an irradiance of 40 W/cm{sup 2} for 0-5 minutes. Temperature elevations of these solutions during laser irradiation were measured with a thermocouple 8 mm away from the incident laser beam. Cell viability of murine kidney cancer cells (RENCA) was measured 24 hours following laser treatment with the previously mentioned laser parameters alone or with SWNHs. Cell viability as a function of radial position was determined qualitatively using trypan blue staining and bright field microscopy for samples exposed to heating durations of 2 and 6 minutes alone or with 0.085 mg/ml SWNHs. A Beckman Coulter Vi-Cell instrument quantified cell viability of samples treated with varying SWNH concentration (0, 0.01, 0.085, and 0.333 mg/ml) and heating durations of 0-6 minutes. Spectrophotometer measurements indicated inclusion of SWNHs increased light absorption and attenuation across all wavelengths. Utilizing SWNHs with laser irradiation increased temperature elevation compared to laser heating alone. Greater absorption and higher temperature elevations were observed with increasing SWNH concentration. No inherent toxicity was observed with SWNH inclusion. A more rapid and substantial viability decline was observed over time in samples exposed to SWNHs with laser treatment compared with samples experiencing laser

  19. Sulforaphane – a possible agent in prevention and therapy of cancer

    Directory of Open Access Journals (Sweden)

    Joanna Tomczyk

    2010-11-01

    Full Text Available Sulforaphane (SFN is an isothiocyanate that is naturally present in cruciferous vegetables, with high concentration in broccoli. The results of the most recent studies indicate multi-targeted sulforaphane actions which may contribute to prevention and therapy of cancer. Protective properties of sulforaphane have been observed in every stage of carcinogenesis. The mechanism of protection against the initiation of carcinogenesis by SFN includes modulation of phase I and II xenobiotic-metabolizing enzymes, as well as direct blocking of specific binding sites of carcinogens with the DNA molecule. As a result, sulforaphane inhibits DNA adduct formation, thus reducing the risk of mutations. Further sulforaphane activity is targeted at cancer cells and prevents their expansion due to regulation of proliferation and induction of differentiation or apoptosis. In vitro studies using various types of cancer cells have revealed the ability of SFN to arrest the cell cycle, particularly in G2/M, while SFN at higher concentration is shown to activate apoptotic pathways. The possible SFN anticancer effect in the progression stage of carcinogenesis has been proved by only a few studies, which provide evidence for its antiangiogenic and antimetastatic influence. Additionally, SFN exhibits anti-inflammatory and antibacterial effects relevant to cancer prevention.Apart from the biological activity of SFN, this review also focuses on its bioavailability and tissue distribution as well as individuals’ genetic predispositions as significant factors influencing the potential efficiency of chemoprevention using this compound.

  20. Dynamic fluorescence imaging with molecular agents for cancer detection

    Science.gov (United States)

    Kwon, Sun Kuk

    Non-invasive dynamic optical imaging of small animals requires the development of a novel fluorescence imaging modality. Herein, fluorescence imaging is demonstrated with sub-second camera integration times using agents specifically targeted to disease markers, enabling rapid detection of cancerous regions. The continuous-wave fluorescence imaging acquires data with an intensified or an electron-multiplying charge-coupled device. The work presented in this dissertation (i) assessed dose-dependent uptake using dynamic fluorescence imaging and pharmacokinetic (PK) models, (ii) evaluated disease marker availability in two different xenograft tumors, (iii) compared the impact of autofluorescence in fluorescence imaging of near-infrared (NIR) vs. red light excitable fluorescent contrast agents, (iv) demonstrated dual-wavelength fluorescence imaging of angiogenic vessels and lymphatics associated with a xenograft tumor model, and (v) examined dynamic multi-wavelength, whole-body fluorescence imaging with two different fluorescent contrast agents. PK analysis showed that the uptake of Cy5.5-c(KRGDf) in xenograft tumor regions linearly increased with doses of Cy5.5-c(KRGDf) up to 1.5 nmol/mouse. Above 1.5 nmol/mouse, the uptake did not increase with doses, suggesting receptor saturation. Target to background ratio (TBR) and PK analysis for two different tumor cell lines showed that while Kaposi's sarcoma (KS1767) exhibited early and rapid uptake of Cy5.5-c(KRGDf), human melanoma tumors (M21) had non-significant TBR differences and early uptake rates similar to the contralateral normal tissue regions. The differences may be due to different compartment location of the target. A comparison of fluorescence imaging with NIR vs. red light excitable fluorescent dyes demonstrates that NIR dyes are associated with less background signal, enabling rapid tumor detection. In contrast, animals injected with red light excitable fluorescent dyes showed high autofluorescence. Dual

  1. Cancer Clonal Theory, Immune Escape, and Their Evolving Roles in Cancer Multi-Agent Therapeutics.

    Science.gov (United States)

    Messerschmidt, Jonathan L; Bhattacharya, Prianka; Messerschmidt, Gerald L

    2017-08-12

    The knowledge base of malignant cell growth and resulting targets is rapidly increasing every day. Clonal theory is essential to understand the changes required for a cell to become malignant. These changes are then clues to therapeutic intervention strategies. Immune system optimization is a critical piece to find, recognize, and eliminate all cancer cells from the host. Only by administering (1) multiple therapies that counteract the cancer cell's mutational and externally induced survival traits and (2) by augmenting the immune system to combat immune suppression processes and by enhancing specific tumor trait recognition can cancer begin to be treated with a truly targeted focus. Since the sequencing of the human genome during the 1990s, steady progress in understanding genetic alterations and gene product functions are being unraveled. In cancer, this is proceeding very fast and demonstrates that genetic mutations occur very rapidly to allow for selection of survival traits within various cancer clones. Hundreds of mutations have been identified in single individual cancers, but spread across many clones in the patient's body. Precision oncology will require accurate measurement of these cancer survival-benefiting mutations to develop strategies for effective therapy. Inhibiting these cellular mechanisms is a first step, but these malignant cells need to be eliminated by the host's mechanisms, which we are learning to direct more specifically. Cancer is one of the most complicated cellular aberrations humans have encountered. Rapidly developing significant survival traits require prompt, repeated, and total body measurements of these attributes to effectively develop multi-agent treatment of the individual's malignancy. Focused drug development to inhibit these beneficial mutations is critical to slowing cancer cell growth and, perhaps, triggering apoptosis. In many cases, activation and targeting of the immune system to kill the remaining malignant cells is

  2. Chalcones Enhance TRAIL-Induced Apoptosis in Prostate Cancer Cells

    OpenAIRE

    Ewelina Szliszka; Zenon P. Czuba; Bogdan Mazur; Lukasz Sedek; Andrzej Paradysz; Wojciech Krol

    2009-01-01

    Chalcones exhibit chemopreventive and antitumor effects. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a naturally occurring anticancer agent that induces apoptosis in cancer cells and is not toxic to normal cells. We examined the cytotoxic and apoptotic effect of five chalcones in combination with TRAIL on prostate cancer cells. The cytotoxicity was evaluated by the MTT and LDH assays. The apoptosis was determined using flow cytometry with annexin V-FITC. Our study showe...

  3. Metformin targets c-MYC oncogene to prevent prostate cancer

    OpenAIRE

    Akinyeke, Tunde; Matsumura, Satoko; Wang, Xinying; Wu, Yingjie; Schalfer, Eric D.; Saxena, Anjana; Yan, Wenbo; Logan, Susan K; Li, Xin

    2013-01-01

    Prostate cancer (PCa) is the second leading cause of cancer-related death in American men and many PCa patients develop skeletal metastasis. Current treatment modalities for metastatic PCa are mostly palliative with poor prognosis. Epidemiological studies indicated that patients receiving the diabetic drug metformin have lower PCa risk and better prognosis, suggesting that metformin may have antineoplastic effects. The mechanism by which metformin acts as chemopreventive agent to impede PCa i...

  4. Chemopreventive effects of rofecoxib and folic acid on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats.

    Science.gov (United States)

    Fei, Su Juan; Xiao, Shu Dong; Peng, Yan Shen; Chen, Xiao Yu; Shi, Yao

    2006-01-01

    Epidemiological and experimental studies indicate that non-steroidal anti-inflammatory drugs (NSAIDs) are chemopreventive agents of gastrointestinal cancers, but few studies on gastric cancer have been carried out. A decrease in folic acid supplement and subsequent DNA hypomethylation are related to gastrointestinal cancers, and it has been shown that high-dose folic acid may interfere with gastric carcinogenesis in dogs. The objective of this study was to investigate the effects of rofecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, and folic acid on the chemoprevention of gastric cancer induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in Wistar rats, and to evaluate the cell proliferation of gastric mucosa in different experimental groups. Eighty male Wistar rats were randomly divided into five groups (16 rats in each group). In the control group, the rats were given pure water and basal diet. In the MNNG group, the rats received MNNG in drinking water (100 mg/L) and basal diet. In the MNNG + low-dose rofecoxib group, the rats were given MNNG and rofecoxib 5 mg/kg per day with basal diet. In the MNNG + high-dose rofecoxib group, the rats were given MNNG and rofecoxib 15 mg/kg per day with basal diet. In the MNNG + folic acid group, the rats were given MNNG and folic acid 5 mg/kg per day with basal diet. The experiment was terminated at 50 weeks, and all rats were killed. Blood samples of 3 mL were obtained for measurement of serum folic acid concentrations in the control group, the MNNG group and the MNNG + folic acid group by using chemiluminescent method. The stomach was removed from all rats for histopathological examination and immunohistochemical study. Proliferating cell nuclear antigen (PCNA) expression in gastric epithelial cells was also determined. In the MNNG group, five of 11 rats (45.5%) developed gastric cancer, while in all other four groups no gastric cancer was found (P cancerous tissues was significantly higher than that in the non-cancerous

  5. Early-life exposures to infectious agents and later cancer development.

    Science.gov (United States)

    Vedham, Vidya; Verma, Mukesh; Mahabir, Somdat

    2015-12-01

    There is a growing understanding that several infectious agents are acquired in early life and this is the reason why available vaccines target the new born, infants, and adolescents. Infectious agents are associated with cancer development and it is estimated that about 20% of the world's cancer burden is attributed to infectious agents. There is a growing evidence that certain infectious agents acquired in early life can give rise to cancer development, but estimates of the cancer burden from this early-life acquisition is unknown. In this article, we have selected five cancers (cervical, liver, Burkitt's lymphoma-leukemia, nasopharyngeal carcinoma, and adult T-cell leukemia-lymphoma) and examine their links to infectious agents (HPV, HBV, HCV, EBV, and HTLV-1) acquired in early life. For these agents, the acquisition in early life is from mother-to-child transmission, perinatal contact (with genital tract secretions, amniotic fluids, blood, and breast milk), saliva, sexual intercourse, and blood transfusion. We also discuss prevention strategies, address future directions, and propose mechanisms of action after a long latency period from the time of acquisition of the infectious agent in early life to cancer development. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. Cancer Medicine published by John Wiley & Sons Ltd.

  6. Agent Orange exposure and cancer incidence in Korean Vietnam veterans: a prospective cohort study.

    Science.gov (United States)

    Yi, Sang-Wook; Ohrr, Heechoul

    2014-12-01

    During the Vietnam War, US and allied military sprayed approximately 77 million liters of tactical herbicides including Agent Orange, contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin. To the authors' knowledge, few studies to date have examined the association between Agent Orange exposure and cancer incidence among Korean veterans who were exposed to Agent Orange during the Vietnam War. An Agent Orange exposure index, based on the proximity of the veteran's military unit to the area that was sprayed with Agent Orange, was developed using a geographic information system-based model. Cancer incidence was followed for 180,251 Vietnam veterans from 1992 through 2003. After adjustment for age and military rank, high exposure to Agent Orange was found to significantly increase the risk of all cancers combined (adjusted hazards ratio [aHR], 1.08). Risks for cancers of the mouth (aHR, 2.54), salivary glands (aHR, 6.96), stomach (aHR, 1.14), and small intestine (aHR, 2.30) were found to be significantly higher in the high-exposure group compared with the low-exposure group. Risks for cancers of all sites combined (aHR, 1.02) and for cancers of the salivary glands (aHR, 1.47), stomach (aHR, 1.03), small intestine (aHR, 1.24), and liver (aHR, 1.02) were elevated with a 1-unit increase in the exposure index. Exposure to Agent Orange several decades earlier may increase the risk of cancers in all sites combined, as well as several specific cancers, among Korean veterans of the Vietnam War, including some cancers that were not found to be clearly associated with exposure to Agent Orange in previous cohort studies primarily based on Western populations. © 2014 American Cancer Society.

  7. LC-MS-Based Metabolomic Investigation of Chemopreventive Phytochemical-Elicited Metabolic Events.

    Science.gov (United States)

    Wang, Lei; Yao, Dan; Chen, Chi

    2016-01-01

    Phytochemicals are under intensive investigation for their potential use as chemopreventive agents in blocking or suppressing carcinogenesis. Metabolic interactions between phytochemical and biological system play an important role in determining the efficacy and toxicity of chemopreventive phytochemicals. However, complexities of phytochemical biotransformation and intermediary metabolism pose challenges for studying phytochemical-elicited metabolic events. Metabolomics has become a highly effective technical platform to detect subtle changes in a complex metabolic system. Here, using green tea polyphenols as an example, we describe a workflow of LC-MS-based metabolomics study, covering the procedures and techniques in sample collection, preparation, LC-MS analysis, data analysis, and interpretation.

  8. Prolonged Sulforaphane Treatment Activates Extracellular-Regulated Kinase 1/2 Signaling in Nontumorigenic Colon Cells but not Colon Cancer Cells

    Science.gov (United States)

    Sulforaphane (SFN) is a naturally occurring member of the isothiocyanate family of chemopreventive agents and the induction of cell cycle arrest and apoptosis is a key mechanism by which SFN exerts its colon cancer prevention. However, little is known about the differential effects of SFN on colon c...

  9. Beta-cryptoxanthin reduced lung tumor multiplicity and inhibited lung cancer cell motility by downregulating nicotinic acetylcholine receptor alpha7 signaling

    Science.gov (United States)

    Despite the consistent association between a higher intake of the provitamin A carotenoid beta-cryptoxanthin (BCX) and a lower risk of lung cancer among smokers, potential mechanisms supporting BCX as a chemopreventive agent are needed. We first examined the effects of BCX on 4-[methyl nitrosamino]-...

  10. A review of Agent Orange and its associated oncologic risk of genitourinary cancers.

    Science.gov (United States)

    Chang, Chrystal; Benson, Michael; Fam, Mina M

    2017-11-01

    Agent Orange is an herbicide sprayed widely in Vietnam that is linked to a variety of malignancies in as early as 1991.Since then, there has been concern for, and subsequent interest in studying, the potential connection between Agent Orange and other malignancies. In the past 2 decades, there have been significant changes in the opinion of the National Academy of Science regarding Agent Orange and certain genitourinary malignancies. Herein, we review the literature regarding the potential link between Agent Orange and various urological cancers, including prostate, bladder, testicular, and renal cancers. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Therapeutic strategies with oral fluoropyrimidine anticancer agent, S-1 against oral cancer.

    Science.gov (United States)

    Harada, Koji; Ferdous, Tarannum; Ueyama, Yoshiya

    2017-08-01

    Oral cancer has been recognized as a tumor with low sensitivity to anticancer agents. However, introduction of S-1, an oral cancer agent is improving treatment outcome for patients with oral cancer. In addition, S-1, as a main drug for oral cancer treatment in Japan can be easily available for outpatients. In fact, S-1 exerts high therapeutic effects with acceptable side effects. Moreover, combined chemotherapy with S-1 shows higher efficacy than S-1 alone, and combined chemo-radiotherapy with S-1 exerts remarkable therapeutic effects. Furthermore, we should consider the combined therapy of S-1 and molecular targeting agents right now as these combinations were reportedly useful for oral cancer treatment. Here, we describe our findings related to S-1 that were obtained experimentally and clinically, and favorable therapeutic strategies with S-1 against oral cancer with bibliographic considerations.

  12. Moringa oleifera as an Anti-Cancer Agent against Breast and Colorectal Cancer Cell Lines.

    Directory of Open Access Journals (Sweden)

    Abdulrahman Khazim Al-Asmari

    Full Text Available In this study we investigated the anti-cancer effect of Moringa oleifera leaves, bark and seed extracts. When tested against MDA-MB-231 and HCT-8 cancer cell lines, the extracts of leaves and bark showed remarkable anti-cancer properties while surprisingly, seed extracts exhibited hardly any such properties. Cell survival was significantly low in both cells lines when treated with leaves and bark extracts. Furthermore, a striking reduction (about 70-90% in colony formation as well as cell motility was observed upon treatment with leaves and bark. Additionally, apoptosis assay performed on these treated breast and colorectal cancer lines showed a remarkable increase in the number of apoptotic cells; with a 7 fold increase in MD-MB-231 to an increase of several fold in colorectal cancer cell lines. However, no significant apoptotic cells were detected upon seeds extract treatment. Moreover, the cell cycle distribution showed a G2/M enrichment (about 2-3 fold indicating that these extracts effectively arrest the cell progression at the G2/M phase. The GC-MS analyses of these extracts revealed numerous known anti-cancer compounds, namely eugenol, isopropyl isothiocynate, D-allose, and hexadeconoic acid ethyl ester, all of which possess long chain hydrocarbons, sugar moiety and an aromatic ring. This suggests that the anti-cancer properties of Moringa oleifera could be attributed to the bioactive compounds present in the extracts from this plant. This is a novel study because no report has yet been cited on the effectiveness of Moringa extracts obtained in the locally grown environment as an anti-cancer agent against breast and colorectal cancers. Our study is the first of its kind to evaluate the anti-malignant properties of Moringa not only in leaves but also in bark. These findings suggest that both the leaf and bark extracts of Moringa collected from the Saudi Arabian region possess anti-cancer activity that can be used to develop new drugs for

  13. Moringa oleifera as an Anti-Cancer Agent against Breast and Colorectal Cancer Cell Lines.

    Science.gov (United States)

    Al-Asmari, Abdulrahman Khazim; Albalawi, Sulaiman Mansour; Athar, Md Tanwir; Khan, Abdul Quaiyoom; Al-Shahrani, Hamoud; Islam, Mozaffarul

    2015-01-01

    In this study we investigated the anti-cancer effect of Moringa oleifera leaves, bark and seed extracts. When tested against MDA-MB-231 and HCT-8 cancer cell lines, the extracts of leaves and bark showed remarkable anti-cancer properties while surprisingly, seed extracts exhibited hardly any such properties. Cell survival was significantly low in both cells lines when treated with leaves and bark extracts. Furthermore, a striking reduction (about 70-90%) in colony formation as well as cell motility was observed upon treatment with leaves and bark. Additionally, apoptosis assay performed on these treated breast and colorectal cancer lines showed a remarkable increase in the number of apoptotic cells; with a 7 fold increase in MD-MB-231 to an increase of several fold in colorectal cancer cell lines. However, no significant apoptotic cells were detected upon seeds extract treatment. Moreover, the cell cycle distribution showed a G2/M enrichment (about 2-3 fold) indicating that these extracts effectively arrest the cell progression at the G2/M phase. The GC-MS analyses of these extracts revealed numerous known anti-cancer compounds, namely eugenol, isopropyl isothiocynate, D-allose, and hexadeconoic acid ethyl ester, all of which possess long chain hydrocarbons, sugar moiety and an aromatic ring. This suggests that the anti-cancer properties of Moringa oleifera could be attributed to the bioactive compounds present in the extracts from this plant. This is a novel study because no report has yet been cited on the effectiveness of Moringa extracts obtained in the locally grown environment as an anti-cancer agent against breast and colorectal cancers. Our study is the first of its kind to evaluate the anti-malignant properties of Moringa not only in leaves but also in bark. These findings suggest that both the leaf and bark extracts of Moringa collected from the Saudi Arabian region possess anti-cancer activity that can be used to develop new drugs for treatment of breast

  14. Towards safety of oral anti-cancer agents, the need to educate our pharmacists

    Directory of Open Access Journals (Sweden)

    Sanaa Saeed Mekdad

    2017-01-01

    Full Text Available Introduction: The global prevalence of cancer is rising. Use of oral anticancer medications has expanded exponentially. Knowledge about these medications as well as safe handling guidelines has not kept abreast with the rapidity these medications are applied in clinical practice. They pose serious hazards on all personal involved in handling these medications as well as on patients and their caregivers. We addressed the gaps in knowledge and safe handling of oral anticancer agents among pharmacists in institutional based cancer care. Materials and Methods: We used a 41 item questionnaire to explore three domains, pharmacists’ knowledge, safe handling practice and confidence and self-improving strategies towards these agents among pharmacists in multicentre specialized cancer care. Results: Participants included 120 pharmacists dedicated to handle and dispense oral anticancer agents. About 20% of Pharmacists have adequate knowledge about oral anticancer agents. Less than 50% apply safe handling principles adequately. Only a quarter are confident in educating cancer patients and their caregivers about Oral Anti-Cancer Agents. Conclusions: Pharmacists’ knowledge about Oral Anticancer agents needs to be improved. Safe handling and dispensing practice of these medications should be optimized. Pharmacists’ confidence towards educating patients and their caregiver needs to be addressed. Enhancing safety of oral anticancer agents should be a priority. Involving all key players, research and quality improving projects are needed to improve all aspects of the safety of oral anticancer agents.

  15. Understanding Carcinogenesis for Fighting Oral Cancer

    Directory of Open Access Journals (Sweden)

    Takuji Tanaka

    2011-01-01

    Full Text Available Oral cancer is one of the major global threats to public health. Oral cancer development is a tobacco-related multistep and multifocal process involving field cancerization and carcinogenesis. The rationale for molecular-targeted prevention of oral cancer is promising. Biomarkers of genomic instability, including aneuploidy and allelic imbalance, are able to measure the cancer risk of oral premalignancies. Understanding of the biology of oral carcinogenesis will give us important advances for detecting high-risk patients, monitoring preventive interventions, assessing cancer risk, and pharmacogenomics. In addition, novel chemopreventive agents based on molecular mechanisms and targets against oral cancers will be derived from research using appropriate animal carcinogenesis models. New approaches, such as interventions with molecular-targeted agents and agent combinations in high-risk oral individuals, are undoubtedly needed to reduce the devastating worldwide consequences of oral malignancy.

  16. Association of cancer metabolism-related proteins with oral carcinogenesis – indications for chemoprevention and metabolic sensitizing of oral squamous cell carcinoma?

    Science.gov (United States)

    2014-01-01

    Background Tumor metabolism is a crucial factor for the carcinogenesis of oral squamous cell carcinoma (OSCC). Methods Expression of IGF-R1, glycolysis-related proteins (GLUT-1, HK 2, PFK-1, LDHA, TKTL1), mitochondrial enzymes (SDHA, SDHB, ATP synthase) were analyzed in normal oral mucosa (n = 5), oral precursor lesions (simple hyperplasia, n = 11; squamous intraepithelial neoplasia, SIN I-III, n = 35), and OSCC specimen (n = 42) by immunohistochemistry and real-time polymerase chain reaction (qPCR) analysis in OSCC cell lines. Metabolism-related proteins were correlated with proliferation activity (Ki-67) and apoptotic properties (TUNEL assay) in OSCC. Specificity of antibodies was confirmed by western blotting in cancer cell lines. Results Expression of IGF-R1, glycolysis-related proteins (GLUT-1, HK 2, LDHA, TKTL1), and mitochondrial enzymes (SDHA, SDHB, ATP synthase) were significantly increased in the carcinogenesis of OSCC. Metabolic active regions of OSCC were strongly correlated with proliferating cancer (Ki-67+) cells without detection of apoptosis (TUNEL assay). Conclusions This study provides the first evidence of the expression of IGF-R1, glycolysis-related proteins GLUT-1, HK 2, PFK-1, LDHA, and TKTL1, as well as mitochondrial enzymes SDHA, SDHB, and ATP synthase in the multi-step carcinogenesis of OSCC. Both, hypoxia-related glucose metabolism and mitochondrial oxidative phosphorylation characteristics are associated with the carcinogenesis of OSCC. Acidosis and OXPHOS may drive a metabolic shift towards the pentose phosphate pathway (PPP). Therefore, inhibition of the PPP, glycolysis, and targeted anti-mitochondrial therapies (ROS generation) by natural compounds or synthetic vitamin derivatives may act as sensitizer for apoptosis in cancer cells mediated by adjuvant therapies in OSCC. PMID:25048361

  17. Association of cancer metabolism-related proteins with oral carcinogenesis - indications for chemoprevention and metabolic sensitizing of oral squamous cell carcinoma?

    Science.gov (United States)

    Grimm, Martin; Cetindis, Marcel; Lehmann, Max; Biegner, Thorsten; Munz, Adelheid; Teriete, Peter; Kraut, Wiebke; Reinert, Siegmar

    2014-07-21

    Tumor metabolism is a crucial factor for the carcinogenesis of oral squamous cell carcinoma (OSCC). Expression of IGF-R1, glycolysis-related proteins (GLUT-1, HK 2, PFK-1, LDHA, TKTL1), mitochondrial enzymes (SDHA, SDHB, ATP synthase) were analyzed in normal oral mucosa (n = 5), oral precursor lesions (simple hyperplasia, n = 11; squamous intraepithelial neoplasia, SIN I-III, n = 35), and OSCC specimen (n = 42) by immunohistochemistry and real-time polymerase chain reaction (qPCR) analysis in OSCC cell lines. Metabolism-related proteins were correlated with proliferation activity (Ki-67) and apoptotic properties (TUNEL assay) in OSCC. Specificity of antibodies was confirmed by western blotting in cancer cell lines. Expression of IGF-R1, glycolysis-related proteins (GLUT-1, HK 2, LDHA, TKTL1), and mitochondrial enzymes (SDHA, SDHB, ATP synthase) were significantly increased in the carcinogenesis of OSCC. Metabolic active regions of OSCC were strongly correlated with proliferating cancer (Ki-67+) cells without detection of apoptosis (TUNEL assay). This study provides the first evidence of the expression of IGF-R1, glycolysis-related proteins GLUT-1, HK 2, PFK-1, LDHA, and TKTL1, as well as mitochondrial enzymes SDHA, SDHB, and ATP synthase in the multi-step carcinogenesis of OSCC. Both, hypoxia-related glucose metabolism and mitochondrial oxidative phosphorylation characteristics are associated with the carcinogenesis of OSCC. Acidosis and OXPHOS may drive a metabolic shift towards the pentose phosphate pathway (PPP). Therefore, inhibition of the PPP, glycolysis, and targeted anti-mitochondrial therapies (ROS generation) by natural compounds or synthetic vitamin derivatives may act as sensitizer for apoptosis in cancer cells mediated by adjuvant therapies in OSCC.

  18. Targeted Cancer Diagnostic and Therapeutic Agents: Delivery by Carriers or Conjugation

    Directory of Open Access Journals (Sweden)

    Mohsen Mohammadgholi

    2016-07-01

    Full Text Available Receptors and proteins are overexpressed in many human cancer cell membranes rather than normal tissues and are considered as the main molecular targets. Specific tumor- targeting molecules which have high affinity for these receptors can be valuable tools as carrier molecules for targeted cancer therapy and imaging. Pharmacokinetics and bioavailability of diagnostic and therapeutic agents are very important. Poor selectivity of cancer therapeutic agents causes toxicity on normal cells that limits maximum effective dose. The Attachment of these agents to macromolecules or their installation on carriers is currently under investigation. This article presents recent developments in the field of targeting agents and introduces different carriers and their applications in the diagnosis and treatment of cancer.

  19. Anthocyanin-rich black currant (Ribes nigrum L.) extract affords chemoprevention against diethylnitrosamine-induced hepatocellular carcinogenesis in rats.

    Science.gov (United States)

    Bishayee, Anupam; Mbimba, Thomas; Thoppil, Roslin J; Háznagy-Radnai, Erzsébet; Sipos, Péter; Darvesh, Altaf S; Folkesson, Hans G; Hohmann, Judit

    2011-11-01

    Anthocyanins are known to possess potent anticarcinogenic properties against several cancers thus demonstrating potential for cancer prevention. Black currant (Ribes nigrum L., Grossulariaceae) fruits have a high anthocyanin content. This "superfruit" is known to possess various pharmacological effects including alleviation of chronic oxidative stress and inflammation. In contrast to a large volume of literature on the health benefits of black currant, limited evidence on antitumor effects of black currant exists with virtually no data on the prevention of experimental carcinogenesis. In the current study, we have investigated the chemopreventive effects of an anthocyanin-rich black currant skin extract (BCSE) utilizing our well-characterized model of rat liver carcinogenesis. Initiation of hepatocarcinogenesis was done by intraperitoneal injection of diethylnitrosamine (DENA) followed by promotion with phenobarbital. The rats were exposed to dietary BCSE for 4 weeks prior to initiation, and the treatment was continued for 22 consecutive weeks. BCSE dose-dependently decreased the incidence, total number, multiplicity, size and volume of preneoplastic hepatic nodules. The antihepatocarcinogenic effect of BCSE was confirmed by histopathological examination of liver sections. Immunohistochemical analysis of proliferating cell nuclear antigen and DNA fragmentation revealed BCSE-mediated inhibition of abnormal cell proliferation and induction of apoptosis in DENA-induced rat liver tumorigenesis respectively. Mechanistic studies revealed that BCSE-mediated proapototic signal during experimental hepatocarcinogenesis may be propagated via the up-regulation of Bax and down-regulation of Bcl-2 expression at the translational level. These results along with a safety profile of BCSE encourage the development of black currant bioactive constituents as chemopreventive agents for human liver cancer. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Chemopreventive effects of Cuminum cyminum in chemically induced forestomach and uterine cervix tumors in murine model systems.

    Science.gov (United States)

    Gagandeep; Dhanalakshmi, Sivanandhan; Méndiz, Ester; Rao, Agra Ramesha; Kale, Raosaheb Kathalupant

    2003-01-01

    Lately, a strong correlation has been established between diet and cancer. For ages, cumin has been a part of the diet. It is a popular spice regularly used as a flavoring agent in a number of ethnic cousins. In the present study, cancer chemopreventive potentials of different doses of a cumin seed-mixed diet were evaluated against benzo(a)pyrene [B(a)P]-induced forestomach tumorigenesis and 3-methylcholanthrene (MCA)-induced uterine cervix tumorigenesis. Results showed a significant inhibition of stomach tumor burden (tumors per mouse) by cumin. Tumor burden was 7.33 +/- 2.10 in the B(a)P-treated control group, whereas it reduced to 3.10 +/- 0.57 (P cumin seeds. Cervical carcinoma incidence, compared with the MCA-treated control group (66.67%), reduced to 27.27% (P cumin seeds and to 12.50% (P cumin seeds. The effect of 2.5 and 5% cumin seed-mixed diets was also examined on carcinogen/xenobiotic metabolizing phase I and phase II enzymes, antioxidant enzymes, glutathione content, lactate dehydrogenase (LDH), and lipid peroxidation in the liver of Swiss albino mice. Levels of cytochrome P-450 (cyt P-450) and cytochrome b5 (cyt b(5)) were significantly augmented (P cumin seed diet. The levels of cyt P-450 reductase and cyt b(5) reductase were increased (significance level being from P cumin. Among the phase II enzymes, glutathione S-transferase specific activity increased (P cumin. The activities of glutathione peroxidase and glutathione reductase remained unaltered by both doses of cumin. The level of reduced glutathione measured as nonprotein sulfhydryl content was elevated (significance level being from P cumin. Lipid peroxidation measured as formation of MDA production showed significant inhibition (P cumin. LDH activity remained unaltered by both doses of cumin. The results strongly suggest the cancer chemopreventive potentials of cumin seed and could be attributed to its ability to modulate carcinogen metabolism.

  1. Novel Targeted Agents and Immunotherapy in Breast Cancer.

    Science.gov (United States)

    Mayer, Ingrid A; Dent, Rebecca; Tan, Tira; Savas, Peter; Loi, Sherene

    2017-01-01

    The treatment of breast cancer is generally determined according to breast cancer subtype: hormone receptor-positive (luminal), triple-negative (basal-like), and HER2-overexpressing breast cancer. Recent years have seen the development of exciting novel and potent therapeutics based on molecular pathways, immune modulation, and antibody conjugates. In this article, we cover new and emerging therapeutic areas and ongoing clinical trials that may result in further improvements in breast cancer outcomes.

  2. Developing Inhibitors of Translesion DNA Synthesis as Therapeutic Agents against Lung Cancer

    Science.gov (United States)

    2015-12-01

    AWARD NUMBER: W81XWH-13-1-0238 TITLE: Developing Inhibitors of Translesion DNA Synthesis as Therapeutic Agents against Lung Cancer PRINCIPAL...of Translesion DNA Synthesis as Therapeutic Agents against Lung Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...Oxygen-rich environments can create pro- mutagenic DNA lesions such as 8-oxoguanine (8-oxo-G) that can be misreplicated during translesion DNA synthesis

  3. Vitamin D in childhood cancer: a promising anticancer agent?

    Science.gov (United States)

    Genc, D Bahar; Ozkan, M Alp; Buyukgebiz, Atilla

    2013-07-01

    Children diagnosed and treated for cancer are vulnerable to Vitamin D deficiency depending on many factors. The Vitamin D status in children with cancer has been mostly regarded as a contributory factor for skeletal pathologies so far. However, the calcitriol was found to promote cell differentiation, inhibit malignant proliferation, and exhibit antiinflammatory, proapoptotic and antiangiogenic properties. In addition to this, numerous epidemiological studies link Vitamin D and cancer and indicate to possible role of Vitamin D in cancer pathogenesis and progression. This article aims to provide an overview of the possible role of Vitamin D deficiency in childhood cancer in terms of prevention and treatment.

  4. Nutraceuticals as potential therapeutic agents for colon cancer: a review

    Directory of Open Access Journals (Sweden)

    Palaniselvam Kuppusamy

    2014-06-01

    Full Text Available Colon cancer is a world-wide health problem and the second-most dangerous type of cancer, affecting both men and women. The modern diet and lifestyles, with high meat consumption and excessive alcohol use, along with limited physical activity has led to an increasing mortality rate for colon cancer worldwide. As a result, there is a need to develop novel and environmentally benign drug therapies for colon cancer. Currently, nutraceuticals play an increasingly important role in the treatment of various chronic diseases such as colon cancer, diabetes and Alzheimer׳s disease. Nutraceuticals are derived from various natural sources such as medicinal plants, marine organisms, vegetables and fruits. Nutraceuticals have shown the potential to reduce the risk of colon cancer and slow its progression. These dietary substances target different molecular aspects of colon cancer development. Accordingly, this review briefly discusses the medicinal importance of nutraceuticals and their ability to reduce the risk of colorectal carcinogenesis.

  5. Short-term Intervention to Revert Premalignant Lesions as Strategy to Prevent Gastrointestinal Cancers.

    Science.gov (United States)

    Han, Young-Min; Park, Jong-Min; Lee, Ho-Jae; Kim, Eun-Hee; Hahm, Ki Baik

    2013-12-01

    "Prevention might be better than treatment in cancer treatment" is brief conclusion drawn from war on cancer through National Cancer Act of 1971 by U.S. President Richard Nixon. However, the clinical practice of chemoprevention is still in its infancy in spite of a wealth of data showing its effectiveness in experimental animals as well as in vitro mechanism research. Recent advances in either high throughput analysis including cancer genomes and tailored medicine or molecular targeted therapeutics, preventive strategies also should be changes as previous preventive strategies including phytoceuticals, life-style modification, and some empirical agents. Furthermore, molecular targeted therapeutics achieved high goal of effectiveness under the concept of therapeutic or preventive "synthetic lethality", of which extended application can be included within the scope of chemoprevention. Here, we will summarize several recent advances in chemopreventive strategy objected to justify optimism that chemoprevention will be an effective approach for the control of human cancer. siTRP (short-term intervention to revert premalignancy) strategy will be introduced for cancers in gastroenterology.

  6. Prediction of survival in resected non-small cell lung cancer using a protein expression-based risk model: implications for personalized chemoprevention and therapy.

    Science.gov (United States)

    Gold, Kathryn A; Kim, Edward S; Liu, Diane D; Yuan, Ping; Behrens, Carmen; Solis, Luisa M; Kadara, Humam; Rice, David C; Wistuba, Ignacio I; Swisher, Stephen G; Hofstetter, Wayne L; Lee, J Jack; Hong, Waun K

    2014-04-01

    Patients with resected non-small cell lung cancer (NSCLC) are at risk for recurrence of disease, but we do not have tools to predict which patients are at highest risk. We set out to create a risk model incorporating both clinical data and biomarkers. We assembled a comprehensive database with archival tissues and clinical follow-up from patients with NSCLC resected between 2002 and 2005. Twenty-one proteins identified from our preclinical studies as related to lung carcinogenesis were investigated, including pathways related to metabolism, DNA repair, inflammation, and growth factors. Expression of proteins was quantified using immunohistochemistry. Immunohistochemistry was chosen because it is widely available and can be performed on formalin-fixed paraffin-embedded specimens. Cox models were fitted to estimate effects of clinical factors and biomarkers on recurrence-free survival (RFS) and overall survival (OS). A total of 370 patients are included in our analysis. With median follow-up of 5.3 years, median OS is 6.4 years. A total of 209 cases with recurrence or death were observed. Multicovariate risk models for RFS and OS were developed including relevant biomarkers, age, and stage. Increased expression of phospho-adenosine monophosphate-activated protein kinase (pAMPK), phospho-mTOR (pmTOR), epithelial cell adhesion molecule (EpCAM), and calcium/calmodulin-dependent serine protein kinase were significant (P < 0.05) predictors for favorable RFS; insulin receptor, chemokine (C-X-C motif) receptor 2 (CXCR2), and insulin-like growth factor-1 receptor predicted for unfavorable RFS. Significant (P < 0.05) predictors for favorable OS include pAMPK, pmTOR, and EpCAM; CXCR2 and flap structure-specific endonuclease-1 predicted unfavorable OS. We have developed a comprehensive risk model predictive for recurrence in our large retrospective database, which is one of the largest reported series of resected NSCLC. ©2013 AACR.

  7. Trimethoxy-resveratrol and piceatannol administered orally suppress and inhibit tumor formation and growth in prostate cancer xenografts

    Science.gov (United States)

    Resveratrol (Res) is recognized as a promising cancer chemoprevention dietary polyphenol with antioxidative, anti-inflammatory and anticancer properties. However, the role of its analogues in prostate cancer (PCa) chemoprevention is still unknown. METHODS. We synthesized natural and synthetic anal...

  8. Development of Holmium 166-chitosan complex as a radiopharmaceutical agent for liver cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Jei Man; Nam, Soon Chul; Park, Sun Joo; Moon, Eun Yi; Lee, Won Yong; Shin, Dong Hyuk; Cho, Eun Hee [Korea Atomic Energy Research Instisute, Taejon (Korea, Republic of)

    1997-09-01

    Effective therapeutic methods for cancer disease should be developed because the frequency of cancer disease is being increased rapidly. But there is no effective therapeutic method for treating these disease until now. The purpose of this research is to gain the clinical approval of Holmium{sup 166}-Chitosan complex as a radiopharmaceutical agent for liver cancer. We finished the preclinical test of Holmium{sup 166}-Chitosan complex and got the approval for clinical trial of this agent. 12 refs., 11 tabs., 9 figs. (author)

  9. Dietary phytochemicals as epigenetic modifiers in cancer: Promise and challenges.

    Science.gov (United States)

    Shankar, Eswar; Kanwal, Rajnee; Candamo, Mario; Gupta, Sanjay

    2016-10-01

    The influence of diet and environment on human health has been known since ages. Plant-derived natural bioactive compounds (phytochemicals) have acquired an important role in human diet as potent antioxidants and cancer chemopreventive agents. In past few decades, the role of epigenetic alterations such as DNA methylation, histone modifications and non-coding RNAs in the regulation of mammalian genome have been comprehensively addressed. Although the effects of dietary phytochemicals on gene expression and signaling pathways have been widely studied in cancer, the impact of these dietary compounds on mammalian epigenome is rapidly emerging. The present review outlines the role of different epigenetic mechanisms in the regulation and maintenance of mammalian genome and focuses on the role of dietary phytochemicals as epigenetic modifiers in cancer. Above all, the review focuses on summarizing the progress made thus far in cancer chemoprevention with dietary phytochemicals, the heightened interest and challenges in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Chalcones Enhance TRAIL-Induced Apoptosis in Prostate Cancer Cells

    Science.gov (United States)

    Szliszka, Ewelina; Czuba, Zenon P; Mazur, Bogdan; Sedek, Lukasz; Paradysz, Andrzej; Krol, Wojciech

    2009-01-01

    Chalcones exhibit chemopreventive and antitumor effects. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a naturally occurring anticancer agent that induces apoptosis in cancer cells and is not toxic to normal cells. We examined the cytotoxic and apoptotic effect of five chalcones in combination with TRAIL on prostate cancer cells. The cytotoxicity was evaluated by the MTT and LDH assays. The apoptosis was determined using flow cytometry with annexin V-FITC. Our study showed that all five tested chalcones: chalcone, licochalcone-A, isobavachalcone, xanthohumol, butein markedly augmented TRAIL-mediated apoptosis and cytotoxicity in prostate cancer cells and confirmed the significant role of chalcones in chemoprevention of prostate cancer. PMID:20161998

  11. Chalcones Enhance TRAIL-Induced Apoptosis in Prostate Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ewelina Szliszka

    2009-12-01

    Full Text Available Chalcones exhibit chemopreventive and antitumor effects. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL is a naturally occurring anticancer agent that induces apoptosis in cancer cells and is not toxic to normal cells. We examined the cytotoxic and apoptotic effect of five chalcones in combination with TRAIL on prostate cancer cells. The cytotoxicity was evaluated by the MTT and LDH assays. The apoptosis was determined using flow cytometry with annexin V-FITC. Our study showed that all five tested chalcones: chalcone, licochalcone-A, isobavachalcone, xanthohumol, butein markedly augmented TRAIL-mediated apoptosis and cytotoxicity in prostate cancer cells and confirmed the significant role of chalcones in chemoprevention of prostate cancer.

  12. Risk of cancer in patients using glucose-lowering agents

    DEFF Research Database (Denmark)

    Andersson, Charlotte; Vaag, Allan; Selmer, Christian

    2012-01-01

    To study the association between exposures to glucose-lowering therapy and risk of cancer using the nationwide administrative registers in Denmark.......To study the association between exposures to glucose-lowering therapy and risk of cancer using the nationwide administrative registers in Denmark....

  13. Consequences of using escharotic agents as primary treatment for nonmelanoma skin cancer.

    Science.gov (United States)

    McDaniel, Shana; Goldman, Glenn D

    2002-12-01

    The use of escharotic or caustic pastes to treat skin cancer is based on the centuries-old observation that selected minerals and plant extracts may be used to destroy certain skin lesions. Zinc chloride and Sanguinaria canadensis (bloodroot) are 2 agents that are used as part of the Mohs chemosurgery fixed-tissue technique. The use of escharotics without surgery has been discredited by allopathic medicine but persists and is promoted among alternative practitioners. Patients may now purchase "herbal supplements" for the primary self-treatment of skin cancer, and physicians will see patients who elect this therapy for their skin cancers. We reviewed the history of escharotic use for skin disease and performed an Internet search for the availability and current use of escharotics. Our search located numerous agents for purchase via the Internet that are advertised as highly successful treatments for skin cancer. We report 4 cases from our practice in which escharotic agents were used by patients to treat basal cell carcinomas in lieu of the recommended conventional treatment. One patient had a complete clinical response, but had a residual tumor on follow-up biopsy. A second patient successfully eradicated all tumors, but severe scarring ensued. A third patient disagreed with us regarding his care and was lost to follow-up. One patient presented with a nasal basal cell carcinoma that "healed" for several years following treatment elsewhere with an escharotic agent but recurred deeply and required an extensive resection. The lesion has since metastasized. Escharotic agents are available as herbal supplements and are being used by patients for the treatment of skin cancer. The efficacy of these agents is unproven and their content is unregulated. Serious consequences may result from their use. Conventional medicine has an excellent track record in treating skin cancer. Physicians should recommend against the use of escharotic agents for skin cancer, and the Food and

  14. Crocetin: an agent derived from saffron for prevention and therapy for cancer.

    Science.gov (United States)

    Gutheil, William G; Reed, Gregory; Ray, Amitabha; Anant, Shrikant; Dhar, Animesh

    2012-01-01

    Cancer is one of the leading causes of death in the United States and accounts for approximately 8 million deaths per year worldwide. Although there is an increasing number of therapeutic options available for patients with cancer, their efficacy is time-limited and non-curative. Approximately 50-60% cancer patients in the United States utilize agents derived from different parts of plants or nutrients (complementary and alternative medicine), exclusively or concurrently with traditional therapeutic regime such as chemotherapy and/or radiation therapy. The need for new drugs has prompted studies evaluating possible anti-cancer agents in fruits, vegetables, herbs and spices. Saffron, a spice and a food colorant present in the dry stigmas of the plant Crocus sativus L., has been used as an herbal remedy for various ailments including cancer by the ancient Arabian, Indian and Chinese cultures. Crocetin, an important carotenoid constituent of saffron, has shown significant potential as an anti-tumor agent in animal models and cell culture systems. Crocetin affects the growth of cancer cells by inhibiting nucleic acid synthesis, enhancing anti-oxidative system, inducing apoptosis and hindering growth factor signaling pathways. This review discusses the studies on cancer preventive potential of crocetin and its future use as an anticancer agent.

  15. Targeted Agents Active Against Breast Cancer: Q&A

    Science.gov (United States)

    ALTTO was a clinical trial designed to determine whether the combination of the monoclonal antibody trastuzumab (Herceptin) and the drug lapatinib (Tykerb) was more effective in treating HER2/ErbB2-positive breast cancer when combined with chemotherapy.

  16. Metals and Breast Cancer: Risk Factors or Healing Agents?

    Directory of Open Access Journals (Sweden)

    Ana-Maria Florea

    2011-01-01

    Full Text Available Metals and metal compounds are part of our environment. Several metals are essential for physiological functions (e.g., zinc or magnesium; while the beneficial effects of others are uncertain (e.g., manganese, some metals are proven to be toxic (e.g., mercury, lead. Additionally there are organic metal compounds; some of them are extremely toxic (e.g., trimethyltin, methylmercury, but there is very little knowledge available how they are handled by organisms. Scientific evidence indicates that long-term exposure to (some metallic compounds induces different forms of cancer, including breast cancer. On the other side, several metal compounds have clinical use in treating life-threatening diseases such as cancer. In this paper we discuss the recent literature that shows a correlation between metal exposure and breast cancer.

  17. Potential New Pharmacological Agents Derived From Medicinal Plants for the Treatment of Pancreatic Cancer.

    Science.gov (United States)

    Azimi, Haniye; Khakshur, Ali Asghar; Abdollahi, Mohammad; Rahimi, Roja

    2015-01-01

    In the present article, we reviewed plants and phytochemical compounds demonstrating beneficial effects in pancreatic cancer to find new sources of pharmaceutical agents. For this purpose, Scopus, PubMed, Web of Science, and Google scholar were searched for plants or herbal components with beneficial effects in the treatment of pancreatic cancer. Data were collected up to January 2013. The search terms were "plant," "herb," "herbal therapy," or "phytotherapy" and "pancreatic cancer" or "pancreas." All of the human in vivo and in vitro studies were included. According to studies, among diverse plants and phytochemicals, 12 compounds including apigenin, genistein, quercetin, resveratrol, epigallocatechin gallate, benzyl isothiocyanate, sulforaphane, curcumin, thymoquinone, dihydroartemisinin, cucurbitacin B, and perillyl alcohol have beneficial action against pancreatic cancer cells through 4 or more mechanisms. Applying their plausible synergistic effects can be an imperative approach for finding new efficient pharmacological agents in the treatment of pancreatic cancer.

  18. Tanshinones as Effective Therapeutic Agents for Prostate Cancer

    Science.gov (United States)

    2011-06-01

    prostate cancer research. The use of plants for medicinal purposes is as old as human history . All traditional and indigenous healing sys- tems used...basis for most modern pharmaceutical drugs. Herbal medicines usually contain multiple bioactive compo- nents with specific biological activities and...are also used as alter- native therapeutic or preventive regimens for individuals with cancer.1 Some of those herbal medicines have been used for cen

  19. Chemopreventive potential of Triphala (a composite Indian drug) on Benzo(a)pyrene induced forestomach tumorigenesis in murine tumor model system

    Energy Technology Data Exchange (ETDEWEB)

    Deep, G.; Dhirman, M.; Rao, A.R.; Kale, R.K. [Jawaharlan Nehru Univ., New Delhi (India). Radiation and Cancer Biology Laboratory

    2005-12-15

    The present work is probably the first report on cancer chemopreventive potential of Triphala, a combination of fruit powder of three different plants namely Terminalia chebula, Terminalia belerica and Emblica officinalis. Triphala is a popular formulation of the Ayurvedic system of medicine. Our findings have shown that Triphala in diet has significantly reduced the benzo(a)pyrene [B(a)P] induced forestomach papillomagenesis in mice. In the short term treatment groups, the tumor incidences were lowered to 77.77% by both doses of Triphala mixed diet. In the case of long-term treatment the tumor incidences were reduced to 66.66% and 62.50% respectively by 2.5% and 5% triphala containing diet. Tumor burden was 7.27{+-}1.16 in the B(a)P treated control group, whereas it reduced to 3.00{+-}0.82 (p<0.005) by 2.5% dose and 2.33 +/- 1.03 (p<0.001) by 5% dose of Triphala. In long-term studies the tumor burden was reduced to 2.17{+-}0.75 (p<0.001) and 2.00{+-}0.71 (p<0.001) by 2.5% and 5% diet of Triphala, respectively. It was important to observe that Triphala was more effective in reducing tumor incidences compared to its individual constituents. Triphala also significantly increased the antioxidant status of animals which might have contributed to the chemoprevention. It was inferred that the concomitant use of multiple agents seemed to have a high degree of chemoprevention potential.

  20. Antioxidative and Chemopreventive Properties of Vernonia amygdalina and Garcinia biflavonoid

    Directory of Open Access Journals (Sweden)

    Olatunde Owoeye

    2011-06-01

    Full Text Available Recently, considerable attention has been focused on dietary and medicinal phytochemicals that inhibit, reverse or retard diseases caused by oxidative and inflammatory processes. Vernonia amygdalina is a perennial herb belonging to the Asteraceae family. Extracts of the plant have been used in various folk medicines as remedies against helminthic, protozoal and bacterial infections with scientific support for these claims. Phytochemicals such as saponins and alkaloids, terpenes, steroids, coumarins, flavonoids, phenolic acids, lignans, xanthones, anthraquinones, edotides and sesquiterpenes have been extracted and isolated from Vernonia amygdalina. These compounds elicit various biological effects including cancer chemoprevention. Garcinia kola (Guttiferae seed, known as “bitter kola”, plays an important role in African ethnomedicine and traditional hospitality. It is used locally to treat illnesses like colds, bronchitis, bacterial and viral infections and liver diseases. A number of useful phytochemicals have been isolated from the seed and the most prominent of them is the Garcinia bioflavonoids mixture called kolaviron. It has well-defined structure and an array of biological activities including antioxidant, antidiabetic, antigenotoxic and hepatoprotective properties. The chemopreventive properties of Vernonia amygdalina and Garcinia biflavonoids have been attributed to their abilities to scavenge free radicals, induce detoxification, inhibit stress response proteins and interfere with DNA binding activities of some transcription factors.

  1. Biomarkers of Selenium Chemoprevention of Prostate Cancer

    Science.gov (United States)

    2005-01-01

    3.0 STKI5 0.5 Ras-like protein TclO 3.8 Mitosin 0.5 GTPase activating factor-2 4.4 thymidylate synthase 0.2 RAN-binding protein 8 3.1 chromatin...0.2 factor 1I Cyclin A 0.3 CDP-DAG synthase 2.3 Cyclin E2 0.3 phospholipase C 134 2.1 MCM6 0.5 receptor of retinoic acid 5.0 Ki67a 0.2 dual...deoxyhypusine synthase 0.42 0.48 1.89 1.10 Hs.21894 ARHCL1 ras homolog gene family, member C like 1 0.60 1.59 0.82 1.07 Hs.424551 P24B integral type I

  2. Cancer Chemopreventive Property of Bidens pilosa Methanolic ...

    African Journals Online (AJOL)

    Bidens pilosa (Asteraceae) is widely grown throughout in India. The effects of different doses (200 and 400 mg/kg of body weight) of methanolic extract of the whole plant was on drug metabolizing Phase-I and Phase-II enzymes, antioxidant enzymes, lactate dehydrogenase, and lipid peroxidation in the liver of 7-week-old ...

  3. Cancer chemopreventive property of Bidens pilosa methanolic ...

    African Journals Online (AJOL)

    admin

    The effect of the methanolic extract of whole plant of B. pilosa on drug ... superoxide dismutase. .... according to the method of Omura and Sato ... 25 % trichloroacetic acid and the precipitate ... in 0.2 M sodium phosphate buffer (pH 8.0), to.

  4. Cancer chemopreventive property of Bidens pilosa methanolic ...

    African Journals Online (AJOL)

    The effect of the methanolic extract of whole plant of B. pilosa on drug metabolizing phase I and II enzymes, antioxidant enzymes, lactate dehydrogenase and lipid peroxidase, anticarcinogenic potential in dimethylbenzathracene induced forestomach and tetradecanoyl acetate promoted skin papillomagenesis was studied ...

  5. Dietary Genistein and Prostate Cancer Chemoprevention

    National Research Council Canada - National Science Library

    Lamartiniere, Coral

    2003-01-01

    .... We have previously demonstrated that genistein is bioavailable to the rat prostate and that life-time exposure to physiological concentrations of genistein suppressed the development of chemically...

  6. Dietary Genistein and Prostate Cancer Chemoprevention

    National Research Council Canada - National Science Library

    Lamartiniere, Coral

    2004-01-01

    .... We have previously demonstrated that genistein is bioavailable to the rat prostate and that life-time exposure to physiological concentrations of genistein suppressed the development of chemically...

  7. Chemoprevention Trial of Selenium and Prostate Cancer

    Science.gov (United States)

    1999-10-01

    mango and papaya o o o o o o o o o 1/4 melon or 1 cup O o o Watermelon and red melon o o o o o o o o o 1 medium slice or 1 cup o o o All other...4. Waller, L.A., Turnbull, B.W., Clark, L.C, Nasca, P. "Examining Spatial Patterns of Disease Incidence Data to Detect Clusters in a Rare Disease: A...Statist. Assoc. Washington, D.C., 1993. 23. Waller, LA., Turnbull, B.W., Clark, L.C., Nasca, P. "Chronic Disease Surveillance and Testing of Clustering of

  8. New cancer cells apoptosis agents: Fluorinated aza-heterocycles

    Science.gov (United States)

    Prima, D. O.; Baev, D. S.; Vorontsova, E. V.; Frolova, T. S.; Bagryanskaya, I. Yu.; Slizhov, Yu. G.; Tolstikova, T. G.; Makarov, A. Yu.; Zibarev, A. V.

    2017-09-01

    Fluorinated benzo-fused 1,3-diazoles, 1,2,3-triazoles, 1,2,5-thia/selenadiazoles and 1,4-diazines were synthesized and tried for cytotoxicity towards the Hep2 (laryngeal epidermoid carcinoma) cells. The diazoles, triazoles and selenadiazoles were cytotoxic with IC50 = 2.2-26.4 µM and induced the cells apoptosis at concentrations C = 1-25 µM. At the same time, they were nontoxic towards normal cells. Due to this, these scaffolds were used in the computer-aided molecular design of new antitumor agents. Particularly, novel 1,2,3-triazole and 1,3-diazole derivatives for the binding site of the PAS domain of the transcription factor HIF were designed and some of them synthesized for further study. Overall, new anticancer agents featuring apoptotic activity are suggested.

  9. Antibody-Based Cancer Therapy : Successful Agents and Novel Approaches

    NARCIS (Netherlands)

    Hendriks, D; Choi, G; de Bruyn, M; Wiersma, V R; Bremer, E; Galluzi, Lorenzo; Vitale, Ilio

    2017-01-01

    Since their discovery, antibodies have been viewed as ideal candidates or "magic bullets" for use in targeted therapy in the fields of cancer, autoimmunity, and chronic inflammatory disorders. A wave of antibody-dedicated research followed, which resulted in the clinical approval of a first

  10. Multi-agent systems: effective approach for cancer care information management.

    Science.gov (United States)

    Mohammadzadeh, Niloofar; Safdari, Reza; Rahimi, Azin

    2013-01-01

    Physicians, in order to study the causes of cancer, detect cancer earlier, prevent or determine the effectiveness of treatment, and specify the reasons for the treatment ineffectiveness, need to access accurate, comprehensive, and timely cancer data. The cancer care environment has become more complex because of the need for coordination and communication among health care professionals with different skills in a variety of roles and the existence of large amounts of data with various formats. The goals of health care systems in such a complex environment are correct health data management, providing appropriate information needs of users to enhance the integrity and quality of health care, timely access to accurate information and reducing medical errors. These roles in new systems with use of agents efficiently perform well. Because of the potential capability of agent systems to solve complex and dynamic health problems, health care system, in order to gain full advantage of E- health, steps must be taken to make use of this technology. Multi-agent systems have effective roles in health service quality improvement especially in telemedicine, emergency situations and management of chronic diseases such as cancer. In the design and implementation of agent based systems, planning items such as information confidentiality and privacy, architecture, communication standards, ethical and legal aspects, identification opportunities and barriers should be considered. It should be noted that usage of agent systems only with a technical view is associated with many problems such as lack of user acceptance. The aim of this commentary is to survey applications, opportunities and barriers of this new artificial intelligence tool for cancer care information as an approach to improve cancer care management.

  11. Copaifera multijuga oleoresin and its constituent diterpene (-)-copalic acid: Genotoxicity and chemoprevention study.

    Science.gov (United States)

    Alves, Jacqueline M; Senedese, Juliana M; Leandro, Luís F; Castro, Pâmela T; Pereira, Daiane E; Carneiro, Luiza J; Ambrósio, Sérgio R; Bastos, Jairo K; Tavares, Denise C

    2017-07-01

    Copaiba oleoresins are used in alternative medicine as anti-inflammatory, antitumoral, and antimicrobial treatments. (-)-Copalic acid (CA) is the major diterpene found in exudates from Copaifera species. We have examined the genotoxicity and the chemopreventive potential of Copaifera multijuga oleoresin (CM) and CA. Genotoxicity assessment was examined with the peripheral blood micronucleus test and the comet assay (male Swiss mouse hepatocytes). In the chemoprevention study, we evaluated the effects of CM and CA on the formation of 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) in male Wistar rat colon. Neither agent caused a significant increase in micronucleus frequency relative to controls, but the highest CM dose tested (400mg/kg b.w.) caused DNA damage in the comet assay. Both agents significantly reduced the frequency of DMH-induced ACF. Both CM and CA suppressed ACF formation and may have a protective effect against colon carcinogenesis. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Association Between hTERT rs2736100 Polymorphism and Sensitivity to Anti-cancer Agents

    Directory of Open Access Journals (Sweden)

    Julie eKim

    2013-08-01

    Full Text Available Background: The rs2736100 single nucleotide polymorphism (SNP is located in the intron 2 of human telomerase reverse transcriptase (hTERT gene. Recent genome-wide association studies (GWAS have consistently supported the strong association between this SNP and risk for multiple cancers. Given the important role of the hTERT gene and this SNP in cancer biology, we hypothesize that rs2736100 may also confer susceptibility to anti-cancer drug sensitivity. In this study we aim to investigate the correlation between the rs2736100 genotype and the responsiveness to anti-cancer agents in the NCI-60 cancer cell panel. Methods and Materials: The hTERT rs2736100 was genotyped in the NCI-60 cancer cell lines. The relative telomere length of each cell line was quantified using real-time PCR. The genotype was then correlated with publically available drug sensitivity data of two agents with telomerase-inhibition activity: Geldanamycin (HSP90 inhibitor and RHPS4/BRACO19 (G-quadruplex stabilizer as well as additional 110 commonly used agents with established mechanism of action. The association between rs2736100 and mutation status of TP53 gene was also tested.Results: The C allele of the SNP was significantly correlated with increased sensitivity to RHPS4/BRACO19 with an additive effect (r=-0.35, p=0.009 but not with Geldanamycin. The same allele was also significantly associated with sensitivity to antimitotic agents compared to other agents (p=0.003. The highest correlation was observed between the SNP and paclitaxel (r=-0.36, p=0.005. The telomere length was neither associated with rs2736100 nor with sensitivity to anti-cancer agents. The C allele of rs2736100 was significantly associated with increased mutation rate in TP53 gene (p=0.004.Conclusion: Our data suggested that the cancer risk allele of hTERT rs2736100 polymorphism may also affect the cancer cell response to both TERT inhibitor and anti-mitotic agents, which might be attributed to the elevated

  13. Impact of nanotechnology in cancer: emphasis on nanochemoprevention.

    Science.gov (United States)

    Siddiqui, Imtiaz A; Adhami, Vaqar M; Chamcheu, Jean Christopher; Mukhtar, Hasan

    2012-01-01

    Since its advent in the field of cancer, nanotechnology has provided researchers with expertise to explore new avenues for diagnosis, prevention, and treatment of the disease. Utilization of nanotechnology has enabled the development of devices in nanometer (nm) sizes which could be designed to encapsulate useful agents that have shown excellent results but otherwise are generally toxic due to the doses intended for extended use. In addition, examples are also available where these devices are easily conjugated with several purposeful moieties for better localization and targeted delivery. We introduced a novel concept in which nanotechnology was utilized for enhancing the outcome of chemoprevention. This idea, which we termed as "nanochemoprevention," was subsequently exploited by several laboratories worldwide and has now become an advancing field in chemoprevention research. This review examines some of the up and coming applications of nanotechnology for cancer detection, imaging, treatment, and prevention. Further, we detail the current and future utilization of nanochemoprevention for prevention and treatment of cancer.

  14. Cannabinoids as therapeutic agents in cancer: current status and future implications

    OpenAIRE

    Chakravarti, Bandana; Ravi, Janani; Ganju, Ramesh K.

    2014-01-01

    The pharmacological importance of cannabinoids has been in study for several years. Cannabinoids comprise of (a) the active compounds of the Cannabis sativa plant, (b) endogenous as well as (c) synthetic cannabinoids. Though cannabinoids are clinically used for anti-palliative effects, recent studies open a promising possibility as anti-cancer agents. They have been shown to possess anti-proliferative and anti-angiogenic effects in vitro as well as in vivo in different cancer models. Cannabin...

  15. Effect of polyphenols on glucose and lactate transport by breast cancer cells.

    Science.gov (United States)

    Martel, F; Guedes, M; Keating, E

    2016-05-01

    One of the cancer molecular hallmarks is a deviant energetic metabolism, known as the Warburg effect, whereby the rate of glucose uptake is significantly increased and a high rate of glycolysis and lactic acid production occurs even when oxygen is present-"aerobic lactatogenesis". Accordingly, GLUT1 and MCT1, which are the main glucose and lactate transporters in cancer cells, respectively, have been proposed as oncogenes and are currently seen as potential therapeutic targets in cancer treatment. Polyphenols, commonly contained in fruits and vegetables, have long been associated with a protective role against cancer. Generally considered as nontoxic, dietary polyphenols are considered ideal chemopreventive and possibly chemotherapeutic agents. Several mechanisms of action of polyphenols in breast cancer cells have been proposed including modulation of intracellular signaling, induction of apoptosis through redox regulation or modulation of epigenetic alterations. Additionally, in vitro studies have shown that several polyphenols act as specific inhibitors of glucose transport in breast cancer cell lines and an association between their anticarcinogenic effect and inhibition of glucose cellular uptake has been described. Also, some polyphenols were found to inhibit lactate transport. Importantly, some polyphenols behave as inhibitors of both glucose and lactate cellular uptake by breast cancer cells and these compounds are thus very interesting in the context of a chemopreventive effect, because they deplete breast cancer cells of their two most important energy suppliers. So, the antimetabolic effect of polyphenols should be regarded as a mechanism of action contributing to their chemopreventive/chemotherapeutic potential in relation to breast cancer.

  16. Identification of an unintended consequence of Nrf2-directed cytoprotection against a key tobacco carcinogen plus a counteracting chemopreventive intervention.

    Science.gov (United States)

    Paonessa, Joseph D; Ding, Yi; Randall, Kristen L; Munday, Rex; Argoti, Dayana; Vouros, Paul; Zhang, Yuesheng

    2011-06-01

    NF-E2-related factor 2 (Nrf2) is a major cytoprotective gene and is a key chemopreventive target against cancer and other diseases. Here we show that Nrf2 faces a dilemma in defense against 4-aminobiphenyl (ABP), a major human bladder carcinogen from tobacco smoke and other environmental sources. Although Nrf2 protected mouse liver against ABP (which is metabolically activated in liver), the bladder level of N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-ABP), the predominant ABP-DNA adduct formed in bladder cells and tissues, was markedly higher in Nrf2(+/+) mice than in Nrf2(-/-) mice after ABP exposure. Notably, Nrf2 protected bladder cells against ABP in vitro. Mechanistic investigations showed that the dichotomous effects of Nrf2 could be explained at least partly by upregulation of UDP-glucuronosyltransferase (UGT). Nrf2 promoted conjugation of ABP with glucuronic acid in the liver, increasing urinary excretion of the conjugate. Although glucuronidation of ABP and its metabolites is a detoxification process, these conjugates, which are excreted in urine, are known to be unstable in acidic urine, leading to delivery of the parent compounds to bladder. Hence, although higher liver UGT activity may protect the liver against ABP, it increases bladder exposure to ABP. These findings raise concerns of potential bladder toxicity when Nrf2-activating chemopreventive agents are used in humans exposed to ABP, especially in smokers. We further show that 5,6-dihydrocyclopenta[c][1,2]-dithiole-3(4H)-thione (CPDT) significantly inhibits dG-C8-ABP formation in bladder cells and tissues but does not seem to significantly modulate ABP-catalyzing UGT in liver. Thus, CPDT exemplifies a counteracting solution to the dilemma posed by Nrf2.

  17. Identification of an unintended consequence of Nrf2-directed cytoprotection against a key tobacco carcinogen plus a counteracting chemopreventive intervention

    Science.gov (United States)

    Paonessa, Joseph D.; Ding, Yi; Randall, Kristen L.; Munday, Rex; Argoti, Dayana; Vouros, Paul; Zhang, Yuesheng

    2011-01-01

    Nrf2 is a major cytoprotective gene and is a key chemopreventive target against cancer and other diseases. Here we show that Nrf2 faces a dilemma in defense against 4-aminobiphenyl (ABP), a major human bladder carcinogen from tobacco smoke and other environmental sources. While Nrf2 protected mouse liver against ABP (which is metabolically activated in liver), the bladder level of N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-ABP), the predominant ABP-DNA adduct formed in bladder cells and tissues, was markedly higher in Nrf2+/+ mice than in Nrf2−/− mice after ABP exposure. Notably, Nrf2 protected bladder cells against ABP in vitro. Mechanistic investigations showed that the dichotomous effects of Nrf2 could be explained at least partly by upregulation of UDP-glucuronosyltransferase (UGT). Nrf2 promoted conjugation of ABP with glucuronic acid in the liver, increasing urinary excretion of the conjugate. While glucuronidation of ABP and its metabolites is a detoxification process, these conjugates, which are excreted in urine, are known to be unstable in acidic urine, leading to delivery of the parent compounds to bladder. Hence, while higher liver UGT activity may protect the liver against ABP it increases bladder exposure to ABP. These findings raise concerns of potential bladder toxicity when Nrf2-activating chemopreventive agents are used in humans exposed to ABP, especially in smokers. We further demonstrate that 5,6-dihydrocyclopenta[c][1,2]-dithiole-3(4H)-thione (CPDT) significantly inhibits dG-C8-ABP formation in bladder cells and tissues, but does not appear to significantly modulate ABP-catalyzing UGT in liver. Thus, CPDT exemplifies a counteracting solution to the dilemma posed by Nrf2. PMID:21487034

  18. Marine-Sourced Anti-Cancer and Cancer Pain Control Agents in Clinical and Late Preclinical Development

    Directory of Open Access Journals (Sweden)

    David J. Newman

    2014-01-01

    Full Text Available The marine habitat has produced a significant number of very potent marine-derived agents that have the potential to inhibit the growth of human tumor cells in vitro and, in a number of cases, in both in vivo murine models and in humans. Although many agents have entered clinical trials in cancer, to date, only Cytarabine, Yondelis® (ET743, Eribulin (a synthetic derivative based on the structure of halichondrin B, and the dolastatin 10 derivative, monomethylauristatin E (MMAE or vedotin as a warhead, have been approved for use in humans (Adcetris®. In this review, we show the compounds derived from marine sources that are currently in clinical trials against cancer. We have included brief discussions of the approved agents, where they are in trials to extend their initial approved activity (a common practice once an agent is approved, and have also included an extensive discussion of the use of auristatin derivatives as warheads, plus an area that has rarely been covered, the use of marine-derived agents to ameliorate the pain from cancers in humans, and to act as an adjuvant in immunological therapies.

  19. [Antitumor and chemopreventive activity of lactoferrin].

    Science.gov (United States)

    Artym, Jolanta

    2006-01-01

    Lactoferrin, an evolutionarily old protein of the transferrin family, is among the proteins constituting the system of innate immunity; its action, however, also extends to the regulation of acquired immunity and other immunological phenomena. The actions of LF, confirmed in numerous in vitro and in vivo models, include participation in iron homeostasis, immunoregulatory properties, anti-inflammatory, anti-tumor, and analgesic actions, regulation of bone metabolism, participation in embryonic development, reproductive functions, and others. LF plays an important role in the normal development of a newborn. The anti-tumor properties of LF were discovered about a decade ago and have been confirmed in many laboratory, preclinical, and clinical studies. The immunomodulatory properties of LF play a major role in its anti-tumor actions. Such actions of LF appeared particularly effective in cancer patients with impaired immunity. The growth of tumors is facilitated by low expressions of MHC and co-stimulatory antigens on tumor cells and the induction of suppressor cells and other inhibitory products by tumors. Enhancement of an anti-tumor immunological response may, therefore, restrict tumor growth. Studies showed that LF elevates the number and increases the activity of T and B lymphocytes and NK cells, stimulates the release of a number of cytokines (IL-1, -6, -8, -18, IFN-gamma, TNF alpha), increases phagocytic activity and cytotoxicity of monocytes/macrophages, accelerates the maturation of T and B cells, and elevates the expression of several types of cellular receptors, such as CD4, zeta chain of the CD3 complex, LFA-1, CD11, ICAM-1, and selectin P. Apart from its immunomodulatory properties, LF exhibits direct anti-tumor actions, such as lytic, pro-apoptotic, anti-proliferative, anti-angiogenic, anti-oxidant activity and the chelation of iron ions. LF also possesses chemo-preventive properties, regulates the activity of phase I and II enzymes participating in the

  20. Norathyriol Suppresses Skin Cancers Induced by Solar Ultraviolet Radiation by Targeting ERK Kinases

    Energy Technology Data Exchange (ETDEWEB)

    Li, Jixia; Malakhova, Margarita; Mottamal, Madhusoodanan; Reddy, Kanamata; Kurinov, Igor; Carper, Andria; Langfald, Alyssa; Oi, Naomi; Kim, Myoung Ok; Zhu, Feng; Sosa, Carlos P.; Zhou, Keyuan; Bode, Ann M.; Dong, Zigang (Cornell); (Guangdong); (UMM)

    2012-06-27

    Ultraviolet (UV) irradiation is the leading factor in the development of skin cancer, prompting great interest in chemopreventive agents for this disease. In this study, we report the discovery of norathyriol, a plant-derived chemopreventive compound identified through an in silico virtual screening of the Chinese Medicine Library. Norathyriol is a metabolite of mangiferin found in mango, Hypericum elegans, and Tripterospermum lanceolatum and is known to have anticancer activity. Mechanistic investigations determined that norathyriol acted as an inhibitor of extracellular signal-regulated kinase (ERK)1/2 activity to attenuate UVB-induced phosphorylation in mitogen-activated protein kinases signaling cascades. We confirmed the direct and specific binding of norathyriol with ERK2 through a cocrystal structural analysis. The xanthone moiety in norathyriol acted as an adenine mimetic to anchor the compound by hydrogen bonds to the hinge region of the protein ATP-binding site on ERK2. Norathyriol inhibited in vitro cell growth in mouse skin epidermal JB6 P+ cells at the level of G{sub 2}-M phase arrest. In mouse skin tumorigenesis assays, norathyriol significantly suppressed solar UV-induced skin carcinogenesis. Further analysis indicated that norathyriol mediates its chemopreventive activity by inhibiting the ERK-dependent activity of transcriptional factors AP-1 and NF-{kappa}B during UV-induced skin carcinogenesis. Taken together, our results identify norathyriol as a safe new chemopreventive agent that is highly effective against development of UV-induced skin cancer.

  1. Assessment of Information to Substantiate a Health Claim on the Prevention of Prostate Cancer by Lignans

    Directory of Open Access Journals (Sweden)

    Juhani Tuominen

    2010-01-01

    Full Text Available Lignans and their in vivo metabolites, especially enterolactone (ENL, have attracted substantial interest as potential chemopreventive agents for prostate cancer. Preclinical and clinical interventions performed with lignan-rich flaxseed that use surrogate biomarkers as endpoints suggest that lignans may attenuate prostate carcinogenesis in individuals with increased risk or with diagnosed cancer. No unequivocal prostate cancer risk reduction has been found for lignans in epidemiological studies, suggesting that lignan concentrations found in populations consuming a regular non-supplemented diet are not chemopreventive in prostate cancer. Presumably, the main obstacles in assessing the efficacy of food lignans is limited knowledge of the serum and tissue lignan concentrations required for the putative prevention. Further clinical studies performed with the purified compounds are required to substantiate a health claim.

  2. Metformin against Cancer Stem Cells through the Modulation of Energy Metabolism: Special Considerations on Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Tae Hun Kim

    2014-01-01

    Full Text Available Ovarian cancer is the most lethal gynecologic malignancy among women worldwide and is presumed to result from the presence of ovarian cancer stem cells. To overcome the limitation of current anticancer agents, another anticancer strategy is necessary to effectively target cancer stem cells in ovarian cancer. In many types of malignancies, including ovarian cancer, metformin, one of the most popular antidiabetic drugs, has been demonstrated to exhibit chemopreventive and anticancer efficacy with respect to incidence and overall survival rates. Thus, the metabolic reprogramming of cancer and cancer stem cells driven by genetic alterations during carcinogenesis and cancer progression could be therapeutically targeted. In this review, the potential efficacy and anticancer mechanisms of metformin against ovarian cancer stem cells will be discussed.

  3. Fuzzy-probabilistic multi agent system for breast cancer risk assessment and insurance premium assignment.

    Science.gov (United States)

    Tatari, Farzaneh; Akbarzadeh-T, Mohammad-R; Sabahi, Ahmad

    2012-12-01

    In this paper, we present an agent-based system for distributed risk assessment of breast cancer development employing fuzzy and probabilistic computing. The proposed fuzzy multi agent system consists of multiple fuzzy agents that benefit from fuzzy set theory to demonstrate their soft information (linguistic information). Fuzzy risk assessment is quantified by two linguistic variables of high and low. Through fuzzy computations, the multi agent system computes the fuzzy probabilities of breast cancer development based on various risk factors. By such ranking of high risk and low risk fuzzy probabilities, the multi agent system (MAS) decides whether the risk of breast cancer development is high or low. This information is then fed into an insurance premium adjuster in order to provide preventive decision making as well as to make appropriate adjustment of insurance premium and risk. This final step of insurance analysis also provides a numeric measure to demonstrate the utility of the approach. Furthermore, actual data are gathered from two hospitals in Mashhad during 1 year. The results are then compared with a fuzzy distributed approach. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Use of Incretin Agents and Risk of Pancreatic Cancer : A Population-Based Cohort Study

    NARCIS (Netherlands)

    Knapen, Lotte M; van Dalem, Judith; Keulemans, Yolande C; van Erp, Nielka P; Bazelier, Marloes T; De Bruin, Marie L; Leufkens, Hubert G M; Croes, Sander; Neef, Cees; de Vries, Frank; Driessen, Johanna H M

    Aim To investigate the association between the use of incretin agents and the risk of pancreatic cancer. Methods A retrospective population-based cohort study, using data from the Clinical Practice Research Datalink, 2007–2012, was conducted. Patients (n = 182 428) with at least one non-insulin

  5. Use of incretin agents and risk of pancreatic cancer: a population-based cohort study

    NARCIS (Netherlands)

    Knapen, L.M.; Dalem, J. van; Keulemans, Y.C.; Erp, N. van; Bazelier, M.T.; Bruin, M.L. De; Leufkens, H.G.; Croes, S.; Neef, C.; Vries, F de; Driessen, J.H.

    2016-01-01

    AIM: To investigate the association between the use of incretin agents and the risk of pancreatic cancer. METHODS: A retrospective population-based cohort study, using data from the Clinical Practice Research Datalink, 2007-2012, was conducted. Patients (n = 182 428) with at least one non-insulin

  6. Systematic review of anti-inflammatory agents for the management of oral mucositis in cancer patients

    NARCIS (Netherlands)

    Nicolatou-Galitis, Ourania; Sarri, Triantafyllia; Bowen, Joanne; Di Palma, Mario; Kouloulias, Vassilios E.; Niscola, Pasquale; Riesenbeck, Dorothea; Stokman, Monique; Tissing, Wim; Yeoh, Eric; Elad, Sharon; Lalla, Rajesh V.

    2013-01-01

    Purpose The aim of this project was to review the available literature and define clinical practice guidelines for the use of anti-inflammatory agents for the prevention and treatment of oral mucositis in cancer patients. Materials and methods A systematic review was conducted by the Mucositis Study

  7. Sea Cucumbers Metabolites as Potent Anti-Cancer Agents

    Directory of Open Access Journals (Sweden)

    Naveena B. Janakiram

    2015-05-01

    Full Text Available Sea cucumbers and their extracts have gained immense popularity and interest among researchers and nutritionists due to their nutritive value, potential health benefits, and use in the treatment of chronic inflammatory diseases. Many areas of the world use sea cucumbers in traditional foods and folk medicine. Though the actual components and their specific functions still remain to be investigated, most sea cucumber extracts are being studied for their anti-inflammatory functions, immunostimulatory properties, and for cancer prevention and treatment. There is large scope for the discovery of additional bioactive, valuable compounds from this natural source. Sea cucumber extracts contain unique components, such as modified triterpene glycosides, sulfated polysaccharides, glycosphingolipids, and esterified phospholipids. Frondanol A5, an isopropyl alcohol/water extract of the enzymatically hydrolyzed epithelia of the edible North Atlantic sea cucumber, Cucumaria frondosa, contains monosulfated triterpenoid glycoside Frondoside A, the disulfated glycoside Frondoside B, the trisulfated glycoside Frondoside C, 12-methyltetradecanoic acid, eicosapentaenoic acid, and fucosylated chondroitin sulfate. We have extensively studied the efficacy of this extract in preventing colon cancer in rodent models. In this review, we discuss the anti-inflammatory, immunostimulatory, and anti-tumor properties of sea cucumber extracts.

  8. Evolving perspectives of the role of novel agents in androgen-independent prostate cancer

    Directory of Open Access Journals (Sweden)

    Sujith Kalmadi

    2008-01-01

    Full Text Available Metastatic androgen-independent prostate cancer presents an intriguing clinical challenge, with a subtle interaction between hormone-responsive and refractory tumor cell elements. The treatment of advanced prostate carcinoma, which had remained stagnant for several decades following the understanding of the link between androgenic stimulation and carcinogenesis, has now started to make steady headway with chemotherapy and targeted approaches. Metastatic prostate cancer is almost always treated with initial androgen deprivation, in various forms. However, despite such treatment androgen-independent prostate cancer cells eventually emerge and progress to threaten life. The therapeutic objectives for treatment of metastatic prostate cancer are to maintain the quality of life and prolong survival. The out-dated nihilistic dogma of deferring chemotherapy until the most advanced stages in advanced prostate cancer is now falling by the wayside with the development of newer effective, tolerable agents.

  9. A critical review of the epidemiology of Agent Orange/TCDD and prostate cancer.

    Science.gov (United States)

    Chang, Ellen T; Boffetta, Paolo; Adami, Hans-Olov; Cole, Philip; Mandel, Jack S

    2014-10-01

    To inform risk assessment and regulatory decision-making, the relationship between 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and prostate cancer requires clarification. This article systematically and critically reviews the epidemiologic evidence on the association between exposure to TCDD or Agent Orange, a TCDD-contaminated herbicide used during the Vietnam War, and prostate cancer risk. Articles evaluated include 11 studies of three cohorts, four case-control or cross-sectional studies, and three case-only studies of military veterans with information on estimated Agent Orange or TCDD exposure; 13 studies of seven cohorts, one case-control study, and eight proportionate morbidity or mortality studies of Vietnam veterans without information on Agent Orange exposure; 11 cohort studies of workers with occupational exposure to TCDD; and two studies of one community cohort with environmental exposure to TCDD. The most informative studies, including those of Vietnam veterans involved in Agent Orange spraying or other handling, herbicide manufacturing or spraying workers with occupational TCDD exposure, and community members exposed to TCDD through an industrial accident, consistently reported no significant increase in prostate cancer incidence or mortality. Only some potentially confounded studies of Vietnam veterans compared with the general population, studies with unreliable estimates of Agent Orange exposure, and analyses of selected subgroups of Vietnam veterans reported positive associations. Overall, epidemiologic research offers no consistent or convincing evidence of a causal relationship between exposure to Agent Orange or TCDD and prostate cancer. More accurate exposure assessment is needed in large epidemiologic studies to rule out a causal association more conclusively.

  10. Proteomics of cancer cell lines resistant to microtubule-stabilizing agents

    DEFF Research Database (Denmark)

    Albrethsen, Jakob; Angeletti, Ruth H; Horwitz, Susan Band

    2014-01-01

    resistance to the class of MIAs known as microtubule-stabilizing agents (MSA). The human lung cancer cell line A549 was compared with two drug-resistant daughter cell lines, a taxol-resistant cell line (AT12) and an epothilone B (EpoB)-resistant cell line (EpoB40). The ovarian cancer cell line Hey......Despite the clinical success of microtubule-interacting agents (MIA), a significant challenge for oncologists is the inability to predict the response of individual patients with cancer to these drugs. In the present study, six cell lines were compared by 2D DIGE proteomics to investigate cellular...... increased in EpoB- and ixabepilone-resistant cells and its suppression caused an increase in drug sensitivity in both drug-sensitive and -resistant Hey cells. Furthermore, the growth medium from resistant Hey cells contained higher levels of galectin-1, suggesting that galectin-1 could play a role...

  11. Clinical trials of antioxidants as cancer prevention agents: past, present, and future.

    Science.gov (United States)

    Goodman, Michael; Bostick, Roberd M; Kucuk, Omer; Jones, Dean P

    2011-09-01

    The purpose of this review is to summarize the most important human clinical trials of antioxidants as cancer prevention agents conducted to date, provide an overview of currently ongoing studies, and discuss future steps needed to advance research in this field. To date there have been several large (at least 7000 participants) trials testing the efficacy of antioxidant supplements in preventing cancer. The specific agents (diet-derived direct antioxidants and essential components of antioxidant enzymes) tested in those trials included β-carotene, vitamin E, vitamin C, selenium, retinol, zinc, riboflavin, and molybdenum. None of the completed trials produced convincing evidence to justify the use of traditional antioxidant-related vitamins or minerals for cancer prevention. Our search of ongoing trials identified six projects at various stages of completion. Five of those six trials use selenium as the intervention of interest delivered either alone or in combination with other agents. The lack of success to date can be explained by a variety of factors that need to be considered in the next generation research. These factors include lack of good biological rationale for selecting specific agents of interest; limited number of agents tested to date; use of pharmacological, rather than dietary, doses; and insufficient duration of intervention and follow-up. The latter consideration underscores the need for alternative endpoints that are associated with increased risk of neoplasia (i.e., biomarkers of risk), but are detectable prior to tumor occurrence. Although dietary antioxidants are a large and diverse group of compounds, only a small proportion of candidate agents have been tested. In summary, the strategy of focusing on large high-budget studies using cancer incidence as the endpoint and testing a relatively limited number of antioxidant agents has been largely unsuccessful. This lack of success in previous trials should not preclude us from seeking novel

  12. STUDY ON STUDENTS’ AWARENESS CONCERNING ENVIRONMENTAL AND OCCUPATIONAL HAZARDOUS AGENTS OF CANCER RISK AND PREVENTION METHODS

    Directory of Open Access Journals (Sweden)

    Antonina Cebulska-Wasilewska

    2010-09-01

    Full Text Available Background. The aim of our study was to assess the level of awareness and knowledge on environmental and occupational risk of cancer and its prevention among Polish students. We were interested also in their sources of knowledge. Methods. Survey, using the questionnaire, was conducted among 1080 respondents, who are or probably will be in their future work, exposed to harmful agents, due to study profile. Results. Students rated their knowledge on environmental and occupational cancer agents and cancer prevention mostly as limited (over 77%. Participation in “Safety Work and Environment” courses did not differentiate their level of cancer risk awareness. 901 students (84% responded to question about specific substances, which may cause cancer. Almost 2% of students indicated none from 10 given agents as carcinogenic. About 34% of respondents pointed all given agents, 39% pointed on 8–9 of them, 5–7 agents 13.2% of surveyed and 9% of them indicated on 1–4 agents. Students were aware of carcinogenic features of radiation, asbestos, cigarettes smoking (93.2–93.8%, benzene, benzo[?]pirene and pesticides (79,2 –83,6%. Less of them declared carcinogenic features of PAHs (75.4%, heavy metals (73.9%, electromagnetic field (64.8% and infections (60.8%. Only 48% of respondents specified possible lowering of the cancer by risk intervention practices. Medical and engineering profile, as well as attendance in courses covering the issues of health safety at work or environment (SWE significantly decreased percentage of respondents who didn’t specified any procedure (but it was still high: 48–62%. Conclusion. Our results demonstrate that most students, only to some extent, are aware of the most well known cancer-causing substances occurrence. Their knowledge is mostly limited and they do not know prevention procedures and ways to lower or eliminate the risk. Therefore the modernization of educational programs and development of more efficient

  13. Hedgehog Signaling Inhibitors as Anti-Cancer Agents in Osteosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Ram Kumar, Ram Mohan, E-mail: rkumar@research.balgrist.ch; Fuchs, Bruno [Laboratory for Orthopaedic Research, Balgrist University Hospital, Sarcoma Center-UZH University of Zurich, Zurich 8008 (Switzerland)

    2015-05-13

    Osteosarcoma is a rare type of cancer associated with a poor clinical outcome. Even though the pathologic characteristics of OS are well established, much remains to be understood, particularly at the molecular signaling level. The molecular mechanisms of osteosarcoma progression and metastases have not yet been fully elucidated and several evolutionary signaling pathways have been found to be linked with osteosarcoma pathogenesis, especially the hedgehog signaling (Hh) pathway. The present review will outline the importance and targeting the hedgehog signaling (Hh) pathway in osteosarcoma tumor biology. Available data also suggest that aberrant Hh signaling has pro-migratory effects and leads to the development of osteoblastic osteosarcoma. Activation of Hh signaling has been observed in osteosarcoma cell lines and also in primary human osteosarcoma specimens. Emerging data suggests that interference with Hh signal transduction by inhibitors may reduce osteosarcoma cell proliferation and tumor growth thereby preventing osteosarcomagenesis. From this perspective, we outline the current state of Hh pathway inhibitors in osteosarcoma. In summary, targeting Hh signaling by inhibitors promise to increase the efficacy of osteosarcoma treatment and improve patient outcome.

  14. Thiol-reducing agents prevent sulforaphane-induced growth inhibition in ovarian cancer cells.

    Science.gov (United States)

    Kim, Seung Cheol; Choi, Boyun; Kwon, Youngjoo

    2017-01-01

    The inhibitory potential of sulforaphane against cancer has been suggested for different types of cancer, including ovarian cancer. We examined whether this effect is mediated by mitogen-activated protein kinase (MAPK) and reactive oxygen species (ROS), important signaling molecules related to cell survival and proliferation, in ovarian cancer cells. Sulforaphane at a concentration of 10 μM effectively inhibited the growth of cancer cells. Use of specific inhibitors revealed that activation of MAPK pathways by sulforaphane is unlikely to mediate sulforaphane-induced growth inhibition. Sulforaphane did not generate significant levels of intracellular ROS. Pretreatment with thiol reducers, but not ROS scavengers, prevented sulforaphane-induced growth inhibition. Furthermore, diamide, a thiol-oxidizing agent, enhanced both growth inhibition and cell death induced by sulforaphane, suggesting that the effect of sulforaphane on cell growth may be related to oxidation of protein thiols or change in cellular redox status. Our data indicate that supplementation with thiol-reducing agents should be avoided when sulforaphane is used to treat cancer.

  15. HIGH PREVALENCE OF AGENT ORANGE EXPOSURE AMONG THYROID CANCER PATIENTS IN THE NATIONAL VA HEALTHCARE SYSTEM.

    Science.gov (United States)

    Le, Karen T; Sawicki, Mark P; Wang, Marilene B; Hershman, Jerome M; Leung, Angela M

    2016-06-01

    Thyroid cancer is the most common endocrine malignancy and the most rapidly increasing cancer in the U.S. Little is known regarding the epidemiology and characteristics of patients with thyroid cancer within the national Veterans Health Administration (VHA) integrated healthcare system. The aim of this study was to further understand the characteristics of thyroid cancer patients in the VHA population, particularly in relation to Agent Orange exposure. This is a descriptive analysis of the VA (Veterans Affairs) Corporate Data Warehouse database from all U.S. VHA healthcare sites from October1, 1999, to December 31, 2013. Information was extracted for all thyroid cancer patients based on International Classification of Diseases-ninth revision diagnosis codes; histologic subtypes of thyroid cancer were not available. There were 19,592 patients (86% men, 76% white, 58% married, 42% Vietnam-era Veteran) in the VHA system with a diagnosis of thyroid cancer within this 14-year study period. The gender-stratified prevalence rates of thyroid cancer among the Veteran population during the study period were 1:1,114 (women) and 1:1,023 (men), which were lower for women but similar for men, when compared to the U.S. general population in 2011 (1:350 for women and 1:1,219 for men). There was a significantly higher proportion of self-reported Agent Orange exposure among thyroid cancer patients (10.0%), compared to the general VHA population (6.2%) (PAgent Orange exposure compared to the overall national VA patient population. T4 = thyroxine TCDD = 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin TSH = thyroid-stimulating hormone VA = Veterans Affairs VHA = Veterans Health Administration.

  16. Anti-tumor agent celecoxib activity towards SP-C1 tongue cancer cells invasion (in vitro

    Directory of Open Access Journals (Sweden)

    Harun Achmad

    2011-03-01

    Full Text Available Invasion is a characteristic of the occurrence of cancer and indicates the cancer cells' capability to destroy and degrade the border between the epithet and basal membrane to further spread into the surrounding extra-cellular matrix. The purpose of this research was to find the existence of impediment at the SP-C1 tongue cancer cell using celecoxib chemopreventive medication. The SP-C1 tongue cancer cells were treated in vitro using celecoxib medication as a research subject at the following concentrations 5, 10, 25, 50, 75, 100, 125%; and 0 as control group (only DMEM growth medium treatment. Pure experimental testing was carried out for 24 and 48 hours, with observation and calculation of an average number of SP-C1 tongue cancer cells. The data collected were analyzed using the ANOVA test with Newman Keuls paired range test or t-test. Research results indicated that the average number of SP-C1 tongue cancer cells invasion after administration of celecoxib medication based on administration concentration and time statistically yielded significant results. The ANOVA test results were statistically significant, that is, average occurrence of the number of SP-C1 tongue cancer cells due to the use of celecoxib at certain concentrations compared to that without celecoxib was different. At celecoxib of zero (control concentration was 24.4 with celecoxib concentration starting at 5 up to 125% experienced a decline from its average 11 to become 2.3. The conclusion of the research was that the greater the celecoxib concentration administered, the greater the effect on the impediment of SP-C1 tongue cancer cell invasion.

  17. Study of anti-cancer effects of chemotherapeutic agents and radiotherapy in breast cancer patients using fluorescence spectroscopy

    Science.gov (United States)

    Chithra, K.; Vijayaraghavan, S.; Prakasarao, Aruna; Singaravelu, Ganesan

    2017-02-01

    The analysis of the variations in the spectroscopic patterns of the key bio molecules using Native fluorescence spectroscopy, without exogenous labels, has emerged as a new trend in the characterization of the Physiological State and the Discrimination of Pathological from normal conditions of cells and tissues as the relative concentration of these bio-molecules serve as markers in evaluating the presence of cancer in the body. The aim of this unique study is to use these features of Optical spectroscopy in monitoring the behavior of cells to treatment and thus to evaluate the response to Chemotherapeutic agents and Radiation in Breast Cancer Patients. The results of the study conducted using NFS of Human blood plasma of biopsy proved Breast Cancer patients undergoing treatment are promising, enhancing the scope of Native fluorescence Spectroscopy emerging as a promising technology in the evaluation of Therapeutic Response in Breast Cancer Patients.

  18. Inhibition of Sphingolipid Metabolism Enhances Resveratrol Chemotherapy in Human Gastric Cancer Cells

    OpenAIRE

    Shin, Kyong-Oh; Park, Nam-Young; Seo, Cho-Hee; Hong, Seon-Pyo; Oh, Ki-Wan; Hong, Jin-Tae; Han, Sang-Kil; Lee, Yong-Moon

    2012-01-01

    Resveratrol, a chemopreventive agent, is rapidly metabolized in the intestine and liver via glucuronidation. Thus, the pharmacokinetics of resveratrol limits its efficacy. To improve efficacy, the activity of resveratrol was investigated in the context of sphingolipid metabolism in human gastric cancer cells. Diverse sphingolipid metabolites, including dihydroceramides (DHCer), were tested for their ability to induce resveratrol cytotoxicity. Exposure to resveratrol (100 ?M) for 24 hr induced...

  19. Does Variation in Either Age at Start of Therapy or Duration of Therapy Make Chemoprevention with Finasteride Cost-Effective?

    Science.gov (United States)

    Stewart, Suzanne Biehn; Scales, Charles D.; Moul, Judd W.; Reed, Shelby D.

    2013-01-01

    Background Incremental cost-effectiveness ratios (ICER) of finasteride for prostate cancer prevention are consistent with estimates beyond $100,000 per quality-adjusted life-year (QALY). The majority of these analyses are based on chemoprevention starting in men aged 50–55yrs. We sought to evaluate the impact of varying both age at commencement of therapy and length of therapy on the cost-effectiveness of finasteride. Methods A probabilistic Markov model was designed to estimate lifetime prostate health related costs and quality-adjusted survival for men receiving or not receiving chemoprevention with finasteride. ICERs across scenarios varying age at start of therapy and duration of chemoprevention were compared. Results The ICER for men starting chemoprevention at age 50 and continuing to age 75 was $88,800 per QALY when assuming finasteride causes a constant risk reduction across all tumor grades (base case 1) and $142,300 per when assuming a differential treatment effect according to Gleason score (base case 2). When starting age is increased, the ICERs trend downward and nadir at 65 years to $64,700 per QALY (base case 1) and $118,600 per QALY (base case 2). Altering duration of therapy had minimal impact. Patient-level experiences with finasteride and BPH significantly influenced the cost-effectiveness of chemoprevention. Conclusion Initiating chemoprevention at ages when prostate cancer incidence is higher improves its cost-effectiveness profile. Only when assuming a constant risk reduction for all tumor grades, did finasteride fall below $100,000 per QALY, but this finding was not upheld when accounting for side effects associated with the drug. PMID:22777393

  20. Preclinical therapeutic potential of a nitrosylating agent in the treatment of ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Shailendra Giri

    Full Text Available This study examines the role of s-nitrosylation in the growth of ovarian cancer using cell culture based and in vivo approaches. Using the nitrosylating agent, S-nitrosoglutathione (GSNO, a physiological nitric oxide molecule, we show that GSNO treatment inhibited proliferation of chemoresponsive and chemoresistant ovarian cancer cell lines (A2780, C200, SKVO3, ID8, OVCAR3, OVCAR4, OVCAR5, OVCAR7, OVCAR8, OVCAR10, PE01 and PE04 in a dose dependent manner. GSNO treatment abrogated growth factor (HB-EGF induced signal transduction including phosphorylation of Akt, p42/44 and STAT3, which are known to play critical roles in ovarian cancer growth and progression. To examine the therapeutic potential of GSNO in vivo, nude mice bearing intra-peritoneal xenografts of human A2780 ovarian carcinoma cell line (2 × 10(6 were orally administered GSNO at the dose of 1 mg/kg body weight. Daily oral administration of GSNO significantly attenuated tumor mass (p<0.001 in the peritoneal cavity compared to vehicle (phosphate buffered saline treated group at 4 weeks. GSNO also potentiated cisplatin mediated tumor toxicity in an A2780 ovarian carcinoma nude mouse model. GSNO's nitrosylating ability was reflected in the induced nitrosylation of various known proteins including NFκB p65, Akt and EGFR. As a novel finding, we observed that GSNO also induced nitrosylation with inverse relationship at tyrosine 705 phosphorylation of STAT3, an established player in chemoresistance and cell proliferation in ovarian cancer and in cancer in general. Overall, our study underlines the significance of S-nitrosylation of key cancer promoting proteins in modulating ovarian cancer and proposes the therapeutic potential of nitrosylating agents (like GSNO for the treatment of ovarian cancer alone or in combination with chemotherapeutic drugs.

  1. Association between Agent Orange exposure and nonmelanotic invasive skin cancer: a pilot study.

    Science.gov (United States)

    Clemens, Mark W; Kochuba, Andrew L; Carter, Mary Ella; Han, Kevin; Liu, Jun; Evans, Karen

    2014-02-01

    Agent Orange, or 2,3,7,8-tetrachlorodibenzodioxin, has been shown to cause indirect DNA damage, producing malignancies. However, its connection to nonmelanotic invasive skin cancer is unclear. This study investigated whether 2,3,7,8-tetrachlorodibenzodioxin exposure increases the incidence of this cancer. The authors retrospectively reviewed the medical records of 100 consecutive male patients with Fitzpatrick skin types I through IV who enrolled in the Agent Orange registry at the Veterans Affairs Hospital of Washington, D.C., between August of 2009 and January of 2010. The study population's mean age was 65.7 years (range, 56 to 80 years). 2,3,7,8-Tetrachlorodibenzodioxin exposure included living or working in contaminated areas (56 percent), actively spraying it (30 percent), or traveling in contaminated areas (14 percent). Fifty-one percent of patients had nonmelanotic invasive skin cancer; 43 percent had chloracne; and 26 percent had other malignancies, such as prostate (14 percent), colon (3 percent), or bladder cancer (2 percent). The nonmelanotic invasive skin cancer incidence rate in the study population (51 percent) was significantly higher than the national age-matched incidence rate (23.8 percent; p < 0.001). High Fitzpatrick skin type score (p = 0.010) and dark eye color (p = 0.036) were associated with a decreased incidence of the cancer. Exposure by means of active spraying (73 percent versus 67 percent; p = 0.003) and presence of chloracne (81 percent versus 28 percent; p < 0.001) were associated with increased nonmelanotic invasive skin cancer incidence rates. 2,3,7,8-Tetrachlorodibenzodioxin exposure appears to be associated with the development of nonmelanotic invasive skin cancer. Further studies are warranted to determine the relative risk within this patient population and to determine appropriate management strategies. Risk, II.

  2. G-quadruplex oligonucleotide AS1411 as a cancer-targeting agent: Uses and mechanisms.

    Science.gov (United States)

    Bates, Paula J; Reyes-Reyes, Elsa M; Malik, Mohammad T; Murphy, Emily M; O'Toole, Martin G; Trent, John O

    2017-05-01

    AS1411 is a 26-mer G-rich DNA oligonucleotide that forms a variety of G-quadruplex structures. It was identified based on its cancer-selective antiproliferative activity and subsequently determined to be an aptamer to nucleolin, a multifunctional protein that preferentially binds quadruplex nucleic acids and which is present at high levels on the surface of cancer cells. AS1411 has exceptionally efficient cellular internalization compared to non-quadruplex DNA sequences. Recent developments related to AS1411 will be examined, with a focus on its use for targeted delivery of therapeutic and imaging agents. Numerous research groups have used AS1411 as a targeting agent to deliver nanoparticles, oligonucleotides, and small molecules into cancer cells. Studies in animal models have demonstrated that AS1411-linked materials can accumulate selectively in tumors following systemic administration. The mechanism underlying the cancer-targeting ability of AS1411 is not completely understood, but recent studies suggest a model that involves: (1) initial uptake by macropinocytosis, a form of endocytosis prevalent in cancer cells; (2) stimulation of macropinocytosis by a nucleolin-dependent mechanism resulting in further uptake; and (3) disruption of nucleolin-mediated trafficking and efflux leading to cargoes becoming trapped inside cancer cells. Human trials have indicated that AS1411 is safe and can induce durable remissions in a few patients, but new strategies are needed to maximize its clinical impact. A better understanding of the mechanisms by which AS1411 targets and kills cancer cells may hasten the development of promising technologies using AS1411-linked nanoparticles or conjugates for cancer-targeted therapy and imaging. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio. Copyright © 2016. Published by Elsevier B.V.

  3. Pomegranate exerts chemoprevention of experimentally induced mammary tumorigenesis by suppression of cell proliferation and induction of apoptosis

    Science.gov (United States)

    Bishayee, Anupam; Mandal, Animesh; Bhattacharyya, Piyali; Bhatia, Deepak

    2016-01-01

    abstract Breast cancer is the second leading cause of cancer-related death in women in the United States and discovery and development of safe chemopreventive drugs is urgently needed. The fruit pomegranate (Punica granatum) is gaining importance because of its various health benefits. This study was initiated to investigate chemopreventive potential of a pomegranate emulsion (PE) against 7,12-dimethylbenz(a)anthracene (DMBA) rat mammary carcinogenesis. The animals were orally administered with PE (0.2–5.0 g/kg), starting 2 wk before and 16 wk following DMBA treatment. PE exhibited a striking reduction of DMBA-induced mammary tumor incidence, total tumor burden, and reversed histopathological changes. PE dose-dependently suppressed cell proliferation and induced apoptosis in mammary tumors. Immunohistochemical studies showed that PE increased intratumor Bax, decreased Bcl2 and manifested a proapoptotic shift in Bax/Bcl2 ratio. In addition, our gene expression study showed PE-mediated upregulation of Bad, caspase-3, caspase-7, caspase-9, poly (ADP ribose) polymerase and cytochrome c in mammary tumors. Thus, PE exerts chemoprevention of mammary carcinogenesis by suppressing cell proliferation and inducing apoptosis mediated through upregulation of Bax and downregulation of Bcl2 in concert with caspase cascades. Pomegranate bioactive phytoconstituents could be developed as a chemopreventive drug to reduce the risk of breast cancer. PMID:26699876

  4. Role of infectious agents in the carcinogenesis of brain and head and neck cancers

    Directory of Open Access Journals (Sweden)

    Alibek Kenneth

    2013-02-01

    Full Text Available Abstract This review concentrates on tumours that are anatomically localised in head and neck regions. Brain cancers and head and neck cancers together account for more than 873,000 cases annually worldwide, with an increasing incidence each year. With poor survival rates at late stages, brain and head and neck cancers represent serious conditions. Carcinogenesis is a multi-step process and the role of infectious agents in this progression has not been fully identified. A major problem with such research is that the role of many infectious agents may be underestimated due to the lack of or inconsistency in experimental data obtained globally. In the case of brain cancer, no infection has been accepted as directly oncogenic, although a number of viruses and parasites are associated with the malignancy. Our analysis of the literature showed the presence of human cytomegalovirus (HCMV in distinct types of brain tumour, namely glioblastoma multiforme (GBM and medulloblastoma. In particular, there are reports of viral protein in up to 100% of GBM specimens. Several epidemiological studies reported associations of brain cancer and toxoplasmosis seropositivity. In head and neck cancers, there is a distinct correlation between Epstein-Barr virus (EBV and nasopharyngeal carcinoma (NPC. Considering that almost every undifferentiated NPC is EBV-positive, virus titer levels can be measured to screen high-risk populations. In addition there is an apparent association between human papilloma virus (HPV and head and neck squamous cell carcinoma (HNSCC; specifically, 26% of HNSCCs are positive for HPV. HPV type 16 was the most common type detected in HNSCCs (90% and its dominance is even greater than that reported in cervical carcinoma. Although there are many studies showing an association of infectious agents with cancer, with various levels of involvement and either a direct or indirect causative effect, there is a scarcity of articles covering the role of

  5. Preparation and evaluation of tributyrin emulsion as a potent anti-cancer agent against melanoma.

    Science.gov (United States)

    Kang, Sung Nam; Lee, Eunmyong; Lee, Mi-Kyung; Lim, Soo-Jeong

    2011-02-01

    Histone deacetylase inhibitors such as butyrate are known to exhibit anti-cancer activities in a wide range of cancer including melanoma. In spite of these potencies, butyrate is not practically used for cancer treatment due to its rapid metabolism and very short plasma half-life. Tributyrin, a triglyceride analog of butyrate, can act as a pro-drug of butyrate after being cleaved by intracellular enzymes. The present study sought to investigate a possibility to develop tributyrin emulsion as a potent anti-cancer agent against melanoma. Mixture of Tween80 and 1, 2-dimyristoyl-sn-glycero-3-phosphocholine as a surfactant to disperse tributyrin produced homogeneous emulsions with nanometer sizes, even without a harsh homogenization procedure. Tributyrin emulsion was more potent than butyrate in inhibiting the growth of B16-F10 melanoma cells. Accumulation of cells at sub G(0)/G(1) phase and the DNA fragmentation induced by tributyrin emulsion treatment revealed that tributyrin emulsion inhibited the growth of B16-F10 cells by inducing apoptosis. Treatment with tributyrin emulsion suppressed the colony formation of melanoma cells in a dose-dependent manner. Furthermore, after intraperitoneal administration into mice, tributyrin emulsion inhibited the formation of tumor colonies in the lung following intravenous injection of melanoma cells. Taken together, our data suggests that tributyrin emulsion may be developed as a potent anti-cancer agent against melanoma.

  6. Cancer Preventive Potential of Kimchi Lactic Acid Bacteria (Weissella cibaria, Lactobacillus plantarum).

    Science.gov (United States)

    Kwak, Shin-Hye; Cho, Young-Mi; Noh, Geon-Min; Om, Ae-Son

    2014-12-01

    The number of death due to cancer has been increasing in Korea. Chemotherapy is known to cause side effects because it damages not only cancerous cells but healthy cells. Recently, attention has focused on food-derived chemopreventive and anti-tumor agents or formulations with fewer side effects. Kimchi, most popular and widely consumed in Korea, contains high levels of lactic acid bacteria and has been shown to possess chemopreventive effects. This review focuses on Weissella cibaria and Lactobacillus plantarum, the representatives of kimchi lactic acid bacteria, in terms of their abilities to prevent cancer. Further studies are needed to understand the mechanisms by which lactic acid bacteria in kimchi prevent carcinogenic processes and improve immune functions.

  7. Chemosensitization of Breast Cancer Cells to Chemotherapeutic Agents by 3,3’-Diindolylmethane (DIM)

    Science.gov (United States)

    2007-08-01

    isoflavone genistein, a natural inhibitor of NF-κB, in BXPC-3 pancreatic cancer cell line. Pancreas, in press 2004. 25. Arlt A, Gehrz A, Muerkoster S, et...effect of chemotherapeutic agents is potentiated by soy isoflavone genistein, a natural inhibitor of NF-kB, in BXPC-3 pancreatic cancer cell line...manufacturer’s protocols. cDNA for each sample was synthesized using a Superscript cDNA Synthesis kit (Invitrogen) and a T7-(dT)24 primer instead of the oligo

  8. Prostate cancer control and survival in Vietnam veterans exposed to Agent Orange.

    Science.gov (United States)

    Everly, Lydia; Merrick, Gregory S; Allen, Zachariah A; Butler, Wayne M; Wallner, Kent; Lief, Jonathan H; Galbreath, Robert W; Adamovich, Edward

    2009-01-01

    In this study, we evaluated the impact of Agent Orange exposure on survival in Vietnam Veterans undergoing prostate brachytherapy. From May 1995 to January 2005, 81 Vietnam veterans (29 with Agent Orange exposure and 52 without) and 433 nonveterans of comparable age (mean age, 58 years) underwent prostate brachytherapy. The mean follow-up was 5.0 years. Biochemical progression-free survival (bPFS) was defined as a prostate-specific antigen (PSA)Agent Orange-exposed men were least likely to remain biochemically controlled (89.5%, 100%, and 97.2% in Agent Orange-exposed, nonexposed veterans, and nonveterans, respectively, p=0.012). No significant differences in cause-specific (CSS) (p=0.832) or overall survival (OS) (p=0.363) were discerned. In multivariate analysis, CSS was best predicted by Gleason Score and day 0 D(90), whereas Gleason Score, % positive biopsies, and D(90) predicted for bPFS. None of the evaluated parameters predicted for OS, however, a trend was identified for better OS in younger patients and those with a higher D(90). In addition, Agent Orange exposure did not predict for any of the survival parameters. To date, 22 patients have died (metastatic prostate cancer two, second malignancies nine, cardiovascular disease eight, trauma two, and pulmonary one). In this cohort of prostate brachytherapy patients, Agent Orange exposure did not statistically impact survival in multivariate analysis.

  9. Modern dose-finding designs for cancer phase I trials drug combinations and molecularly targeted agents

    CERN Document Server

    Hirakawa, Akihiro; Daimon, Takashi; Matsui, Shigeyuki

    2018-01-01

    This book deals with advanced methods for adaptive phase I dose-finding clinical trials for combination of two agents and molecularly targeted agents (MTAs) in oncology. It provides not only methodological aspects of the dose-finding methods, but also software implementations and practical considerations in applying these complex methods to real cancer clinical trials. Thus, the book aims to furnish researchers in biostatistics and statistical science with a good summary of recent de