WorldWideScience

Sample records for chemoprevention

  1. Chemoprevention of Lung Cancer

    OpenAIRE

    Keith, Robert L

    2009-01-01

    Lung cancer is the leading cause of cancer death in the United States, and the majority of diagnoses are made in former smokers. While avoidance of tobacco abuse and smoking cessation clearly will have the greatest impact on lung cancer development, effective chemoprevention could prove to be more effective than treatment of established disease. Chemoprevention is the use of dietary or pharmaceutical agents to reverse or inhibit the carcinogenic process and has been successfully applied to co...

  2. Lung Cancer Chemoprevention

    OpenAIRE

    Keith, Robert L

    2012-01-01

    Lung cancer is the leading cause of cancer death in the United States, and the majority of diagnoses are made in former smokers. Although avoidance of tobacco abuse and smoking cessation clearly will have the greatest impact on lung cancer development, effective chemoprevention could prove to be more effective than treatment of established, advanced-stage disease. Chemoprevention is the use of dietary or pharmaceutical agents to reverse or block the carcinogenic process and has been successfu...

  3. Chemoprevention of Melanoma

    OpenAIRE

    Madhunapantula, SubbaRao V.; Robertson, Gavin P.

    2012-01-01

    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 h...

  4. Chemoprevention by WR-2721

    International Nuclear Information System (INIS)

    WR-2721 [S-2-(3-aminopropylamino)ethylphosphorothioic acid] is an effective chemopreventive agent. C57BL x BALB/c F1 female mice, were exposed to a single whole-body dose of 206 cGy from a 60Co 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

  5. 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...

  6. Chemoprevention of bladder cancer.

    Science.gov (United States)

    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

  7. Chemoprevention of familial adenomatous polyposis.

    Science.gov (United States)

    Lynch, Patrick M

    2016-07-01

    Familial adenomatous polyposis (FAP) has always been first and foremost a surgical disease, whose treatment with colectomy has long been known to reduce risk of premature cancer death. The notion of reducing polyp burden and potentially delaying surgical intervention has spawned a host of "chemoprevention" trials. In this paper I selectively review the findings from these studies, highlighting trial design issues and in particular some of the limitations of historical and existing trial endpoint measures. Nonsteroidal anti-inflammatory agents have been the most commonly employed chemopreventive agents. Sulindac, largely by historical accident, has been the most extensively studied, and is widely considered the standard of care when a clinical decision to intervene medically is made. Newer trials are evaluating combinations of agents in order to take advantage of differing mechanisms of action, in the hope of achieving synergy, as no single agent predictably or completely suppresses adenoma growth. Some of these studies and other single-agent interventions are discussed, though an exploration of the various mechanisms of action is beyond the scope of this paper. It is essential that future trials focus on the issue of "clinical benefit", not simply because the US Food and Drug Administration has insisted on it, but because only real evidence-based advances can improve the standard of medical care for FAP patients. Hence my focus on issues of trial design and clinically relevant endpoints. PMID:27083160

  8. Comet Assay in Cancer Chemoprevention.

    Science.gov (United States)

    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. PMID:26608293

  9. Chemopreventive Potential of Probiotics and Prebiotics

    OpenAIRE

    Rajitha Sunkata; Josh Herring; Walker, Lloyd T.; Martha Verghese

    2014-01-01

    Utilization of probiotics and prebiotics in food products and in the diet supplemental form continues to gain interest because of their health benefits. Cancer is the leading cause of death and strategies for chemoprevention are important to reduce mortality and morbidity. Probiotics are gaining attention to use as preventive agents. Efficacy of their use as chemopreventive agents was established through research. This review focused on the mechanisms of prebiotics and probiotics action again...

  10. Strategy of research for cancer-chemoprevention

    International Nuclear Information System (INIS)

    It has been reported that environmental chemicals are important factors in terms of both development and prevention of human cancer. For prevention of human cancer, detection of early cancer and clinical trials at the early stage have been focused so far. Now, next main project will be investigation for prevention of cancer development itself. Chemoprevention of carcinogenesis, which means prevention of carcinogenesis by some chemical compounds, have been investigated extensively in a variety of organs, but in only one organ. However, from results of our studies, antioxidants such as BHA, responded differently to organs, and whole body investigation, not only one organ carcinogenesis, should be performed to investigate of chemoprevention. Furthermore, the mechanisms of action of chemoprevention and on which step of carcinogenesis does the chemopreventive compound prevent, such as initiation, promotion, progression or whole carcinogenesis steps should be discussed. We have developed a medium term bioassay system and multi-organ carcinogenesis system, which can be used for investigation of cancer chemoprevention. Using these systems, we have investigated dose response inhibitory effects of BHA and α-tocopherol by the medium-term bioassay system, and catechins in the green tea inhibit small intestinal carcinogenesis in the multi-organ carcinogenesis. It is important for prevent human cancer to find other candidates for chemopreventive agents using animal study. (author)

  11. Ellagitannins in Cancer Chemoprevention and Therapy.

    Science.gov (United States)

    Ismail, Tariq; Calcabrini, Cinzia; Diaz, Anna Rita; Fimognari, Carmela; Turrini, Eleonora; Catanzaro, Elena; Akhtar, Saeed; Sestili, Piero

    2016-01-01

    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. PMID:27187472

  12. 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.

  13. [Chemoprevention of prostate cancer - a plea].

    Science.gov (United States)

    Schmitz-Dräger, B J; Bismarck, E; Schöffski, O; Fischer, C

    2012-05-01

    The high disease prevalence, the presentation in older age, a frequently slowly progressing course of disease, and high costs make the diagnosis of and therapy for prostate cancer a special challenge for urologists. Effective prevention of the disease may help to improve some of the problems mentioned above. Two randomised, controlled studies have proved that effective chemoprevention of prostate cancer is viable using 5α-reductase inhibitors (finasteride, dutasteride). Furthermore, there is increasing evidence that other compounds, e. g., selective oestrogen receptor modulators (SERMs), NSAIDs and statins might also be effective. This review investigates potential risks and benefits of chemoprevention including a consideration of health economical aspects. The authors conclude that the options of chemoprevention should be investigated in an open and unbiased way. PMID:22639024

  14. Chemoprevention of photocarcinogenesis by selected dietary botanicals.

    OpenAIRE

    Baliga, Manjeshwar S; Santosh K. Katiyar

    2006-01-01

    KEYWORDS - CLASSIFIACATION: adverse effects;Animals;Antineoplastic Agents;Antineoplastic Agents,Phytogenic;Antioxidants;chemistry;Chemoprevention;drug therapy;Dermatology;dietary modulation of cancer & cancer biomarkers;Dietary Supplements;Evaluation;Humans;methods;Neoplasms,Radiation-Induced;prevention & control;Phytotherapy;radiation effects;Research;Skin;Skin Neoplasms;therapeutic use;toxicity;Ultraviolet Rays. Epidemiological, clinical and laboratory studies have implicated solar ultra...

  15. Pancreatic Cancer Chemoprevention Translational Workshop: Meeting Report.

    Science.gov (United States)

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

    2016-09-01

    Pancreatic cancer is the fourth leading cause of cancer related deaths in the United States with a 5-year survival rate of less than 10%. The Division of Cancer Prevention of the National Cancer Institute sponsored the Pancreatic Cancer Chemoprevention Translational Workshop on September 10 to 11, 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/immunopreventative 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 National Cancer Institute working group to coordinate efforts, provide a framework, and identify opportunities for chemoprevention of pancreatic cancer. PMID:27518363

  16. Breast Cancer Chemoprevention: Old and New Approaches

    Directory of Open Access Journals (Sweden)

    Massimiliano Cazzaniga

    2012-01-01

    Full Text Available In 1976, Sporn has defined chemoprevention as “the use of pharmacologic or natural agents that inhibit the development of invasive breast cancer either by blocking the DNA damage that initiates carcinogenesis, or by arresting or reversing the progression of premalignant cells in which such damage has already occurred.” Although the precise mechanism or mechanisms that promote a breast cancer are not completely established, the success of several recent clinical trials in preventive settings in selected high-risk populations suggests that chemoprevention is a rational and an appealing strategy. Breast cancer chemoprevention has focused heavily on endocrine intervention using selective estrogen receptor modulators (SERMs and aromatase inhibitors (AIs. Achieving much success in this particular setting and new approaches as low-dose administration are actually under investigations in several topics. Unfortunately, these drugs are active in prevention of endocrine responsive lesions only and have no effect in reducing the risk of estrogen-negative breast cancer. Thus, recently new pathways, biomarkers, and agents likely are to be effective in this subgroup of cancers and were put under investigation. Moreover, the identification of new potential molecular targets and the development of agents aimed at these targets within cancer have already had a significant impact on advanced cancer therapy and provide a wealth of opportunities for chemoprevention. This paper will highlight current clinical research in both ER-positive and ER-negative breast cancer chemoprevention, explaining the biologic effect of the various agents on carcinogenesis and precancerous lesions, and finally presenting an excursus on the state-of-the-art about new molecular targets under investigations in breast cancer settings.

  17. 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

  18. Dietary chalcones with chemopreventive and chemotherapeutic potential.

    Science.gov (United States)

    Orlikova, Barbora; Tasdemir, Deniz; Golais, Frantisek; Dicato, Mario; Diederich, Marc

    2011-05-01

    Chalcones are absorbed in the daily diet and appear to be promising cancer chemopreventive agents. Chalcones represent an important group of the polyphenolic family, which includes a large number of naturally occurring molecules. This family possesses an interesting spectrum of biological activities, including antioxidative, antibacterial, anti-inflammatory, anticancer, cytotoxic, and immunosuppressive potential. Compounds of this family have been shown to interfere with each step of carcinogenesis, including initiation, promotion and progression. Moreover, numerous compounds from the family of dietary chalcones appear to show activity against cancer cells, suggesting that these molecules or their derivatives may be considered as potential anticancer drugs. This review will focus primarily on prominent members of the chalcone family with an 1,3-diphenyl-2-propenon core structure. Specifically, the inhibitory effects of these compounds on the different steps of carcinogenesis that reveal interesting chemopreventive and chemotherapeutic potential will be discussed. PMID:21484163

  19. Breast Cancer Chemoprevention: Old and New Approaches

    OpenAIRE

    Massimiliano Cazzaniga; Bernardo Bonanni

    2012-01-01

    In 1976, Sporn has defined chemoprevention as “the use of pharmacologic or natural agents that inhibit the development of invasive breast cancer either by blocking the DNA damage that initiates carcinogenesis, or by arresting or reversing the progression of premalignant cells in which such damage has already occurred.” Although the precise mechanism or mechanisms that promote a breast cancer are not completely established, the success of several recent clinical trials in preventive settings i...

  20. Preclinical Assays for Identifying Cancer Chemopreventive Phytochemicals

    OpenAIRE

    Oyama, Takeru; Yasui, Yumiko; Sugie, Shigeyuki; Tanaka, Takuji

    2009-01-01

    Dietary factors influence carcinogenesis in a variety of tissues. The consumption of fruits and vegetables is associated with a decreased risk of several types of epithelial malignancies. In addition, there are interrelationships between diet, environmental factors, and genetics that can affect cancer risk. Potential chemopreventive agents against cancer development can be found among nutritive and/or nonnutritive compounds in inedible and edible plants. To identify potential cancer chemoprev...

  1. Ellagitannins in Cancer Chemoprevention and Therapy

    OpenAIRE

    Tariq Ismail; Cinzia Calcabrini; Anna Rita Diaz; Carmela Fimognari; Eleonora Turrini; Elena Catanzaro; Saeed Akhtar; Piero Sestili

    2016-01-01

    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 i...

  2. A review of cancer chemopreventive agents.

    Science.gov (United States)

    Levi, M S; Borne, R F; Williamson, J S

    2001-09-01

    In the late 20(th) century, the treatment of cancer began to include its prevention. Today, compounds exist that will lower the risk of developing certain types of cancer. This has been demonstrated in studies where chemically induced tumor growth has been slowed or reversed. Anti-inflammatory compounds having chemopreventive activity are piroxicam, sulindac, aspirin, celecoxib and curcumin. The selective estrogen receptor modulators, tamoxifen and raloxifene, are beneficial in the prevention of estrogen dependent tumors. Retinoids, vitamin A derivatives, such as targretin and fenretinide are useful in the prevention of tumors. Compounds containing sulfur, such as sulforaphane and oltipraz, are even useful as radioprotective agents. The steroid dehydroepiandosterone can inhibit experimental carcinogenesis. All of these chemical classes provide a start for the medicinal chemist to design more effective chemopreventive agents. The biomarkers used to determine the chemopreventive activity of new compounds are quite often activities of enzymes. The identification of those individuals at high risk is still in its infancy and presents a troubling dilemma. PMID:11562271

  3. 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.

  4. Beneficial and adverse effects of chemopreventive agents

    International Nuclear Information System (INIS)

    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

  5. Chemoprevention of esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Esophageal squamous cell carcinoma (SCC) is responsible for approximately one-sixth of all cancer-related mortality worldwide. This malignancy has a multifactorial etiology involving several environmental, dietary and genetic factors. Since esophageal cancer has often metastasized at the time of diagnosis, current treatment modalities offer poor survival and cure rates. Chemoprevention offers a viable alternative that could well be effective against the disease. Clinical investigations have shown that primary chemoprevention of this disease is feasible if potent inhibitory agents are identified. The Fischer 344 (F-344) rat model of esophageal SCC has been used extensively to investigate the biology of the disease, and to identify chemopreventive agents that could be useful in human trials. Multiple compounds that inhibit tumor initiation by esophageal carcinogens have been identified using this model. These include several isothiocyanates, diallyl sulfide and polyphenolic compounds. These compounds influence the metabolic activation of esophageal carcinogens resulting in reduced genetic (DNA) damage. Recently, a few agents have been shown to inhibit the progression of preneoplastic lesions in the rat esophagus into tumors. These agents include inhibitors of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) and c-Jun [a component of activator protein-1 (AP-1)]. Using a food-based approach to cancer prevention, we have shown that freeze-dried berry preparations inhibit both the initiation and promotion/progression stages of esophageal SCC in F-344 rats. These observations have led to a clinical trial in China to evaluate the ability of freeze-dried strawberries to influence the progression of esophageal dysplasia to SCC

  6. Overview of mechanisms of cancer chemopreventive agents

    International Nuclear Information System (INIS)

    Epidemiological data provide evidence that it is possible to prevent cancer and other chronic diseases, some of which share common pathogenetic mechanisms, such as DNA damage, oxidative stress, and chronic inflammation. An obvious approach is avoidance of exposure to recognized risk factors. As complementary strategies, it is possible to render the organism more resistant to mutagens/carcinogens and/or to inhibit progression of the disease by administering chemopreventive agents. In a primary prevention setting, addressed to apparently healthy individuals, it is possible to inhibit mutation and cancer initiation by triggering protective mechanisms either in the extracellular environment or inside cells, e.g., by modifying transmembrane transport, modulating metabolism, blocking reactive species, inhibiting cell replication, maintaining DNA structure, modulating DNA metabolism and repair, and controlling gene expression. Tumor promotion can be counteracted by inhibiting genotoxic effects, favoring antioxidant and anti-inflammatory activity, inhibiting proteases and cell proliferation, inducing cell differentiation, modulating apoptosis and signal transduction pathways, and protecting intercellular communications. In a secondary prevention setting, when a premalignant lesion has been detected, it is possible to inhibit tumor progression via the same mechanisms, and in addition by affecting the hormonal status and the immune system in various ways, and by inhibiting tumor angiogenesis. Although tertiary prevention, addressed to cancer patients after therapy, is outside the classical definition of chemoprevention, it exploits similar mechanisms. It is also possible to affect cell-adhesion molecules, to activate antimetastasis genes, and to inhibit proteases involved in basement membrane degradation

  7. Phyto-oestrogens and breast cancer chemoprevention

    International Nuclear Information System (INIS)

    Phytoestrogens are polyphenol compounds of plant origin that exhibit a structural similarity to the mammalian steroid hormone 17β-oestradiol. In Asian nations the staple consumption of phyto-oestrogen-rich foodstuffs correlates with a reduced incidence of breast cancer. Human dietary intervention trials have noted a direct relationship between phyto-oestrogen ingestion and a favourable hormonal profile associated with decreased breast cancer risk. However, these studies failed to ascertain the precise effect of dietary phyto-oestrogens on the proliferation of mammary tissue. Epidemiological and rodent studies crucially suggest that breast cancer chemoprevention by dietary phyto-oestrogen compounds is dependent on ingestion before puberty, when the mammary gland is relatively immature. Phyto-oestrogen supplements are commercially marketed for use by postmenopausal women as natural and safe alternatives to hormone replacement therapy. Of current concern is the effect of phyto-oestrogen compounds on the growth of pre-existing breast tumours. Data are contradictory, with cell culture studies reporting both the oestrogenic stimulation of oestrogen receptor-positive breast cancer cell lines and the antagonism of tamoxifen activity at physiological phyto-oestrogen concentrations. Conversely, phyto-oestrogen ingestion by rodents is associated with the development of less aggressive breast tumours with reduced metastatic potential. Despite the present ambiguity, current data do suggest a potential benefit from use of phyto-oestrogens in breast cancer chemoprevention and therapy. These aspects are discussed

  8. Cancer Chemopreventive Ability of Conjugated Linolenic Acids

    Directory of Open Access Journals (Sweden)

    Kazuo Miyashita

    2011-11-01

    Full Text Available Conjugated fatty acids (CFA have received increased interest because of their beneficial effects on human health, including preventing cancer development. Conjugated linoleic acids (CLA are such CFA, and have been reviewed extensively for their multiple biological activities. In contrast to other types of CFAs including CLA that are found at low concentrations (less than 1% in natural products, conjugated linolenic acids (CLN are the only CFAs that occur in higher quantities in natural products. Some plant seeds contain a considerably high concentration of CLN (30 to 70 wt% lipid. Our research group has screened CLN from different plant seed oils to determine their cancer chemopreventive ability. This review describes the physiological functions of CLN isomers that occur in certain plant seeds. CLN are able to induce apoptosis through decrease of Bcl-2 protein in certain human cancer cell lines, increase expression of peroxisome proliferator-activated receptor (PPAR-γ, and up-regulate gene expression of p53. Findings in our preclinical animal studies have indicated that feeding with CLN resulted in inhibition of colorectal tumorigenesis through modulation of apoptosis and expression of PPARγ and p53. In this review, we summarize chemopreventive efficacy of CLN against cancer development, especially colorectal cancer.

  9. Chemoprevention of prostate cancer by isoflavonoids.

    Science.gov (United States)

    Aufderklamm, Stefan; Miller, Florian; Galasso, Anastasia; Stenzl, Arnulf; Gakis, Georgios

    2014-01-01

    In Europe, prostate cancer (PC) is the most common malignancy in males. There are three known risk factors strongly coherent to the development of PC: heredity, ethnical origin, and age. Migration studies have shown that environmental factors may influence the development of PC. In this context, specific nutritional components may exert an influence on the tumorigenesis of PC. Primary prevention of PC is still an important issue due to its high prevalence, treatment-associated morbidities, and long-term complications. Phytoestrogenes as flavonoids seem to play an essential role in the chemoprevention of PC which is possibly due to their hormonal function and antioxidative capability. Flavonoids and their subgroups are naturally existent in traditional asian and vegetarian nutrients as coverings of plants, fruits, and vegetables. Two of the most frequently investigated flavonoids are genistein and quercetin. These nutritional components may have therapeutic potential and may impact the development of PC. Even though these flavonoids show promising results in the chemoprevention of PC, the literature is almost experimental, epidemiological, and retrospective with a missing long-term follow-up. Therefore, randomized clinical trials are urgently needed to evaluate in depth its oncologic effects in PC. PMID:24531783

  10. Beer constituents as potential cancer chemopreventive agents.

    Science.gov (United States)

    Gerhäuser, Clarissa

    2005-09-01

    Beer is a complex alcoholic beverage made from barley (malt), hop, water and yeast. Phenolic constituents of beer are derived from malt (70-80%) and hop (20-30%). Structural classes include simple phenols, benzoic- and cinnamic acid derivatives, coumarins, catechins, di-, tri- and oligomeric proanthocyanidins, (prenylated) chalcones and flavonoids as well as alpha- and iso-alpha-acids derived from hop. Compounds belonging to different structural classes have distinct profiles of biological activity in in vitro test systems, and in combination might lead to enhanced effects. Scientific evidence has accumulated over the past 10 years pointing to the cancer preventive potential of selected hop-derived beer constituents, i.e., prenylflavonoids including xanthohumol and isoxanthohumol, and hop bitter acids. Chemopreventive activities observed with these compounds relevant to inhibition of carcinogenesis at the initiation, promotion and progression phases, as well as results from in vivo studies on metabolism, bioavailability and efficacy are summarised in this review. PMID:15953717

  11. Chemopreventive Herbal Anti-Oxidants: Current Status and Future Perspectives

    OpenAIRE

    Patel, Rachana; Garg, Rachana; Erande, Suvarna; B. Maru, Girish

    2007-01-01

    Cancer chemoprevention is fast becoming a lucrative approach for controlling cancer. Carcinogenesis being a complex multi-step, multi-factorial process, a number of chemopreventive interventions can be employed. These strategies are generally directed against two broad events of carcinogenesis viz., initiation and promotion/progression. Anti-initiation interventions principally involve inhibition of carcinogen activation, scavenging of free radicals and reactive carcinogen metabolites along w...

  12. Molecular Targeted Therapies Using Botanicals for Prostate Cancer Chemoprevention

    OpenAIRE

    Kumar, Nagi; Chornokur, Ganna

    2012-01-01

    In spite of the large number of botanicals demonstrating promise as potential cancer chemopreventive agents, most have failed to prove effectiveness in clinical trials. Critical requirements for moving botanical agents to recommendation for clinical use include adopting a systematic, molecular-target based approach and utilizing the same ethical and rigorous methods that are used to evaluate other pharmacological agents. Preliminary data on a mechanistic rationale for chemoprevention activity...

  13. The Use of Animal Models for Cancer Chemoprevention Drug Development

    OpenAIRE

    Steele, Vernon E.; Lubet, Ronald A.

    2010-01-01

    Animal models currently are used to assess the efficacy of potential chemopreventive agents, including synthetic chemicals, chemical agents obtained from natural products and natural product mixtures. The observations made in these models as well as other data are then used to prioritize agents to determine which are qualified to progress to clinical chemoprevention trials. Organ specific animal models are employed to determine which agents or classes of agents are likely to be the most effec...

  14. Chemoprevention--history and general principles.

    Science.gov (United States)

    Wu, Xiangwei; Patterson, Sherri; Hawk, Ernest

    2011-08-01

    Our current understanding of tumourigenesis suggests that cancer develops as a series of cumulative genetic and epigenetic derangements across time culminating in a clone of cells differing from its population of origin in terms of cellular identity, growth control, and its contextual relationship to its environment. Our increasing knowledge of the timing, sequence, frequency, and specific implications of these changes provides unique opportunities for earlier identification of aberrations and preventive interventions. Here we discuss the fundamentals of cancer prevention including the targets, cohorts, agents, endpoints, mechanistic biomarkers, designs, and strategies employed in preventive drug development. There have been many notable successes in this field such as the identification and development of tamoxifen and raloxifene for breast cancer risk reduction, instillational BCG and valrubicin for treatment of preinvasive bladder cancer, and a variety of topical and systemic agents that effectively treat preinvasive neoplastic lesions of the skin. A variety of null or negative developmental endeavours have occurred as well, including trials of beta-carotene for lung cancer prevention, nutritional modifications for colorectal adenoma prevention, and most recently, selenium and alpha-tocopherol for prostate cancer prevention. A third category of prevention trials can be summarized as investigationally successful, but not achieving regulatory success. The development of finasteride and dutasteride for prostate cancer prevention, and celecoxib for colorectal neoplasia prevention fall into this category. In less than four decades, cancer chemoprevention has transformed from a concept to an achievable reality. PMID:22122762

  15. Advanced drug delivery systems of curcumin for cancer chemoprevention.

    Science.gov (United States)

    Bansal, Shyam S; Goel, Mehak; Aqil, Farrukh; Vadhanam, Manicka V; Gupta, Ramesh C

    2011-08-01

    Since ancient times, chemopreventive agents have been used to treat/prevent several diseases including cancer. They are found to elicit a spectrum of potent responses including anti-inflammatory, antioxidant, antiproliferative, anticarcinogenic, and antiangiogenic activity in various cell cultures and some animal studies. Research over the past 4 decades has shown that chemopreventives affect a number of proteins involved in various molecular pathways that regulate inflammatory and carcinogenic responses in a cell. Various enzymes, transcription factors, receptors, and adhesion proteins are also affected by chemopreventives. Although, these natural compounds have shown significant efficacy in cell culture studies, they elicited limited efficacy in various clinical studies. Their introduction into the clinical setting is hindered largely by their poor solubility, rapid metabolism, or a combination of both, ultimately resulting in poor bioavailability upon oral administration. Therefore, to circumvent these limitations and to ease their transition to clinics, alternate strategies should be explored. Drug delivery systems such as nanoparticles, liposomes, microemulsions, and polymeric implantable devices are emerging as one of the viable alternatives that have been shown to deliver therapeutic concentrations of various potent chemopreventives such as curcumin, ellagic acid, green tea polyphenols, and resveratrol into the systemic circulation. In this review article, we have attempted to provide a comprehensive outlook for these delivery approaches, using curcumin as a model agent, and discussed future strategies to enable the introduction of these highly potent chemopreventives into a physician's armamentarium. PMID:21546540

  16. 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

  17. 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.

  18. Prostate cancer chemoprevention: Current status and future prospects

    International Nuclear Information System (INIS)

    Chemoprevention is a strategy that aims to reduce the incidence and burden of cancer through the development of agents to prevent, reverse or delay the carcinogenic process. Prostate cancer is a suitable target for prevention because it has a high incidence and prevalence, as well as a long latency and disease-related mortality, and furthermore it is a disease in which lifestyle and environmental factors may play critical roles. The development of chemoprevention strategies against prostate cancer will have a huge impact, both medically and economically. Large-scale clinical trials suggest that some agents such as selenium, lycopene, soy, green tea, vitamins D and E, anti-inflammatory and inhibitors of 5α-reductase are effective in preventing prostate cancer. Although each agent has the potential to affect the natural history of the disease, it is important to develop strategies to strategically proceed for the design and selection of test agents in order to demonstrate clinical benefit with the minimum of adverse effects. Appropriate selection of agent(s), disease stage, trial design and endpoints is critical in selecting the most promising regimens to accomplish these goals. This review highlights the present status of prostate cancer chemoprevention and discusses future prospects for chemopreventive strategies that are safe and clinically beneficial

  19. Is There a Future for Chemoprevention of Prostate Cancer?

    Science.gov (United States)

    Bosland, Maarten C

    2016-08-01

    The outcome of the Selenium and Vitamin E Cancer Prevention Trial, demonstrating harm and no preventive activity of selenomethionine and α-tocopherol for prostate cancer, and the lack of approval by the FDA for the use of 5α-reductase inhibitors to prevent prostate cancer have cast doubt about the future of chemoprevention of prostate cancer. This article attempts to critically assess whether the notion that chemoprevention of prostate cancer has no future is warranted. Risk of prostate cancer is modifiable and chemoprevention of prostate cancer, particularly fatal/lethal cancer, is both needed and possible. However, the approach to prostate cancer-chemopreventive agent development has not followed a rational and systematic process. To make progress, the following steps are necessary: (i) identification of intermediate biomarkers predictive of fatal/lethal disease; (ii) development of a rational approach to identification of candidate agents, including high-throughput screening and generation of information on mechanism and biology of candidate agents and potential molecular targets; and (iii) systematic evaluation of the predictive value of preclinical models, phase II trials, and intermediate biomarkers for the outcome of phase III trials. New phase III trials should be based on adequate preclinical and phase II studies. Cancer Prev Res; 9(8); 642-7. ©2016 AACR. PMID:27099271

  20. Chemoprevention of prostate cancer with nutrients and supplements.

    Science.gov (United States)

    Van Poppel, Hendrik; Tombal, Bertrand

    2011-01-01

    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. PMID:21629831

  1. Risk adapted chemoprevention for prostate cancer: an option?

    Science.gov (United States)

    Schmitz-Dräger, Bernd J; Schöffski, Oliver; Marberger, Michael; Sahin, Sevim; Schmid, Hans-Peter

    2014-01-01

    A high disease prevalence, the presentation in older age, a frequently slowly progressing course of disease, and high costs make diagnosis and therapy of prostate cancer a special challenge for urologists. Effective prevention of the disease may help to resolve some of the problems mentioned above. Two randomised, controlled studies prove that effective chemoprevention of prostate cancer is possible using 5-α reductase inhibitors (finasteride, dutasteride) (LoE 1) both in individuals at low and those at high risk developing prostate cancer. Furthermore, there is evidence that other compounds, e.g. selective estrogen receptor modulators (SERMs), non-steroidal anti-inflammatory drugs (NSAIDs) and statins might also be effective. This review investigates potential risks and benefits of chemoprevention including a consideration of health economic aspects. The authors conclude that chemoprevention in a high risk cohort using 5-α reductase inhibitors is a viable option and may even be cost effective. In consequence, the options of chemoprevention in prostate cancer should be further explored in an open and unbiased way. PMID:24531781

  2. Keap1 eye on the target: chemoprevention of liver cancer

    Institute of Scientific and Technical Information of China (English)

    Melinda Sue YATES; Thomas Wells KENSLER

    2007-01-01

    Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide,causing nearly 600000 deaths each year. Increased risk of HCC due to chronic infection with hepatitis B virus (HBV) and exposure to dietary aflatoxins is respon-sible for many of these deaths. Prevention strategies targeting HBV infection and aflatoxin exposure could dramatically impact the rates of HCC. Universal HBV vaccination programs have begun in some high-risk areas. Strategies to reduce aflatoxin contamination in food stores have also been implemented. However,complete elimination of aflatoxin contamination might not be possible. For this reason, chemoprevention strategies which alter aflatoxin disposition are a practi-cal strategy to reduce the incidence of HCC in populations with high dietary aflatoxin exposure. The mechanisms of aflatoxin-induced hepatocarcinogenesis are well known. This knowledge provides the basis for evaluation of both expo-sures to aflatoxin, as well as modulation of aflatoxin disposition by chemopreventive agents. Products of aflatoxin DNA damage and toxicity as well as other metabo-lites can be used as biomarkers to evaluate modulation of aflatoxin disposition.Modulation of aflatoxin disposition can be achieved through induction of conju-gating and cytoprotective enzymes. Many of these enzymes are regulated through Kelch ECH-associating protein 1 (Keap 1)-NF-E2-related factor 2(Nrf2)-antioxi-dant response element (ARE) signaling, making this pathway an important mo-lecular target for chemoprevention. Rodent studies have identified several classes of chemopreventive agents which induce cytoprotective genes. These inducers include phenolic antioxidants, dithiolethiones, isothiocyanates, and triterpenoids.Furthermore, clinical interventions have shown that inducers of Keap 1-Nrf2-ARE signaling increase cytoprotective enzyme expression, resulting in modula-tion of aflatoxin disposition. Much work remains to be done in order to take promising chemopreventive

  3. The role of natural dietary compounds in colorectal cancer chemoprevention

    Directory of Open Access Journals (Sweden)

    Anna Olejnik

    2010-04-01

    Full Text Available 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. [i]In vitro[/i] 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.

  4. 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

  5. The Mechanism in Gastric Cancer Chemoprevention by Allicin.

    Science.gov (United States)

    Luo, Runlan; Fang, Dengyang; Hang, Hongdong; Tang, Zeyao

    2016-01-01

    Gastric cancer remains high prevalence and fatality rates in China even though its morbidity has been decreased drastically. Allicin, which is from an assistance food-garlic (Allium Sativum L), was found to be effective in gastric cancer treatment. It is a defensive substance with a board biological properties: inhibition of bacteria, fungus, virus, controlled hypertension, diabetes, and chemoprevention of several cancers, etc. Experiments have shown that allicin can be chemopreventive to gastric cancer by inhibiting the growth of cancer cells, arresting cell cycle at G2/M phase, endoplasmic reticulum (ER) stress, and mitochondria-mediated apoptosis, which includes the caspase-dependent/-independent pathways and death receptor pathway. Those mechanisms probably involve in modulating enzymatic activity, restraining DNA formation, scavenging free radicals, and affecting cell proliferation and even tumor growth. Therefore, this review is focus on the mechanism of allicin in gastric cancer. PMID:26555611

  6. 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.

  7. Evidence supporting the conceptual framework of cancer chemoprevention in canines.

    Science.gov (United States)

    Kondratyuk, Tamara P; Adrian, Julie Ann Luiz; Wright, Brian; Park, Eun-Jung; van Breemen, Richard B; Morris, Kenneth R; Pezzuto, John M

    2016-01-01

    As with human beings, dogs suffer from the consequences of cancer. We investigated the potential of a formulation comprised of resveratrol, ellagic acid, genistein, curcumin and quercetin to modulate biomarkers indicative of disease prevention. Dog biscuits were evaluated for palatability and ability to deliver the chemopreventive agents. The extent of endogenous DNA damage in peripheral blood lymphocytes from dogs given the dietary supplement or placebo showed no change. However, H2O2-inducible DNA damage was significantly decreased after consumption of the supplement. The expression of 11 of 84 genes related to oxidative stress was altered. Hematological parameters remained in the reference range. The concept of chemoprevention for the explicit benefit of the canine is compelling since dogs are an important part of our culture. Our results establish a proof-of-principle and provide a framework for improving the health and well-being of "man's best friend". PMID:27216246

  8. 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.

  9. Chemoprevention of lung squamous cell carcinoma by ginseng.

    Science.gov (United States)

    Pan, Jing; Zhang, Qi; Li, Kezhen; Liu, Qian; Wang, Yian; You, Ming

    2013-06-01

    Ginseng has been used as a medicinal herb to maintain physical vitality for thousands of years, and it has also been shown to be a nonorgan-specific cancer preventive agent by several epidemiologic studies. However, the chemopreventive effects of Korea white ginseng (KWG) in lung squamous cell carcinoma (SCC) have not been tested. In this study, we investigated the chemopreventive activity of KWG in a mouse lung SCC model. N-nitroso-trischloroethylurea (NTCU) was used to induce lung tumors in female Swiss mice, and KWG was given orally. KWG significantly reduced the percentage of lung SCCs from 26.5% in the control group to 9.1% in the KWG group and in the meantime, increased the percentage of normal bronchial and hyperplasia. KWG was also found to greatly reduce squamous cell lung tumor area from an average of 9.4% in control group to 1.5% in the KWG group. Treatment with KWG decreased Ki-67 staining, suggesting that the lung tumor inhibitory effects of KWG were partly through inhibition of proliferation. High-performance liquid chromatography/mass spectrometry identified 10 ginsenosides from KWG extracts, Rb1 and Rd being the most abundant as detected in mouse blood and lung tissue. The tumor inhibitory effects of KWG are mediated by inhibition of activator protein (AP-1), as showed by in vitro study conducted on AP-1/NF-κB-dependent mouse non-small cell lung carcinoma cell lines. Western blotting of lung tissues also indicated that NTCU upregulated AP-1 through phosphorylation of c-jun-NH2-kinase, which was downregulated by KWG in concurrence with its chemoprevention function. These results suggest that KWG could be a potential chemopreventive agent for lung SCC. PMID:23550152

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

    OpenAIRE

    Prasan R Bhandari

    2015-01-01

    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 readil...

  11. Chemopreventive effect of apple and berry fruits against colon cancer

    OpenAIRE

    Jaganathan, Saravana Kumar; Vellayappan, Muthu Vignesh; Narasimhan, Gayathri; Supriyanto, Eko; Octorina Dewi, Dyah Ekashanti; Narayanan, Aqilah Leela T; Balaji, Arunpandian; Subramanian, Aruna Priyadarshini; Yusof, Mustafa

    2014-01-01

    Colon cancer arises due to the conversion of precancerous polyps (benign) found in the inner lining of the colon. Prevention is better than cure, and this is very true with respect to colon cancer. Various epidemiologic studies have linked colorectal cancer with food intake. Apple and berry juices are widely consumed among various ethnicities because of their nutritious values. In this review article, chemopreventive effects of these fruit juices against colon cancer are discussed. Studies de...

  12. Discovery and development of sulforaphane as a cancer chemopreventive phytochemical

    Institute of Scientific and Technical Information of China (English)

    Yuesheng ZHANG; Li TANG

    2007-01-01

    Sulforaphane (SF) is a phytochemical that displays both anticarcinogenic and anticancer activity. SF modulates many cancer-related events, including suscep-tibility to carcinogens, cell death, cell cycle, angiogenesis, invasion and metastasis.We review its discovery and development as a cancer chemopreventive agent with the intention of encouraging further research on this important compound and facilitating the identification and development of new phytochemicals for cancer prevention.

  13. Colon cancer chemoprevention with ginseng and other botanicals.

    OpenAIRE

    Wargovich, M J

    2001-01-01

    Colorectal cancer is becoming increasingly common in Asian countries and still remains the second leading cause of cancer deaths in the United States. Efforts to prevent colon cancer have targeted early detection through screening and chemoprevention. For the last ten years our laboratory has utilized an in vivo screening assay for the testing of potential cancer preventives for colon cancer. We have conducted investigations on over 150 compounds including many with botanical or herbal origin...

  14. 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.

  15. 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.

  16. The strategies to control prostate cancer by chemoprevention approaches

    International Nuclear Information System (INIS)

    Prostate cancer (PCA) is the most commonly diagnosed cancer in men in the United States with growing worldwide incidence. Despite intensive investment in improving early detection, PCA often escapes timely detection and mortality remains high; this malignancy being the second highest cancer-associated mortality in American men. Collectively, health care costs of PCA results in an immense financial burden that is only expected to grow. Additionally, even in cases of successful treatment, PCA is associated with long-term and pervasive effects on patients. A proactive alternative to treat PCA is to prevent its occurrence and progression prior to symptomatic malignancy. This may serve to address the issue of burgeoning healthcare costs and increasing number of sufferers. One potential regimen in service of this alternative is PCA chemoprevention. Here, chemical compounds with cancer preventive efficacy are identified on the basis of their potential in a host of categories: their historical medicinal use, correlation with reduced risk in population studies, non-toxicity, their unique chemical properties, or their role in biological systems. PCA chemopreventive agents are drawn from multiple broad classes of chemicals, themselves further subdivided based on source or potential effect, with most derived from natural products. Many such compounds have shown efficacy, varying from inhibiting deregulated PCA cell signaling, proliferation, epithelial to mesenchymal transition (EMT), invasion, metastasis, tumor growth and angiogenesis and inducing apoptosis. Overall, these chemopreventive agents show great promise in PCA pre-clinical models, though additional work remains to be done in effectively translating these findings into clinical use

  17. Estrogen intracrinology: therapy and chemoprevention of breast cancer

    Directory of Open Access Journals (Sweden)

    Barbara Licznerska

    2010-05-01

    Full Text Available Breast cancer affects approximately 1 in 10 women and is the leading cause of death in females between the ages of 40 and 50 years in the Western world. The World Health Organization (WHO classified estrogens as carcinogenic in humans and one of the most important risk factors of breast cancer. One of the main arguments has been that estrogens can not only promote cancers but may also initiate mutations caused by certain estrogen metabolites. Therapeutics and chemopreventive agents (e.g. tamoxifen currently in use for breast cancer generally act through an estrogen receptor (ER mechanism and are thus inappropriate for estrogen-independent disease. In the last decade, numerous studies have searched for new therapeutic and preventive agents acting independently of ER status, hence suitable for cases of estrogen-independent breast cancer. In postmenopausal women, when gonads stop producing estrogens, active hormones are produced locally. These locally produced bioactive estrogens exert their actions in the cells of tissues that have not been considered classical hormone-producing sites (i.e. breast cancer tissue and where synthesis occurs without release into the circulation. This mechanism has been termed “intracrinology”, a phenomenon different from the classical concept of endocrinology. Interference in the local production of estrogens seems to be a good alternative to chemotherapy and chemoprevention of breast carcinoma. In this article, crucial enzymes in estrogen’s biosynthesis in the breast and their potential use in therapy and chemoprevention are discussed.

  18. Chain elongation analog of resveratrol as potent cancer chemoprevention agent.

    Science.gov (United States)

    Kang, Yan-Fei; Qiao, Hai-Xia; Xin, Long-Zuo; Ge, Li-Ping

    2016-09-01

    Resveratrol is identified as a natural cancer chemoprevention agent. There has been a lot of interest in designing and developing resveratrol analogs with cancer chemoprevention activity superior to that of parent molecule and exploring their action mechanism in the past several decades. In this study, we have synthesized resveratrol analogs of compounds A-C via conjugated chain elongation based on isoprene unit retention strategy. Remarkably, cytotoxic activity analysis results indicated that compound B possesses the best proliferation inhibition activity for NCI-H460 cells in all the test compounds. Intriguingly, compound B displayed a higher cytotoxicity against human non-small cell lung cancer cells (NCI-H460) compared to normal human embryonic lung fibroblasts (MRC-5). Afterward, flow cytometry analysis showed that compound B would induce cell apoptosis. We further researched the action mechanism. When NCI-H460 cells were incubated by compound B for 6 or 9 h, respectively, the intracellular reactive oxygen species (ROS) level was enhanced obviously. With elevation of intracellular ROS level, flow cytometry measurement verified mitochondrial transmembrane potential collapse, which was accompanied by the up-regulation of Bax and down-regulation of Bcl-2. More interestingly, compound B increased the expression of caspase-9 and caspase-3, which induced cell apoptosis. Moreover, compound B arrested cell cycle in G0/G1 phase. These are all to provide useful information for designing resveratrol-based chemoprevention agent and understanding the action mechanism. PMID:27160168

  19. The strategies to control prostate cancer by chemoprevention approaches

    Energy Technology Data Exchange (ETDEWEB)

    Ting, Harold [Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO (United States); Deep, Gagan; Agarwal, Chapla [Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO (United States); University of Colorado Cancer Center, University of Colorado, Aurora, CO (United States); Agarwal, Rajesh, E-mail: Rajesh.Agarwal@UCDenver.edu [Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO (United States); University of Colorado Cancer Center, University of Colorado, Aurora, CO (United States)

    2014-02-15

    Prostate cancer (PCA) is the most commonly diagnosed cancer in men in the United States with growing worldwide incidence. Despite intensive investment in improving early detection, PCA often escapes timely detection and mortality remains high; this malignancy being the second highest cancer-associated mortality in American men. Collectively, health care costs of PCA results in an immense financial burden that is only expected to grow. Additionally, even in cases of successful treatment, PCA is associated with long-term and pervasive effects on patients. A proactive alternative to treat PCA is to prevent its occurrence and progression prior to symptomatic malignancy. This may serve to address the issue of burgeoning healthcare costs and increasing number of sufferers. One potential regimen in service of this alternative is PCA chemoprevention. Here, chemical compounds with cancer preventive efficacy are identified on the basis of their potential in a host of categories: their historical medicinal use, correlation with reduced risk in population studies, non-toxicity, their unique chemical properties, or their role in biological systems. PCA chemopreventive agents are drawn from multiple broad classes of chemicals, themselves further subdivided based on source or potential effect, with most derived from natural products. Many such compounds have shown efficacy, varying from inhibiting deregulated PCA cell signaling, proliferation, epithelial to mesenchymal transition (EMT), invasion, metastasis, tumor growth and angiogenesis and inducing apoptosis. Overall, these chemopreventive agents show great promise in PCA pre-clinical models, though additional work remains to be done in effectively translating these findings into clinical use.

  20. 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.

  1. 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; Raskov, Hans

    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....

  2. 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.

  3. 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

  4. Genistein chemoprevention of prostate cancer in TRAMP mice

    Directory of Open Access Journals (Sweden)

    Eltoum Isam-Eldin

    2007-01-01

    Full Text Available Abstract Epidemiological studies suggest an inverse association between soy intake and prostate cancer risk. Genistein, the predominant phytoestrogen in soy food, has been proposed as a potential chemopreventive agent due to its anti-estrogen and tyrosine kinase inhibitory effects. To determine the most effective period for genistein chemoprevention, the Transgenic adenocarcinoma mouse prostate (TRAMP model was used. The treatments were 250 mg genistein/kg AIN-76A diet 1 prepubertally only, 2 in adulthood only or 3 through out life. Controls received AIN-76A diet. By 28 weeks of age, 100% TRAMP mice fed control diet developed prostatic intraepithelial neoplasia (PIN or adenocarcinomas with 6%, 16%, 44% and 34% developing high grade PIN, well differentiated, moderately differentiated and poorly differentiated prostatic adenocarcinomas, respectively. Prepubertal only (1–35 days postpartum and adult only genistein treatments (12 – 28 weeks resulted in 6% and 29% decreases in poorly-differentiated cancerous lesions compared with controls, respectively. The most significant effect was seen in the TRAMP mice exposed to genistein throughout life (1–28 weeks with a 50% decrease in poorly-differentiated cancerous lesions. In a separate experiment in castrated TRAMP mice, dietary genistein suppressed the development of advanced prostate cancer by 35% compared with controls. Of the tumors that developed in castrated TRAMP mice, 100% were poorly-differentiated in contrast to the 37% of noncastrated TRAMP mice that developed poorly-differentiated tumors. ICI 182,780 (ICI, genistein and estrogen down-regulated androgen receptor (AR, estrogen receptor alpha (ER-α and progesterone receptor (PR in the prostates of C57BL/6 mice, and act independently of ER. Our data obtained in intact and castrated transgenic mice suggest that genistein may be a promising chemopreventive agent against androgen-dependent and independent prostate cancers.

  5. Implications for chemoprevention of prostate cancer with intake of cruciferous vegetables

    Institute of Scientific and Technical Information of China (English)

    Jeanny B Aragon-Ching

    2011-01-01

    @@ Efforts on chemoprevention have been an attractive target of investigation for prostate cancer.Since prostate cancer is the most common non-cutaneous malignancy among American men, efforts for chemopreventative strategies make sense.However, such undertaking has been wrought with problems and wide-scale efforts to launch drug chemoprevention have been dampened by mixed results.

  6. Targeting multiple signal pathways by chemopreventive agents for cancer prevention and therapy

    Institute of Scientific and Technical Information of China (English)

    Fazlul H SARKAR; Yi-wei LI

    2007-01-01

    In recent years, growing interest has been focused on the field of cancer prevention.Cancer prevention by chemopreventive agents offers significant promise for re-ducing the incidence and mortality of cancer. Chemopreventive agents may exert their effects either by blocking or metabolizing carcinogens or by inhibiting tumor cell growth. Another important benefit of chemopreventive agents is their non-toxic nature. Therefore, chemopreventive agents have recently been used for cancer treatment in combination with chemotherapeutics or radiotherapy, uncov-ering a novel strategy for cancer therapy. This strategy opens a new avenue fromcancer prevention to cancer treatment. In vitro and in vivo studies have demon-strated that chemopreventive agents could enhance the antitumor activity of chemotherapeutics, improving the treatment outcome. Growing evidence has shown that chemopreventive agents potentiate the efficacy of chemotherapy and radiotherapy through the regulation of multiple signaling pathways, including Akt, NF-κB, c-Myc, cyclooxygenase-2, apoptosis, and others, suggesting a multitargeted nature of chemopreventive agents. However, further in-depth mecha-nistic studies, in vivo animal experiments, and clinical trials are needed to investi-gate the effects of chemopreventive agents in combination treatment of cancer with conventional cancer therapies. More potent natural and synthetic chemo-preventive agents are also needed to improve the efficacy of mechanism-based and targeted therapeutic strategies against cancer, which are likely to make a significant impact on saving lives. Here, we have briefly reviewed the role of chemopreventive agents in cancer prevention, but most importantly, we have reviewed how they could be useful for cancer therapy in combination with con-ventional therapies.

  7. 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.

  8. Tea beverage in chemoprevention and chemotherapy of prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Imtiaz A SIDDIQUI; Mohammad SALEEM; Vaqar M ADHAMI; Mohammad ASIM; Hasan MUKHTAR

    2007-01-01

    Prostate cancer (Pca) is the most frequently diagnosed malignancy and the sec-ond leading cause of cancer-related deaths in American males with similar trends in many western countries. The existing treatment approaches and surgical inter-vention have not been able to effectively cope with this dreaded disease. For these reasons, it is necessary to intensify our efforts for a better understanding of the disease process and for the development of novel approaches for its preven-tion and treatment. Based on considerable evidence from in vivo and in vitro data and epidemiological studies, in recent years the beverage tea has gained consid-erable attention for reducing the risk of several cancers. Much of the cancerpreventive effects of tea, especially green tea appear to be mediated by the polyphe-nols present therein. Geographical evidence suggests that the incidence and occurrence of Pca is lower in populations that consume tea regularly. This evi-dence suggests that tea polyphenols could be extrapolated to optimize their chemopreventive properties against Pca. Pca represents an excellent candidate disease for chemoprevention because it is typically diagnosed in men over 50 years of age and therefore, even a modest delay in neoplastic development achieved through pharmacological or nutritional intervention could result in a substantial reduction in the incidence of clinically detectable disease. In this review we address the issue of possible use of tea, especially green tea, for the prevention aswell as treatment of Pca.

  9. Terpenoids as potential chemopreventive and therapeutic agents in liver cancer.

    Science.gov (United States)

    Thoppil, Roslin J; Bishayee, Anupam

    2011-09-27

    Despite significant advances in medicine, liver cancer, predominantly hepatocellular carcinoma remains a major cause of death in the United States as well as the rest of the world. As limited treatment options are currently available to patients with liver cancer, novel preventive control and effective therapeutic approaches are considered to be reasonable and decisive measures to combat this disease. Several naturally occurring dietary and non-dietary phytochemicals have shown enormous potential in the prevention and treatment of several cancers, especially those of the gastrointestinal tract. Terpenoids, the largest group of phytochemicals, traditionally used for medicinal purposes in India and China, are currently being explored as anticancer agents in clinical trials. Terpenoids (also called "isoprenoids") are secondary metabolites occurring in most organisms, particularly plants. More than 40 000 individual terpenoids are known to exist in nature with new compounds being discovered every year. A large number of terpenoids exhibit cytotoxicity against a variety of tumor cells and cancer preventive as well as anticancer efficacy in preclinical animal models. This review critically examines the potential role of naturally occurring terpenoids, from diverse origins, in the chemoprevention and treatment of liver tumors. Both in vitro and in vivo effects of these agents and related cellular and molecular mechanisms are highlighted. Potential challenges and future directions involved in the advancement of these promising natural compounds in the chemoprevention and therapy of human liver cancer are also discussed. PMID:21969877

  10. 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.

  11. The role of aspirin in colorectal cancer chemoprevention.

    Science.gov (United States)

    Singh Ranger, Gurpreet

    2016-08-01

    Considerable interest has emerged over the last decade regarding the role of aspirin in prevention of colorectal cancer. This disease is one of the commonest cancers in the Western World, therefore, the existence of a simple "everyday" agent, which could have the ability to prevent the disease, represents an invaluable opportunity clinicians may be able to exploit. Evidence from case-control and cohort studies, and recent updates of randomised controlled trials have been very encouraging-indicating benefit from long term use of aspirin at low dose. Possible mechanisms of chemoprevention include inhibition of the cyclooxygenase (COX) pathway, or COX-independent mechanisms, for example, the PIK3CA pathway, or therapy-induced senescence of cancer cells. The most serious side effect of prolonged aspirin treatment is haemorrhage, especially from the GI tract. This is likely to be less of a problem with chemoprevention at lower doses. One also needs to consider the impact if aspirin resistance, an increasingly recognised clinical entity. PMID:27289249

  12. Chemoprevention of prostate cancer: current status and future directions.

    Science.gov (United States)

    Lieberman, Ronald

    2002-01-01

    Prostate cancer chemoprevention can be described as the administration of natural products and pharmaceutical agents that inhibit one or more steps in the natural history of prostatic carcinogenesis. The principle components of the chemoprevention strategy are closely connected to this natural history and include: (a) agents and their molecular targets; (b) strategic intermediate endpoint biomarkers (IEBs) and their critical pathways; (c) cohorts identified by genetic and acquired risk factors and (d) efficient designs that combine these elements into a cohesive clinical trial. The primary goal is to find effective noncytotoxic agents that modulate the promotion and progression from normal epithelium to dysplasia to high-grade prostatic intraepithelial neoplasia (HGPIN) to locally invasive cancer and metastatic disease. Another important target for chemoprevention is to modulate progression to clinically aggressive disease and to maintain an androgen-sensitive clinical state and delay the emergence of androgen resistance. There is a rationale for use of antiandrogens as the lead class, e.g., 5 alpha receptor inhibitors (5ARI), for chemoprevention of prostate cancer. Nevertheless, the desire to improve the therapeutic index, achieve synergy (5ARI may have only modest anticancer effects) and prevent the emergence of drug (androgen) resistance provide incentives for developing other effective agents and combinations. The availability of more than a dozen classes of noncytotoxic pharmaceutical and natural products already in clinical development create many opportunities for rational combination therapy. Several agent classes have a pharmacodynamic basis for combination with antiandrogens including antiproliferatives, selective estrogen receptor modulators (SERMs), proapoptotic antioxidant micronutrients and selective cyclo-oxygenase (COX)-2 inhibitors. Many other rational pharmacodynamic combinations without antiandrogens are feasible. It is anticipated that in the

  13. Repurposing old drugs to chemoprevention: the case of metformin.

    Science.gov (United States)

    Heckman-Stoddard, Brandy M; Gandini, Sara; Puntoni, Matteo; Dunn, Barbara K; DeCensi, Andrea; Szabo, Eva

    2016-02-01

    Multiple epidemiologic studies have documented an association between the anti-diabetic agent metformin and reduced cancer incidence and mortality. However, this effect has not been consistently demonstrated in animal models or more recent epidemiological studies. The purpose of this paper is to examine metformin's chemopreventive potential by reviewing relevant mechanisms of action, preclinical evidence of efficacy, updated epidemiologic evidence after correction for potential biases and confounders, and recently completed and ongoing clinical trials. Although repurposing drugs with well described mechanisms of action and safety profiles is an appealing strategy for cancer prevention, there is no substitute for well executed late phase clinical trials to define efficacy and populations that are most likely to benefit from an intervention. PMID:26970131

  14. 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.

  15. Women victims of sexual violence: adherence to chemoprevention of HIV.

    Science.gov (United States)

    Diniz, Normélia Maria Freire; de Almeida, Lílian Conceição Guimarães; dos S Ribeiro, Bárbara Cristina; de Macêdo, Valéria Góes

    2007-01-01

    This study aimed to investigate the adherence of women victims of sexual violence, to AIDS chemoprevention treatment. A quantitative study was carried out at a care service to victims of sexual violence in Salvador (Bahia, Brazil). Study participants were 172 women. Data were collected through interviews with forms and consultation of patient files. The results showed that 45.4% of the abused women were teenagers and 40.7% of the attended women were raped. Only 54% of the women were advised to use antiretrovirals to prevent HIV. Adherence to treatment occurred in 57.4% of cases and discontinuity corresponded to 42.6%. Non-adherence to treatment was attributed to psychological or emotional disorders and non-understanding of the established treatment. Therefore, it is important that professionals pay careful attention in order to perceive the conditions that might increase women's vulnerability to the infection. PMID:17375226

  16. Chemopreventive drugs: Mechanisms via inhibition of cancer stem cells in colorectal cancer

    OpenAIRE

    Kim, Tae Il

    2014-01-01

    Recent epidemiological studies, basic research and clinical trials on colorectal cancer (CRC) prevention have helped identify candidates for effective chemopreventive drugs. However, because of the conflicting results of clinical trials or side effects, the effective use of chemopreventive drugs has not been generalized, except for patients with a high-risk for developing hereditary CRC. Advances in genetic and molecular technologies have highlighted the greater complexity of carcinogenesis, ...

  17. Chemoprevention of chemical-induced skin cancer by Panax ginseng root extract

    OpenAIRE

    Sharma, Jyoti; Pradeep K. Goyal

    2015-01-01

    Background Cancer has emerged as a major health problem globally as a consequence to the increased longevity of the population, changing the environment and life style. Chemoprevention is a new and promising strategy for reducing cancer burden. Recently, some natural products have been identified for their chemopreventive activity to reduce the cancer incidence. Ginseng is known for its potential to treat various ailments in human beings. The present study was designed to explore the anticanc...

  18. About the Chemopreventive Agent Development Research Group | Division of Cancer Prevention

    Science.gov (United States)

    The Chemopreventive Agent Development Research Group promotes and supports research on early chemopreventive agent development, from preclinical studies to phase I clinical trials. The group’s projects aim to identify and develop prevention agents with the potential to block, reverse, or delay the early stages of cancer. The overarching goal is to determine positive and negative predictive values of preclinical models for clinical development. |

  19. Biomarker and animal models for assessment of retinoid efficacy in cancer chemoprevention

    Institute of Scientific and Technical Information of China (English)

    Richard M NILES

    2007-01-01

    Vitamin A is essential for normal growth and development. Epidemiology and laboratory studies suggest that decreased vitamin A levels and defective metabo-lisrn/action may contribute to the genesis of certain cancers. Based on this information, natural and synthetic derivatives of vitamin A (retinoids) have been used for chemoprevention of cancer. Retinoids have had some success in the chemoprevention of leukoplakia and in the decreased incidence of second prima-ties in head and neck cancer. There is little information on biomarkers that can be used to assess the efficacy of the chemopreventive activity of retinoids. The ability of retinoids to induce RARb has been consistently shown to correlate with the response of cells and tissues to retinoic acid, but few other biomarkers have been certified as indicators of retinoid activity. In light of the failure of the ATBC and CARET clinical intervention trials for chemoprevention of lung cancer, greater use of animal models for chemoprevention studies is necessary. The potential combination of phytochemicals that inhibit DNA methyltransferase activity with retinoids holds promise for more effective chemoprevention of retinoid-unrespon-sive premalignant lesions.

  20. Nanoencapsulation of pomegranate bioactive compounds for breast cancer chemoprevention

    Directory of Open Access Journals (Sweden)

    Shirode AB

    2015-01-01

    Full Text Available Amit B Shirode,1,2,* Dhruba J Bharali,3,* Sameera Nallanthighal,1,2 Justin K Coon,1,2 Shaker A Mousa,3 Ramune Reliene1,2 1Department of Environmental Health Sciences, University at Albany, State University of New York, Albany, NY, USA; 2Cancer Research Center, University at Albany, Rensselaer, NY, USA; 3Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY, USA *These authors contributed equally to this work Abstract: 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

  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. Spicing up a vegetarian diet: chemopreventive effects of phytochemicals.

    Science.gov (United States)

    Lampe, Johanna W

    2003-09-01

    Thousands of chemical structures have been identified in plant foods. Many are found in spices. Typically, spices are the dried aromatic parts of plants-generally the seeds, berries, roots, pods, and sometimes leaves-that mainly, but not invariably, grow in hot countries. Given the wide range of botanical species and plant parts from which spices are derived, they can contribute significant variety and complexity to the human diet. In the past, the medicinal uses of spices and herbs were often indistinguishable from their culinary uses, and for good reason: people have recognized for centuries both the inherent value, as well as the potential toxicity, of phytochemicals in relation to human health. Plants have the capacity to synthesize a diverse array of chemicals, and understanding how phytochemicals function in plants may further our understanding of the mechanisms by which they benefit humans. In plants, these compounds function to attract beneficial and repel harmful organisms, serve as photoprotectants, and respond to environmental changes. In humans, they can have complementary and overlapping actions, including antioxidant effects, modulation of detoxification enzymes, stimulation of the immune system, reduction of inflammation, modulation of steroid metabolism, and antibacterial and antiviral effects. Embracing a cuisine rich in spice, as well as in fruit and vegetables, may further enhance the chemopreventive capacity of one's diet. PMID:12936952

  3. Cancer chemopreventive and therapeutic activities of red ginseng.

    Science.gov (United States)

    Xiaoguang, C; Hongyan, L; Xiaohong, L; Zhaodi, F; Yan, L; Lihua, T; Rui, H

    1998-02-01

    Red ginseng extract A and B are the active components of Panax ginseng. Red ginseng is a classical traditional Chinese medicine. Among Chinese herbs, red ginseng has been considered as one of the tonics. Many studies indicated that red ginseng could enhance immune function of the human body. The effects of red ginseng extracts on transplantable tumors, proliferation of lymphocyte, two-stage model and rat liver lipid peroxidation were studied. In a two-stage model, red ginseng extracts had a significant cancer chemoprevention. At 50-400 mg/kg, they could inhibit DMBA/Croton oil-induced skin papilloma in mice, decrease the incidence of papilloma, prolong the latent period of tumor occurrence and reduce tumor number per mouse in a dose-dependent manner. Red ginseng extract B could effectively inhibit the Fe2+/cysteine-induced lipid peroxidation of rat liver microsome, suggesting that red ginseng extract B has a stronger antioxidative effect than that of extract A. The results indicated that red ginseng extracts (50 approximately 400 mg/kg) could significantly inhibit the growth of transplantable mouse sarcoma S180 and melanoma B16. Red ginseng extracts A (0.5 mg/ml) and B (0.1 and 0.25 mg/ml) might effectively promote the transformation of T lymphocyte, but there was no influence on lymphocyte proliferation stimulated by concanavalin A. This suggests that red ginseng extracts have potent tumor therapeutic activity and improve the cell immune system. PMID:9533434

  4. Advances in prostate cancer chemoprevention: a translational perspective.

    Science.gov (United States)

    Nambiar, Dhanya; Singh, Rana P

    2013-01-01

    Chemopreventive interventions are steadily emerging as an important aspect of cancer management and control. Herein, we have discussed the major epidemiological and clinical studies advocating the role of androgen inhibitors, flavonoids and antioxidants in preventing prostate cancer (PCa). Androgen inhibitors have lately been discussed not only in treatment of PCa, but also as preventive agents especially after trials with Finasteride and Dutasteride. Flavonoids such as silibinin, green tea polyphenols, genistein, curcumin have shown great promise, but avenues to improve their bioavailability are requisite. Agents with antioxidant potentials like lycopene, selenium, and vitamin E have also been explored. Antioxidant trials have yielded mixed results or benefitted only a subgroup of population, although further studies are needed to establish them as preventive agent. Although a majority of the trials resulted in positive outcomes supporting their role as preventive agents; one should be cautious of neutral or negative results as well. For clinical applicability of these agents, we need to identify the ideal target population, time of intervention, appropriate dosage, and extent of intervention required. Incoherency of data with these agents urges for a stringent study design and thorough interpretation to accurately judge the necessity and feasibility of the preventive measures. PMID:23682779

  5. Molecular targets of cancer chemoprevention by garlic-derived organosulfides

    Institute of Scientific and Technical Information of China (English)

    Anna HERMAN-ANTOSIEWICZ; Anna A POWOLNY; Shivendra V SINGH

    2007-01-01

    The medicinal benefits of Allium vegetables, especially garlic, have been noted throughout recorded history. The known health benefits of Allium vegetables and their constituents include cardiovascular protective effects, stimulation of immune function, reduction of blood glucose level, radioprotection, improvement of memory loss, protection against microbial, viral and fungal infections, as well as anticancer effects. Population-based case control studies have suggested an inverse correlation between dietary intake of Allium vegetables and the risk of different types of cancers. The anticarcinogenic effect of Allium vegetables in-eluding garlic is attributed to organosulfur compounds (OSC), which are highly effective in affording protection against cancer in animal models induced by a variety of chemical carcinogens. More recent studies have shown that certain naturally occurring OSC analogues can suppress proliferation of cancer cells in culture and in vivo. The OSC-induced changes in the proliferation of cancer Cellsare frequently associated with perturbations in cell cycle progression and induc-tion of G2/M phase arrest. The OSC have also been demonstrated to induce apoptosis via the intrinsic pathway by altering the ratio of the Bc1-2 family of proteins both in cell culture and in in vivo models. Anti-angiogenic activity for garlic-derived OSC has also been documented. This article summarizes current knowledge on molecular targets of cancer chemoprevention by OSC.

  6. Cost-effectiveness of prostate cancer chemoprevention among high-risk men.

    Science.gov (United States)

    Zeliadt, Steven B; Ramsey, Scott D

    2010-10-01

    EVALUATION OF: Earnshaw SR, McDade CL, Black LK, Bell CF, Kattan MW. Cost effectiveness of 5-α reductase inhibitors for the prevention of prostate cancer in multiple patient populations. Pharmacoeconomics 28(6), 489-505 (2010). Chemoprevention with 5-α reductase inhibitors (5ARIs) has been shown in clinical trials to reduce the incidence of prostate cancer. Although avoiding or delaying a diagnosis of prostate cancer through chemoprevention is attractive, it is unknown whether 5ARI chemoprevention reduces the number of prostate cancer deaths. Prior cost-effectiveness studies have found the adoption of 5ARIs in the general population to not be cost effective owing to the high costs of 5ARIs and multiple years of treatment required before gains are realized. The current study examines the cost-effectiveness of 5ARIs for men with multiple risk factors, including an elevated prostate-specific antigen and a prior negative biopsy. The analysis consistently observes under multiple assumptions that chemoprevention in the subgroup of high-risk men is cost effective and represents a good value for money, while chemoprevention among men from the general population appears to not be cost effective. PMID:20950065

  7. 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. PMID:26692176

  8. Cancer Prevention and Interception: A New Era for Chemopreventive Approaches.

    Science.gov (United States)

    Albini, Adriana; DeCensi, Andrea; Cavalli, Franco; Costa, Alberto

    2016-09-01

    At several recent, internationally attended scientific meetings, including the American Association for Cancer Research (AACR)'s "Shaping the Future of Cancer Prevention: A Roadmap for Integrative Cancer Science and Public Health" summit in Leesburg (VA) and the AACR Annual Meeting in New Orleans, the focus on cancer prevention to reduce cancer-related deaths was extensively discussed with renewed attention and emphasis. Cancer prevention should be actively proposed even to healthy individuals, and not just to individuals with high cancer risk. We discuss evaluation of a high cancer risk versus the relatively low risk for side effects of chemopreventive agents. The concept of cancer interception, which is halting transformed cells from becoming malignant cancers, should be adopted for cancer prevention. Potential prevention/interception actions include adopting healthy life style and avoiding carcinogens, repressing inflammation and pathologic angiogenesis, controlling metabolism, correcting insulin resistance and other metabolic alterations. Current drugs with limited toxicity can be repurposed to reduce cancer incidence. Aspirin is now being recommended for the prevention of colorectal cancer and it prevents other neoplasms as well. Metformin and β-blockers could be valuable for reducing pancreatic and breast cancer onset. On the basis of the evaluation of cancer risk, we here call for personalized approaches for cancer prevention and preventive interception and we envisage a list of measures and potential guidelines for preventive and interceptive strategies to reduce cancer burden. Investment into translational research to bring these approaches into public health policies and in the clinic is urgently needed. Clin Cancer Res; 22(17); 4322-7. ©2016 AACR. PMID:27220959

  9. Chemopreventive Agents from Physalis minima Function as Michael Reaction Acceptors

    Science.gov (United States)

    Men, Ruizhi; Li, Ning; Ding, Chihong; Tang, Yingzhan; Xing, Yachao; Ding, Wanjing; Ma, Zhongjun

    2016-01-01

    Background: The fruits of some varieties of genus Physalis have been used as delicious fruits and functional food in the Northeast of China. Materials and Methods: To reveal the functional material basis, we performed bioactivity-guided phytochemical research and chemopreventive effect assay of the constituents from Physalis minima. Results: It was demonstrated that the ethyl acetate extract of P. minima L. (EEPM) had potential quinone reductase (QR) inducing activity with induction ratio (IR, QR induction activity) value of 1.47 ± 0.24, and glutathione binding property as potential Michael reaction acceptors (with an α, β-unsaturated ketone moiety). Furthermore, bioactivity-guided phytochemical research led eight compounds (1–8), which were elucidated as 3-isopropyl-5-acetoxycyclohexene-2-one-1 (1), isophysalin B (2), physalin G (3), physalin D (4), physalin I (5), physordinose B (6), stigmasterol-3-O-β-D-glucopyranoside (7) and 5α-6β-dihydroxyphysalin R (8) on the basis of nuclear magnetic resonance spectroscopy analyses and HRESIMS. Then, isophysalin B (2) and physordinose B (6) showed significant QR inducing activity with IR value of 2.80 ± 0.19 and 2.38 ± 0.46, respectively. SUMMARY An ultra-performance liquid chromatographic method with glutathione as the substrate was used to detect the Michael reaction acceptors in extracts of Physalis minima (EPM)We investigated the chemical constituents of EPM guided by biological activity methodIsophysalin B (1) and physordinose B (6) showed strong quinone reductase inducing activity with induction ratio values of 2.80 ± 0.19 and 2.38 ± 0.46This study generated useful information for consumers and many encourage researchers to utilize edible fruits from Physalis as a source of phytochemicals Abbreviations used: EPM: Extracts of Physalis minima, EEPM: Ethyl acetate extract of Physalis minima L., GSH: Glutathione, MRAs: Michael reaction acceptors, QR: Quinone reductase. PMID:27279713

  10. Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer

    Science.gov (United States)

    Malik, Arshi; Afaq, Farrukh; Sarfaraz, Sami; Adhami, Vaqar M.; Syed, Deeba N.; Mukhtar, Hasan

    2005-01-01

    Prostate cancer is the most common invasive malignancy and the second leading cause of cancer-related deaths among U.S. males, with a similar trend in many Western countries. One approach to control this malignancy is its prevention through the use of agents present in diet consumed by humans. Pomegranate from the tree Punica granatum possesses strong antioxidant and antiinflammatory properties. We recently showed that pomegranate fruit extract (PFE) possesses remarkable antitumor-promoting effects in mouse skin. In this study, employing human prostate cancer cells, we evaluated the antiproliferative and proapoptotic properties of PFE. PFE (10-100 μg/ml; 48 h) treatment of highly aggressive human prostate cancer PC3 cells resulted in a dose-dependent inhibition of cell growth/cell viability and induction of apoptosis. Immunoblot analysis revealed that PFE treatment of PC3 cells resulted in (i) induction of Bax and Bak (proapoptotic); (ii) down-regulation of Bcl-XL and Bcl-2 (antiapoptotic); (iii) induction of WAF1/p21 and KIP1/p27; (iv) a decrease in cyclins D1, D2, and E; and (v) a decrease in cyclin-dependent kinase (cdk) 2, cdk4, and cdk6 expression. These data establish the involvement of the cyclin kinase inhibitor-cyclin-cdk network during the antiproliferative effects of PFE. Oral administration of PFE (0.1% and 0.2%, wt/vol) to athymic nude mice implanted with androgen-sensitive CWR22Rν1 cells resulted in a significant inhibition in tumor growth concomitant with a significant decrease in serum prostate-specific antigen levels. We suggest that pomegranate juice may have cancer-chemopreventive as well as cancer-chemotherapeutic effects against prostate cancer in humans. PMID:16192356

  11. Chemopreventive Effect of Aerosolized Polyphenon E on Lung Tumorigenesis in A/J Mice

    Directory of Open Access Journals (Sweden)

    Ying Yan

    2007-05-01

    Full Text Available Effective chemoprevention of lung cancer in high-risk patients through the administration of pharmacologic or nutritional agents is urgently needed. Aerosol inhalation can deliver chemopreventive agents directly to the respiratory tract to inhibit the tumorigenic process. In this study, polyphenon E (PolyE and (-epigallocatechin-3-gal late (EGCG were administered by aerosol delivery to A/J mice beginning 2 weeks after carcinogen treatment and continuing daily by inhalation throughout the remainder of the study (20 weeks. PolyE decreased tumor load by ∼ 59%. However, EGCG, both at the same dose and at a higher dose, failed to inhibit lung carcinogenesis. These results indicate that aerosol delivery of PolyE, but not EGCG, may be a useful chemopreventive protocol in subjects at high risk for lung cancer.

  12. Oral chemoprevention with acetyl salicylic Acid, vitamin d and calcium reduces the risk of tobacco carcinogen-induced bladder tumors in mice

    DEFF Research Database (Denmark)

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

    2013-01-01

    , and diet with chemoprevention (acetyl salicylic acid, 1-alpha 25(0H)2-vitamin D3 and calcium). There were significantly fewer tumors (0 (0-0) vs. 0 (0-2), p = .045) and fewer animals with tumors (0/20 vs. 5/20, p = .045) in the chemoprevention group compared with controls. Thus, chemoprevention diet...

  13. Chemopreventive effect of Lagenaria siceraria in two stages DMBA plus croton oil induced skin papillomagenesis.

    Science.gov (United States)

    Kumar, Navneet; Kale, Raosaheb K; Tiku, Ashu B

    2013-01-01

    Cancer chemoprevention is a dietary or therapeutic strategy to prevent, suppress, or delay carcinogenesis either at initiation or progression level with nontoxic agents. Use of natural dietary compounds has been a major chemopreventive approach to modulate tumorigenic pathways. In the present study, we have evaluated Lagenaria siceraria (bottle gourd), a common vegetable of Indian household for its chemomodulatory potential. The fruit has been used in traditional medicine for a very long time for health benefits and to cure pain, ulcers, fever, cough, asthma, and other bronchial disorders. However, despite its reported beneficial effect the chemo modulatory potential of this plant has not been reported. Therefore chemopreventive effect of bottle gourd juice (BGJ) was studied against 7,12-dimethylbenz(a)anthracene (DMBA) plus croton oil induced skin papillomagenesis in Swiss albino mice. The effect was studied both at antiinitiation and antiinitiation/promotion level followed by histopathological study. A dose of 2.5% and 5% given in drinking water showed significant decrease in papilloma number, papilloma incidence, papilloma multiplicity, papilloma latency, papilloma volume, and papilloma size in different size range. Histopathological study showed chemopreventive effect by minimizing loss of stratification, a decrease in number of epithelial layers, reducing dermal infiltration and protection for various cytoplasmic changes. Higher dose of BGJ was found to be more effective than lower dose and the chemopreventive effect was maximum for antiinitiation/promotion treatment. Altogether, this study reports the chemopreventive effect of Lagenaria siceraria on skin papillomagenesis for the first time and suggests that its consumption may help in suppression of skin cancer. PMID:23914728

  14. 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. PMID:26608291

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

    Science.gov (United States)

    Dietary nutrients with ability to reverse adverse epigenetic events have great potential for cancer chemoprevention. 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-d...

  17. Azoxymethane-induced rat aberrant crypt foci: Relevance in studying chemoprevention of colon cancer

    Institute of Scientific and Technical Information of China (English)

    Jayadev Raju

    2008-01-01

    The pathogenesis of colon cancer involves sequential and multistep progression of epithelial cells initiated to a cancerous state with defined precancerous intermediaries.Aberrant crypt foci (ACF) represent the earliest identifiable intermediate precancerous lesions during colon carcinogenesis in both laboratory animals and humans.ACF are easily induced by colon-specific carcinogens in rodents and can be used to learn more about the process of colon carcinogenesis.For over two decades,since its first discovery,azoxymethane(AOM)-induced rodent ACF have served as surrogate biomarkers in the screening of various anticarcinogens and carcinogens.Several dietary constituents and phytochemicals have been tested for their colon cancer chemopreventive efficacy using the ACF system.There has been substantial effort in defining and refining ACF in terms of understanding their molecular make-up,and extensive research in this field is currently in progress.In chemoprevention studies,AOM-induced rat ACF have been very successful as biomarkers,and have provided several standardized analyses of data.There have been several studies that have reported that ACF data do not correlate to actual colon tumor outcome,however,and hence there has been an ambiguity about their role as biomarkers.The scope of this mini-review is to provide valuable insights and limitations of AOM-induced rat ACF as biomarkers in colon cancer chemoprevention studies.The role of the dynamics and biological heterogeneity of ACF is critical in understanding them as biomarkers in chemoprevention studies.

  18. Acteoside-mediates chemoprevention of experimental liver carcinogenesis through STAT-3 regulated oxidative stress and apoptosis.

    Science.gov (United States)

    Peerzada, Kaiser J; Faridi, Aamir H; Sharma, Love; Bhardwaj, Subhash C; Satti, Naresh K; Shashi, Bhushan; Tasduq, Sheikh A

    2016-07-01

    In the absence of an effective therapy against Hepatocellular Carcinoma (HCC), chemoprevention remains an important strategy to circumvent morbidity and mortality. Here, we examined chemopreventive potential of Acteoside (ACT), a plant derived phenylethanoid glycoside against an environmental and dietary carcinogen, diethylnitrosamine (DEN)-induced rat hepatocarcinogenesis. ACT treatment (0.1 and 0.3% supplemented with diet) started 2 weeks before DEN challenge and continued for 18 weeks thereafter, showed a remarkable chemopreventive activity. ACT treatment resulted in reduced HCC nodules. Histopathology showed progressive tissue damage, necrosis (5 weeks), hepatocytic injury (10 weeks), anisonucleosis with presence of prominent nucleoli, sinusidal dilations, and lymphomono nuclear inflammation (18 weeks). Biochemical analysis showed hepatocytic injury (raised ALT, p reactive oxygen species (ROS) levels and prevented mitochondrial membrane potential (MMP) loss. Immunoblotting showed ACT treatment reversed DEN-induced NF-κB, Bax, Cytochrome C, Bcl-2, and Stat-3 levels. We conclude that chemoprotective effect of ACT is mediated by STAT-3 dependent regulation of oxidative stress and apoptosis and ACT has potential to be developed as a chemopreventive agent. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 782-798, 2016. PMID:26990576

  19. Preclinical renal cancer chemopreventive efficacy of geraniol by modulation of multiple molecular pathways

    International Nuclear Information System (INIS)

    Graphical abstract: Diagrammatic presentation of the hypothesis of the article in a concise manner. It reveals the chemopreventive efficacy of GOH possibly through the modulation of multiple molecular targets. GOH inhibits ROS generation, NFκB and PCNA expression thereby abrogating inflammation and proliferation of tubular cells of kidney. Whereas, GOH induces effector caspase-3 expression both through mitochondrial signalling pathway and death receptor signalling pathway. Highlights: → Geraniol modulates renal carcinogenesis in Wistar rats. → It abrogates Fe-NTA induced oxidative stress, inflammation and hyperproliferation. → Promotes apoptosis via induction of both mitochondrial and death receptor pathway. → Thus, inhibits renal carcinogenesis by modulating multiple molecular targets. -- Abstract: In the present study, we have evaluated the chemopreventive potential of geraniol (GOH), an acyclic monoterpene alcohol against ferric nitrilotriacetate (Fe-NTA) induced renal oxidative stress and carcinogenesis in Wistar rats. Chronic treatment of Fe-NTA induced oxidative stress, inflammation and cellular proliferation in Wistar rats. The chemopreventive efficacy of GOH was studied in terms of xenobiotic metabolizing enzyme activities, LPO, redox status, serum toxicity markers and the expression of putative nephrotoxicity biomarker Kim-1, tumor suppressor gene P53, inflammation, cell proliferation and apoptosis related genes in the kidney tissue. Oral administration of GOH at doses of 100 and 200 mg/kg b wt effectively suppressed renal oxidative stress and tumor incidence. Chemopreventive effects of GOH were associated with upregulation of xenobiotic metabolizing enzyme activities and down regulation of serum toxicity markers. GOH was able to down regulate expression of Kim-1, NFκB, PCNA, P53 along with induction of apoptosis. However, higher dose of GOH was more effective in modulating these multiple molecular targets both at transcriptional and protein

  20. 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.

  1. Molecular mechanisms underlying chemopreventive potential of curcumin: Current challenges and future perspectives.

    Science.gov (United States)

    Kumar, Gaurav; Mittal, Sonam; Sak, Katrin; Tuli, Hardeep Singh

    2016-03-01

    In recent years, natural compounds have received considerable attention in preventing and curing most dreadful diseases including cancer. The reason behind the use of natural compounds in chemoprevention is associated with fewer numbers of side effects than conventional chemotherapeutics. Curcumin (diferuloylmethane, PubMed CID: 969516), a naturally occurring polyphenol, is derived from turmeric, which is used as a common Indian spice. It governs numerous intracellular targets, including proteins involved in antioxidant response, immune response, apoptosis, cell cycle regulation and tumor progression. A huge mass of available studies strongly supports the use of Curcumin as a chemopreventive drug. However, the main challenge encountered is the low bioavailability of Curcumin. This extensive review covers various therapeutic interactions of Curcumin with its recognized cellular targets involved in cancer treatment, strategies to overcome the bioavailability issue and adverse effects associated with Curcumin consumption. PMID:26876915

  2. Chronic unpredictable stress deteriorates the chemopreventive efficacy of pomegranate through oxidative stress pathway.

    Science.gov (United States)

    Hasan, Shirin; Suhail, Nida; Bilal, Nayeem; Ashraf, Ghulam Md; Zaidi, Syed Kashif; AlNohair, Sultan; Banu, Naheed

    2016-05-01

    Chronic unpredictable stress (CUS) can influence the risk and progression of cancer through increased oxidative stress. Pomegranate is known to protect carcinogenesis through its anti-oxidative properties. This study is carried out to examine whether CUS affects the chemopreventive potential of pomegranate through oxidative stress pathway. Role of CUS on early stages of 7, 12 dimethyl benz(a) anthracene (DMBA) induced carcinogenesis, and its pre-exposure effect on chemopreventive efficacy of pomegranate juice (PJ) was examined in terms of in vivo antioxidant and biochemical parameters in Swiss albino rats. Rats were divided in various groups and were subjected to CUS paradigm, DMBA administration (65 mg/kg body weight, single dose), and PJ treatment. Exposure to stress (alone) and DMBA (alone) led to increased oxidative stress by significantly decreasing the antioxidant enzymes activities and altering the glutathione (GSH), malondialdehyde (MDA), glutamate oxaloacetate transaminase (GOT), and glutamate pyruvate transaminase (GPT) levels. A significant increase in DNA damage demonstrated by comet assay was seen in the liver cells. Stress exposure to DMBA-treated rats further increased the oxidative stress and disturbed the biochemical parameters as compared to DMBA (alone)-treated rats. Chemoprevention with PJ in DMBA (alone)-treated rats restored the altered parameters. However, in the pre-stress DMBA-treated rats, the overall antioxidant potential of PJ was significantly diminished. Our results indicate that chronic stress not only increases the severity of carcinogenesis but also diminishes the anti-oxidative efficacy of PJ. In a broader perspective, special emphasis should be given to stress management and healthy diet during cancer chemoprevention. PMID:26596837

  3. Injectable Sustained Release Microparticles of Curcumin: A New Concept for Cancer Chemoprevention

    OpenAIRE

    Shahani, Komal; Swaminathan, Suresh Kumar; Freeman, Diana; Blum, Angela; Ma, Linan; Panyam, Jayanth

    2010-01-01

    Poor oral bioavailability limits the use of curcumin and other dietary polyphenols in the prevention and treatment of cancer. Minimally invasive strategies that can provide effective and sustained tissue concentrations of these agents will be highly valuable tools in the fight against cancer. The objective of this study was to investigate the use of an injectable sustained release microparticle formulation of curcumin as a novel approach to breast cancer chemoprevention. A biodegradable and b...

  4. STAT3 as a chemoprevention target in carcinogen-induced head and neck squamous cell carcinoma.

    OpenAIRE

    Peyser, ND; Wang, L.; Zeng, Y.; Acquafondata, M.; Freilino, ML; Li, H.; M. Sen; Gooding, WE; Satake, M; Wang, Z.; Johnson; Grandis, JR

    2016-01-01

    Head and neck squamous cell carcinoma (HNSCC) is a frequently fatal disease due in large part to a high rate of second primary tumor (SPT) formation. The 4-nitroquinoline 1-oxide (4-NQO) mouse model of oral carcinogenesis provides a robust system in which to study chemopreventive agents in the context of chemically-induced HNSCC tumors. Signal transducer and activator of transcription 3 (STAT3) is a potent oncogene that is hyperactivated by tyrosine phosphorylation early in HNSCC carcinogenes...

  5. Chemopreventive Effects of RXR-Selective Rexinoid Bexarotene on Intestinal Neoplasia of ApcMin/+ Mice

    OpenAIRE

    Janakiram, Naveena B; Altaf Mohammed; Li Qian; Chang-In Choi; Steele, Vernon E.; Rao, Chinthalapally V.

    2012-01-01

    Retinoid X receptor (RXR) has been implicated in several neoplastic diseases. Previously, we have shown that RXR-α is downregulated in human and rodent colonic tumors, suggesting a potential target for colon cancer prevention (http://www.cancer.org/Cancer/ColonandRectumCancer/DetailedGuide/colorectal-cancer-key-statistics). Experiments were designed to assess the chemopreventive efficacy of the selective RXR agonist bexarotene for the suppression of intestinal tumorigenesis in ApcMin/+ mice. ...

  6. Targeting specific cell signaling transduction pathways by dietary and medicinal phytochemicals in cancer chemoprevention

    International Nuclear Information System (INIS)

    Natural phytochemicals derived from dietary sources or medicinal plants have gained significant recognition in the potential management of several human clinical conditions. Much research has also been geared towards the evaluation of plant extracts as effective prophylactic agents since they can act on specific and/or multiple molecular and cellular targets. Plants have been an abundant source of highly effective phytochemicals which offer great potential in the fight against cancer by inhibiting the process of carcinogenesis through the upregulation of cytoprotective genes that encode for carcinogen detoxifying enzymes and antioxidant enzymes. The mechanistic insight into chemoprevention further includes induction of cell cycle arrest and apoptosis or inhibition of signal transduction pathways mainly the mitogen-activated protein kinases (MAPK), protein kinases C (PKC), phosphoinositide 3-kinase (PI3K), glycogen synthase kinase (GSK) which lead to abnormal cyclooxygenase-2 (COX-2), activator protein-1 (AP-1), nuclear factor-kappaB (NF-κB) and c-myc expression. Effectiveness of chemopreventive agents reflects their ability to counteract certain upstream signals that leads to genotoxic damage, redox imbalances and other forms of cellular stress. Targeting malfunctioning molecules along the disrupted signal transduction pathway in cancer represent a rational strategy in chemoprevention. NF-κB and AP-1 provide mechanistic links between inflammation and cancer, and moreover regulate tumor angiogenesis and invasiveness, indicating that signaling pathways that mediate their activation provide attractive targets for new chemotherapeutic approaches. Thus cell signaling cascades and their interacting factors have become important targets of chemoprevention and phenolic phytochemicals and plant extracts seem to be promising in this endeavor.

  7. Participation of Asian-American Women in Cancer Chemoprevention Research: Physician Perspectives

    OpenAIRE

    Nguyen, Tung T.; Somkin, Carol P.; Ma, Yifei

    2005-01-01

    To the authors’ knowledge, little is known regarding the participation of Asian Americans in cancer prevention research. In 2002, the authors mailed surveys to primary care physicians in Northern California to assess their knowledge, attitudes, behaviors, and barriers concerning the participation of Asian-American women in breast cancer chemoprevention research. The response rate was 52.3% (n = 306 physicians). For physician barriers, most respondents selected lack of study knowledge (73%) an...

  8. CHEMOPREVENTIVE POTENTIAL OF CARALLUMA ADSCENDENS (ROXB.) AGAINST 1,2 DIMETHYL HYDRAZINE INDUCED COLON CARCINOGENESIS

    OpenAIRE

    Gowri S; Chinnaswamy, P.; Suganthi. V.

    2013-01-01

    Colorectal cancer is increasingly common nowadays in Asian countries and still remains the second leading cause of cancer death in the United States. The chemopreventive and hypolipidemic effect of Caralluma adscendens (Roxb.), an edible succulent, was studied in 1,2-dimethylhydrazine (DMH)-induced colon cancer. Rats were given a weekly subcutaneous injection of DMH (20 mg/kg body weight), a known colon carcinogen, in the groin for 16 weeks. Caralluma adscendens (Roxb.) (50 & 100 mg/kg body w...

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

    OpenAIRE

    Nur Özten-Kandas; Bosland, Maarten C.

    2011-01-01

    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 appl...

  10. Can Transcriptomics Provide Insight into the Chemopreventive Mechanisms of Complex Mixtures of Phytochemicals in Humans?

    OpenAIRE

    van Breda, Simone G.J.; Wilms, Lonneke C.; Gaj, Stan; Jennen, Danyel G.J.; Briedé, Jacob J.; Helsper, Johannes P.; Kleinjans, Jos C.S.; de Kok, Theo M.C.M.

    2014-01-01

    Blueberries contain relatively large amounts of different phytochemicals, which are suggested to have chemopreventive properties, but little information is available on the underlying molecular modes of action. This study investigates whole genome gene expression changes in lymphocytes of 143 humans after a 4-week blueberry-apple juice dietary intervention. Differentially expressed genes and genes correlating with the extent of antioxidant protection were identified in four subgroups. The mag...

  11. Co-chemoprevention of Mouse Lung Tumors by SAHA and Atorvastatin

    OpenAIRE

    Pereira, Michael A.; Warner, Blake M.; Knobloch, Thomas J.; Weghorst, Christopher M.; Lubet, Ronald A.; Steele, Vernon E; Casto, Bruce C.

    2012-01-01

    Atorvastatin and SAHA were evaluated for co-chemoprevention of mouse lung tumors. In Experiment 1, lung tumors were induced by vinyl carbamate in strain A/J mice followed by 500 mg/kg SAHA, 60 or 180 mg/kg Atorvastatin, and combinations containing SAHA and Atorvastatin administered in their diet. SAHA and both combinations, but not Atorvastatin, decreased the multiplicity of lung tumors, including large adenomas and adenocarcinomas with the combinations demonstrating the greatest efficacy. In...

  12. Evaluation of anti-inflammatory, immunomodulatory, chemopreventive and wound healing potentials from Schinus terebinthifolius methanolic extract

    OpenAIRE

    Lis E.S. Fedel-Miyasato; Cândida A.L. Kassuya; Sarah A. Auharek; Anelise S. N. Formagio; Cardoso, Claudia A. L.; Mariana O. Mauro; Andréa L. Cunha-Laura; Antônio C.D. Monreal; MARIA C. VIEIRA; Rodrigo J. Oliveira

    2014-01-01

    Inflammatory and genetic alterations are related to the development of chronic diseases such as cancer. Schinus terebinthifolius Raddi, Anacardiaceae, is used in folk medicine to treat inflammation, wounds and tumors. This study evaluated the anti-inflammatory, immunomodulatory, chemopreventive, and wound healing potentials of the methanolic extract from the leaves of Schinus terebinthifolius. The chemical composition of the extract was characterized using preliminary analytical LC methods. T...

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

    OpenAIRE

    Zhiyu Zhang; Chunhao Yu; Chun-Feng Zhang; Xiao-Hui Wu; Xiao-Dong Wen; Samantha Anderson; Wei Du; Wei-Hua Huang; Shao-Ping Li; Chong-Zhi Wang; Chun-Su Yuan

    2014-01-01

    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 co...

  14. Molecular Mechanisms of Silibinin-Mediated Cancer Chemoprevention with Major Emphasis on Prostate Cancer

    OpenAIRE

    Ting, Harold; Deep, Gagan; Agarwal, Rajesh

    2013-01-01

    Despite advances in early detection, prostate cancer remains the second highest cancer mortality in American men, and even successful interventions are associated with enormous health care costs as well as prolonged deleterious effects on quality of patient life. Prostate cancer chemoprevention is one potential avenue to alleviate these burdens. It is a regime whereby long-term treatments are intended to prevent or arrest cancer development, in contrast to more direct intervention upon diseas...

  15. Going Green: The Role of the Green Tea Component EGCG in Chemoprevention

    OpenAIRE

    Schramm, Laura

    2013-01-01

    Tea is one of the most consumed beverages worldwide, and green tea is the least processed from the buds of the Camellia sinensis plant. The most abundant component of green tea is (−)-epigallocatechin-3-gallate (EGCG), which has been the focus of many cell culture, animal and clinical trials, revealing that EGCG possesses antiproliferative, antimutagenic, antioxidant, antibacterial, antiviral and chemopreventive effects. In this review we briefly summarize the mechanism of action(s) of the gr...

  16. Notes from the Field: “Green” Chemoprevention as Frugal Medicine

    OpenAIRE

    Fahey, Jed W.; Talalay, Paul; Kensler, Thomas W.

    2012-01-01

    Prevention trials of whole foods or simple extracts offer prospects for reducing an expanding global burden of cancer effectively and, in contrast to promising isolated phytochemicals or pharmaceuticals, frugally. We use the term “green chemoprevention” to differentiate a food-centered approach that is sustainable in underserved populations. It can be applied to personalized medicine just as well as can a pharmaceutical approach, but only green chemoprevention can be applied in both rich and ...

  17. Polyamines as mediators of APC-dependent intestinal carcinogenesis and cancer chemoprevention

    OpenAIRE

    Rial, Nathaniel S; Meyskens, Frank L.; Gerner, Eugene W.

    2009-01-01

    Combination chemoprevention for cancer was proposed a quarter of a century ago, but has not been implemented in standard medical practice owing to limited efficacy and toxicity. Recent trials have targeted inflammation and polyamine biosynthesis, both of which are increased in carcinogenesis. Preclinical studies have demonstrated that DFMO (difluoromethylornithine), an irreversible inhibitor of ODC (ornithine decarboxylase) which is the first enzyme in polyamine biosynthesis, combined with NS...

  18. Anthocyans from fruits and vegetables--does bright colour signal cancer chemopreventive activity?

    Science.gov (United States)

    Cooke, Darren; Steward, William P; Gescher, Andreas J; Marczylo, Tim

    2005-09-01

    Consumption of fruits and berries has been associated with decreased risk of developing cancer. The most abundant flavonoid constituents of fruits and berries are anthocyans (i.e. anthocyanins, glycosides, and their aglycons, anthocyanidins) that cause intense colouration. In this review, we describe epidemiological evidence hinting at the cancer preventive activity of anthocyan-containing foods in humans, results of chemoprevention studies in rodent models with anthocyans or anthocyan-containing fruit/vegetable extracts, and pharmacological properties of anthocyans. Anthocyanidins have been shown to inhibit malignant cell survival and confound many oncogenic signalling events in the 10(-6)-10(-4) M concentration range. Studies of the pharmacokinetics of anthocyanins after their consumption as single agents, anthocyanin mixtures or berry extracts suggest that anthocyanins reach levels of 10(-8)-10(-7) M in human blood. It is unclear whether such concentrations are sufficient to explain anticarcinogenic effects, and whether anthocyanins exert chemopreventive efficacy themselves, or if they need to undergo hydrolysis to their aglyconic counterparts. The currently available literature provides tantalising hints of the potential usefulness of anthocyans or anthocyan mixtures as cancer chemopreventive interventions. Nevertheless further studies are necessary to help adjudge the propitiousness of their clinical development. PMID:16084717

  19. Novel aspects for the application of Curcumin in chemoprevention of various cancers.

    Science.gov (United States)

    Bachmeier, Beatrice E; Killian, Peter; Pfeffer, Ulrich; Nerlich, Andreas G

    2010-01-01

    Chemoprevention of malignant tumor growth is a novel and potentially powerful approach for tumor therapy. Recent in vitro and in vivo investigations provide increasing evidence that naturally occurring substances may exhibit significant chemopreventive activities. To this regard, the spice Curcumin, widely used in Indian cuisine, has been identified to show considerable anti-tumor effects. Most interestingly, numerous studies have not shown toxic side effects of this substance. Curcumin induces tumor cell apoptosis along with a reduction of tumor cell invasion and metastasis. Recent molecular studies provide evidence that Curcumin acts via a control of the NFkappaB pathway exerting most of the various modulating and moderating effects on malignant cells. Along with these in vitro studies, ex vivo and first clinical investigations confirm the anti-tumor effects of Curcumin, either as an isolated chemoprevention substance or in combination with chemotherapeutic agents as supportive measure reducing pharmaceutical resistance of tumor cells to certain chemotherapeutics. Despite our increasing knowledge on this interesting substance there still remain many unknown effects that deserve intense investigation. PMID:20036978

  20. Capsaicin: A novel chemopreventive molecule and its underlying molecular mechanisms of action

    Directory of Open Access Journals (Sweden)

    A A Oyagbemi

    2010-01-01

    Full Text Available Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide is the a principal pungent ingredient of hot red and chili peppers that belong to the plant genus Capsicum (Solanaceae. Capsaicin is a cancer-suppressing agent. It blocks the translocation of nuclear factor kappa B (NF-kB, activator protein 1 (AP-1, and signal transducer and activator of transcription (STAT3 signaling pathway that are required for carcinogenesis. The anti-inflammatory potential of capsaicin is attributed to its inhibitory effect on inducible COX-2 mRNA expression. Cytochrome P4502E1 mediates the activation of xenobiotics such as vinyl carbamate and dimethyl nitrosamine to their toxic metabolites. This metabolic activation of xenobiotics by Cytochrome P4502E1 has been shown to be inhibited by capsaicin. Capsaicin also generates reactive oxygen species in cells with resultant induction of apoptosis and cell cycle arrest, which is beneficial for cancer chemoprevention. Therefore, the use of capsaicin as a chemopreventive agent is of immense benefit for cancer chemoprevention. The search strategy included printed journals, pubmed, and medline, using the terms ′capsaicin′ and ′anticancer′ citations, relevant to anticancer properties of capsaicin.

  1. Chemopreventive effect of Quercus infectoria against chemically induced renal toxicity and carcinogenesis

    Directory of Open Access Journals (Sweden)

    Muneeb U Rehman

    2012-06-01

    Full Text Available In this study we have shown that Quercus infectoria attenuates Fe- NTA induced renal oxidative stress, hyperproliferative response and renal carcinogenesis in rats. Fe-NTA promoted DEN (N-diethyl nitrosamine initiated renal carcinogenesis by increasing the percentage incidence of tumors and induces early tumor markers viz. ornithine decarboxylase (ODC level and PCNA expression. Fe- NTA (9 mg Fe/kg body weight, intraperitoneally enhances renal Malondialdehyde, xanthine oxidase and hydrogen peroxide generation with reduction in renal glutathione content, antioxidant enzymes, viz., glutathione peroxidase, glutathione reductase, catalase, glucose-6-phosphate dehydrogenase and phase-II metabolizing enzymes such as glutathione-S-transferase and quinone reductase. It also enhances blood urea nitrogen and serum creatinine. Fe-NTA also lead to increase in levels of some inflammatory markers viz NO and MPO and some proinflammatory cytokines viz PGE-2 and TNF-1. The chemopreventive efficacy of Quercus infectoria was studied in terms of xenobiotic metabolizing enzyme activities, LPO, redox status, serum toxicity markers, inflammatory and proinflammatory markers and cell proliferation in the kidney tissue. Oral administration of Quercus infectoria at doses of 75 and 150 mg/kg b wt effectively suppressed renal oxidative stress, inflammation and tumor incidence. Chemopreventive effects of Quercus infectoria were associated with up-regulation of xenobiotic metabolizing enzyme activities and down regulation of serum toxicity markers. Present study supports Quercus infectoria as a potent chemopreventive agent and suppresses Fe-NTA-induced renal carcinogenesis and oxidative and inflammatory response in Wistar rat.

  2. Multitargeted Low-Dose GLAD Combination Chemoprevention: A Novel and Promising Approach to Combat Colon Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Altaf Mohammed

    2013-05-01

    Full Text Available Preclinical studies have shown that gefitinib, licofelone, atorvastatin, and α-difluoromethylornithine (GLAD are promising colon cancer chemopreventive agents. Because low-dose combination regimens can offer potential additive or synergistic effects without toxicity, GLAD combination was tested for toxicity and chemopreventive efficacy for suppression of intestinal tumorigenesis in adenomatous polyposis coli (APCMin/+ mice. Six-week-old wild-type and APCMin/+ mice were fed modified American Institute of Nutrition 76A diets with or without GLAD (25 + 50 + 50 + 500 ppm for 14 weeks. Dietary GLAD caused no signs of toxicity based on organ pathology and liver enzyme profiles. GLAD feeding strongly inhibited (80–83%, P 95% fewer polyps with sizes of >2 mm compared with control mice and showed 75% and 85% inhibition of colonic tumors in males and females, respectively. Molecular analyses of polyps suggested that GLAD exerts efficacy by inhibiting cell proliferation, inducing apoptosis, decreasing β-catenin and caveolin-1 levels, increasing caspase-3 cleavage and p21, and modulating expression profile of inflammatory cytokines. These observations demonstrate that GLAD, a novel cocktail of chemopreventive agents at very low doses, suppresses intestinal tumorigenesis in APCMin/+ mice with no toxicity. This novel strategy to prevent colorectal cancer is an important step in developing agents with high efficacy without unwanted side effects.

  3. Chemopreventive effects of the polyunsaturated fatty acids omega-3 on the carcinogenesis process of the upper aerodigestive tract induced by 4-nitroquinoline-1-oxide in Swiss mice

    OpenAIRE

    Gama, Ricardo Ribeiro; Allan GIOVANINI; de Rosa, Fernanda Scarmato; Ogata, Daniel Cury; de Oliveira, André Luiz Vettore; Cardoso Costa, Ana Flávia; Talini, Carolina; Feniman, Denise; Kamei, Douglas; Júnior, Celso Felipe; Coco, Allan; Carvalho, André Lopes

    2014-01-01

    Objective: To study the potential chemopreventive effects of polyunsaturated fatty acids omega-3 in Swiss mice submitted to oral and oesophageal carcinogenesis induction by 4-nitroquinoline-1-oxide (4-NQO). Study design: The animals underwent carcinogenesis induction with 50 µg/mL 4-NQO for eight weeks. The animals were divided into groups: Group I—4-NQO induction without chemoprevention, Group II—chemoprevention with the addition of 5% fish oil (FO) in their diet after 4-NQO carcinogenesis i...

  4. 5-aminosalicylic acid is an attractive candidate agent for chemoprevention of colon cancer in patients with inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Yang Cheng; Pierre Desreumaux

    2005-01-01

    Inflammatory bowel disease (IBD) is classically subdivided into ulcerative colitis (UC) and Crohn's disease (CD). Patients with IBD have increased risk for colorectal cancer. Because the pathogenesis of colorectal carcinoma has not been entirely defined yet and there is no ideal treatment for colon cancer, cancer prevention has become increasingly important in patients with IBD. The two adopted methods to prevent the development of colon cancer in clinical practice include the prophylactic colectomy and colonoscopic surveillance.But patients and physicians seldom accept colectomy as a routine preventive method and most patients do not undergo appropriate colonoscopic surveillance. Chemoprevention refers to the use of natural or synthetic chemical agents to reverse, suppress, or to delay the process of carcinogenesis.Chemoprevention is a particularly useful method in the management of patients at high risk for the development of specific cancers based on inborn genetic susceptibility, the presence of cancer-associated disease, or other known risk factors. Prevention of colorectal cancer by administration of chemopreventive agents is one of the most promising options for IBD patients who are at increased risks of the disease. The chemopreventive efficacy of nonsteroidal antiinflammatory drugs (NSAIDs) against intestinal tumors has been well established. But with reports that NSAIDs aggravated the symptoms of colitis, their sustained use for the purpose of cancer chemoprevention has been relatively contraindicated in IBD patients. Another hopeful candidate chemoprevention drug for IBD patients is 5-aminosalicylic acid (5-ASA), which is well tolerated by most patients and has limited systemic adverse effects, and no gastrointestinal toxicity. 5-ASA lacks the well-known side effects of longterm NSAIDs use. Retrospective correlative studies have suggested that the long-term use of 5-ASA in IBD patients may significantly reduce the risk of development of colorectal cancer

  5. 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. PMID:19508900

  6. Antiproliferative and cancer-chemopreventive properties of sulfated glycosylated extract derived from Leucaena leucocephala

    Directory of Open Access Journals (Sweden)

    Gamal-Eldeen Amira

    2007-01-01

    Full Text Available This work aimed to prove that simple chemical modification could provide new cancer chemopreventive and/or anticancer properties to the inactive extracted polysaccharide derived from Leucaena leucocephala . Polysaccharides were extracted from Leucaena leucocephala seeds and its 2,4-pentanedione-treated derivative (glycosylated form was prepared, which is further sulphated to give sulphated glycosylated form. Estimation of their anti-initiation activity, modulation of carcinogen metabolism, was indicated by the inhibition cytochrome P450 1A (CYP1A and the induction of glutathione-S-transferases (GSTs. Anti-proliferation activity was investigated by MTT assay against human hepatocarcinoma (HepG2, breast carcinoma (MCF-7 and lymphoblastic leukemia (1301. Apoptosis/necrosis and cell cycle were analyzed by flow cytometry. The results revealed that glycosylated form inhibited both CYP1A and GSTs, while sulphated glycosylated form not only inhibited CYP1A, but also induced the GSTs. Unlike GE, sulphated glycosylated form possessed a significant anti-proliferative activity against different cell lines. Analysis of HepG2 cell cycle phases demonstrated that glycosylated form led to a delay of G2/M-phase, while sulphated glycosylated form led to a concomitant arrest in S- and G2/M-phases. Investigation of apoptosis/necrosis ratio demonstrated that both of glycosylated form and sulphated glycosylated form induced HepG2 cell death by necrosis, but not apoptosis. Unmodified crude extract was neither active as cancer chemopreventive nor as anti-proliferative. In conclusion, chemical modification of Leucaena gum induced its cancer chemopreventive and anti-proliferative activities.

  7. In vitro cancer chemopreventive properties of polysaccharide extract from the brown alga, Sargassum latifolium.

    Science.gov (United States)

    Gamal-Eldeen, Amira M; Ahmed, Eman F; Abo-Zeid, Mona A

    2009-06-01

    Polysaccharides of edible algae attracted extensive interest due to their numerous biological activities. Sargassum latifolium (Turner) C. Agardh, belongs to Sargassaceae, is a brown algae in red sea shores in Egypt. This work is a novel attempt to explore the cancer chemopreventive activity of different fractions of water-soluble polysaccharide extract derived from S. latifolium. Estimation of cancer chemopreventive activity, specifically anti-initiation, including the modulation of carcinogen metabolism and the antioxidant capacity, revealed that E1 and E4 were potent anti-initiators, where they lead not only to an inhibition in the carcinogen activator cytochrome P450 1A (IC50 2.54 and 10.30 microg/ml, respectively), but also to an induction in the carcinogen detoxification enzymes glutathione-S-transferases (144% and 225% of the control, respectively). E1 and E4 inhibited 59% and 63% of the induced-DNA damage, as measured by comet assay. Similarly both E1 and E4 possessed potential anti-promoting properties as indicated by their anti-inflammatory activity. E1 and E4 enhanced the macrophage proliferation; however they dramatically inhibited the stimulated NO (30.7% and 59.3%), TNF-alpha (38.2% and 54.9) and COX-2 (20% and 18%), respectively. E3 showed a selective cytotoxicity against lymphoblastic leukemia (1301 cells), while other fraction extracts had no cytotoxic effect against all tested cell lines. E3 led to a major disturbance in cell cycle including arrest in both S-phases in 1301 cells. This disturbance was associated with an induced-cell death due to apoptosis, but not necrosis. In conclusion, E1 and E4 are promising cancer chemopreventive fractions, since they had tumor anti- initiating activity via their protective modulation of carcinogen metabolism, and tumor anti-promoting activity via their anti-inflammatory activity, while E3 can be considered as a promising anti-cancer agent against leukemia. PMID:19306910

  8. 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.

  9. Chemoprevention of Lung Squamous Cell Carcinoma in Mice by a Mixture of Chinese Herbs

    OpenAIRE

    Wang, Yian; Zhang, Zhongqiu; Garbow, Joel R.; Rowland, Doug J.; Ronald A Lubet; Sit, Daniel; Law, Frances; You, Ming

    2009-01-01

    Anti-tumor B (ATB) is a Chinese herbal mixture of six plants. Previous studies have shown significant chemopreventive efficacy of ATB against human esophageal and lung cancers. We have recently developed a new mouse model for lung squamous cell carcinomas (SCC). In this study, lung SCC mouse model was characterized using small-animal imaging techniques (MRI and CT). ATB decreased lung SCC significantly (3.1 fold, p < 0.05) and increased lung hyperplastic lesions by 2.4 fold (p < 0.05). This o...

  10. Cancer chemoprevention by phytochemicals. Expectation for phytochemicals as preventive agents against radiation-induced carcinogenesis

    International Nuclear Information System (INIS)

    There is growing evidence from the studies using animal models that phytochemicals in plants have preventive effect on cancer induction, which is mediated by polyphenol anti-oxidative and anti-inflammatory functions. Some phytochemicals such as curcumin and epigallocatechin gallate have been moved onto clinical trials. These phytochemicals are also expected to reduce the deleterious effect of radiation, and to be a powerful tool for the prevention of radiation carcinogenesis. In this review, we summarized the general concept of cancer chemoprevention and usefulness of phytochemicals as cancer preventive agents, and pointed out their possibilities for prevention of radiation-induced carcinogenesis. (author)

  11. Curcumin as a therapeutic agent in the chemoprevention of inflammatory bowel disease.

    Science.gov (United States)

    Sreedhar, Remya; Arumugam, Somasundaram; Thandavarayan, Rajarajan A; Karuppagounder, Vengadeshprabhu; Watanabe, Kenichi

    2016-05-01

    Inflammatory bowel diseases (IBD), mainly Crohn's disease (CD) and ulcerative colitis (UC) are chronic ailments of the gastrointestinal tract, characterized by recurrent inflammation. Current therapeutic strategies are based on the mitigation of symptoms, including inflammatory remission and healing of mucosal manifestations. Extensive studies have suggested that continuous oxidative damage can lead to the inflammatory signaling cascade in IBD. Curcumin, a potent modulator of cell signaling, is popular for its antioxidant and anti-inflammatory activities, and has already been shown remarkable therapeutic results in IBD. Here, we review and discuss the effects of curcumin as a therapeutic agent in the chemoprevention of IBD. PMID:26995272

  12. Natural products as a source of potential cancer chemotherapeutic and chemopreventive agents.

    Science.gov (United States)

    Cassady, J M; Baird, W M; Chang, C J

    1990-01-01

    Recent advances in the chemistry of novel bioactive natural products are reported. This research is directed to the exploration of plants with confirmed activity in bioassays designed to detect potential cancer chemotherapeutic and chemopreventive agents. Structural work and chemical studies are reported for several cytotoxic agents from the plants Annona densicoma, Annona reticulata, Claopodium crispifolium, Polytrichum obioense, and Psorospermum febrifugum. Studies are also reported based on development of a mammalian cell culture benzo[a]pyrene metabolism assay for the detection of potential anticarcinogenic agents from natural products. In this study a number of isoflavonoids and flavonoids with antimutagenic activity have been discovered. PMID:2189947

  13. Steroidal pyrazolines evaluated as aromatase and quinone reductase-2 inhibitors for chemoprevention of cancer.

    Science.gov (United States)

    Abdalla, Mohamed M; Al-Omar, Mohamed A; Bhat, Mashooq A; Amr, Abdel-Galil E; Al-Mohizea, Abdullah M

    2012-05-01

    The aromatase and quinone reductase-2 inhibition of synthesized heterocyclic pyrazole derivatives fused with steroidal structure for chemoprevention of cancer is reported herein. All compounds were interestingly less toxic than the reference drug (Cyproterone(®)). The aromatase inhibitory activities of these compounds were much more potent than the lead compound resveratrol, which has an IC(50) of 80 μM. In addition, all the compounds displayed potent quinone reductase-2 inhibition. Initially the acute toxicity of the compounds was assayed via the determination of their LD(50). The aromatase and quinone reductase-2 inhibitors resulting from this study have potential value in the treatment and prevention of cancer. PMID:22361454

  14. Chemopreventive effect of PSP through targeting of prostate cancer stem cell-like population.

    Science.gov (United States)

    Luk, Sze-Ue; Lee, Terence Kin-Wah; Liu, Ji; Lee, Davy Tak-Wing; Chiu, Yung-Tuen; Ma, Stephanie; Ng, Irene Oi-Lin; Wong, Yong-Chuan; Chan, Franky Leung; Ling, Ming-Tat

    2011-01-01

    Recent evidence suggested that prostate cancer stem/progenitor cells (CSC) are responsible for cancer initiation as well as disease progression. Unfortunately, conventional therapies are only effective in targeting the more differentiated cancer cells and spare the CSCs. Here, we report that PSP, an active component extracted from the mushroom Turkey tail (also known as Coriolus versicolor), is effective in targeting prostate CSCs. We found that treatment of the prostate cancer cell line PC-3 with PSP led to the down-regulation of CSC markers (CD133 and CD44) in a time and dose-dependent manner. Meanwhile, PSP treatment not only suppressed the ability of PC-3 cells to form prostaspheres under non-adherent culture conditions, but also inhibited their tumorigenicity in vivo, further proving that PSP can suppress prostate CSC properties. To investigate if the anti-CSC effect of PSP may lead to prostate cancer chemoprevention, transgenic mice (TgMAP) that spontaneously develop prostate tumors were orally fed with PSP for 20 weeks. Whereas 100% of the mice that fed with water only developed prostate tumors at the end of experiment, no tumors could be found in any of the mice fed with PSP, suggesting that PSP treatment can completely inhibit prostate tumor formation. Our results not only demonstrated the intriguing anti-CSC effect of PSP, but also revealed, for the first time, the surprising chemopreventive property of oral PSP consumption against prostate cancer. PMID:21603625

  15. Chemopreventive effects of cardamom (Elettaria cardamomum L.) on chemically induced skin carcinogenesis in Swiss albino mice.

    Science.gov (United States)

    Qiblawi, Samir; Al-Hazimi, Awdah; Al-Mogbel, Mohammed; Hossain, Ashfaque; Bagchi, Debasis

    2012-06-01

    The chemopreventive potential of cardamom was evaluated on 7,12-dimethylbenz[a]anthracene-initiated and croton oil-promoted mouse skin papillomagenesis. A significant reduction in the values of tumor incidence, tumor burden, and tumor yield and the cumulative number of papillomas was observed in mice treated orally with 0.5 mg of cardamom powder in suspension continuously at pre-, peri-, and post-initiational stages of papillomagenesis compared with the control group. The average weight and diameter of tumors recorded were also comparatively lower in the cardamom-treated mouse group. Treatment of cardamom suspension by oral gavage for 15 days resulted in a significant decrease in the lipid peroxidation level of the liver (P < .01). In addition, the reduced glutathione level was significantly elevated in comparison with the control group (P < .05) following cardamom suspension treatment. Taken together, these findings indicate the potential of cardamom as a chemopreventive agent against two-stage skin cancer. PMID:22404574

  16. Updates and Controversies in the Rapidly Evolving Field of Lung Cancer Screening, Early Detection, and Chemoprevention

    Directory of Open Access Journals (Sweden)

    Hasmeena Kathuria

    2014-05-01

    Full Text Available Lung cancer remains the leading cause of cancer-related death in the United States. Cigarette smoking is a well-recognized risk factor for lung cancer, and a sustained elevation of lung cancer risk persists even after smoking cessation. Despite identifiable risk factors, there has been minimal improvement in mortality for patients with lung cancer primarily stemming from diagnosis at a late stage when there are few effective therapeutic options. Early detection of lung cancer and effective screening of high-risk individuals may help improve lung cancer mortality. While low dose computerized tomography (LDCT screening of high risk smokers has been shown to reduce lung cancer mortality, the high rates of false positives and potential for over-diagnosis have raised questions on how to best implement lung cancer screening. The rapidly evolving field of lung cancer screening and early-detection biomarkers may ultimately improve the ability to diagnose lung cancer in its early stages, identify smokers at highest-risk for this disease, and target chemoprevention strategies. This review aims to provide an overview of the opportunities and challenges related to lung cancer screening, the field of biomarker development for early lung cancer detection, and the future of lung cancer chemoprevention.

  17. 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.

  18. Chemopreventive and therapeutic potentials of thymoquinone in HepG2 cells: mechanistic perspectives.

    Science.gov (United States)

    ElKhoely, Abeer; Hafez, Hafez F; Ashmawy, Abeer M; Badary, Osama; Abdelaziz, Ahmed; Mostafa, Adel; Shouman, Samia A

    2015-07-01

    Liver cancer is the fifth commonest malignancy worldwide and the third leading cause of death. Identifying novel curative and preventive therapy may improve its prognosis. In this study, thymoquinone (TQ), the most active biological ingredient of Nigella sativa Linn, was investigated for its antitumor activity. Mechanistic perspectives underlying this antitumor activity were explored by testing its effect on cell cycle, apoptosis, and angiogenesis. In addition, the chemopreventive effect of TQ was carried out by measuring its effect on phase I CYP1A1 and phase II glutathione S-transferase (GST) drug-metabolizing enzymes. The results of the present study revealed the effectiveness of TQ as an antitumor agent against different types of cancer including brain, colon, cervix and liver at both a time- and concentration-dependent manner. In HepG2 cells, it induced G2/M phase cell cycle arrest and a concentration-dependent increase in the percentage of apoptotic cells with an increase in the ratio of Bax/BCL-2. Moreover, the expression of mRNA and protein level of vascular endothelial growth factor decreased as the concentration of TQ increased. Our data showed a significant inhibition of induced phase I CYP1A1 enzyme, and elevation in the content of glutathione and activity of phase II enzyme GST, in HepG2 cells. Our results provide support for the beneficial use of TQ as a therapeutic and chemopreventive agent against liver cancer. PMID:25796541

  19. 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.

  20. 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

    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

  1. 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

  2. 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

  3. Acceptability by community health workers in Senegal of combining community case management of malaria and seasonal malaria chemoprevention

    DEFF Research Database (Denmark)

    Tine, Roger Ck; Ndiaye, Pascal; Ndour, Cheikh T;

    2013-01-01

    Community case management of malaria (CCMm) and seasonal malaria chemoprevention (SMC) are anti-malarial interventions that can lead to substantial reduction in malaria burden acting in synergy. However, little is known about the social acceptability of these interventions. A study was undertaken...... to assess whether combining the interventions would be an acceptable approach to malaria control for community health workers (CHWs)....

  4. 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.

  5. Cancer chemoprevention and nutriepigenetics: state of the art and future challenges.

    Science.gov (United States)

    Gerhauser, Clarissa

    2013-01-01

    The term "epigenetics" refers to modifications in gene expression caused by heritable, but potentially reversible, changes in DNA methylation and chromatin structure. Epigenetic alterations have been identified as promising new targets for cancer prevention strategies as they occur early during carcinogenesis and represent potentially initiating events for cancer development. Over the past few years, nutriepigenetics - the influence of dietary components on mechanisms influencing the epigenome - has emerged as an exciting new field in current epigenetic research. During carcinogenesis, major cellular functions and pathways, including drug metabolism, cell cycle regulation, potential to repair DNA damage or to induce apoptosis, response to inflammatory stimuli, cell signalling, and cell growth control and differentiation become deregulated. Recent evidence now indicates that epigenetic alterations contribute to these cellular defects, for example epigenetic silencing of detoxifying enzymes, tumor suppressor genes, cell cycle regulators, apoptosis-inducing and DNA repair genes, nuclear receptors, signal transducers and transcription factors by promoter methylation, and modifications of histones and non-histone proteins such as p53, NF-κB, and the chaperone HSP90 by acetylation or methylation.The present review will summarize the potential of natural chemopreventive agents to counteract these cancer-related epigenetic alterations by influencing the activity or expression of DNA methyltransferases and histone modifying enzymes. Chemopreventive agents that target the epigenome include micronutrients (folate, retinoic acid, and selenium compounds), butyrate, polyphenols from green tea, apples, coffee, black raspberries, and other dietary sources, genistein and soy isoflavones, curcumin, resveratrol, dihydrocoumarin, nordihydroguaiaretic acid (NDGA), lycopene, anacardic acid, garcinol, constituents of Allium species and cruciferous vegetables, including indol-3-carbinol

  6. Molecular mechanisms of chemopreventive effects of selected dietary and medicinal phenolic substances.

    Science.gov (United States)

    Surh, Y

    1999-07-16

    Recently, considerable attention has been focused on identifying naturally occurring chemopreventive substances capable of inhibiting, retarding, or reversing the multi-stage carcinogenesis. A wide array of phenolic substances, particularly those present in dietary and medicinal plants, have been reported to possess substantial anticarcinogenic and antimutagenic activities. The majority of these naturally occurring phenolics retain antioxidative and anti-inflammatory properties which appear to contribute to their chemopreventive or chemoprotective activity. Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), a pungent ingredient of hot chili pepper, protects against experimentally-induced mutagenesis and tumorigenesis. It also induces apoptosis in various immortalized or malignant cell lines. Plants of ginger family (Zingiberaceae) have been frequently and widely used as spices and also, in traditional oriental medicine. Curcumin, a yellow ingredient from turmeric (Curcuma longa L., Zingiberaceae), has been extensively investigated for its cancer chemopreventive potential. Yakuchinone A [1-(4'-hydroxy-3'-methoxyphenyl)-7-phenyl-3-heptanone] and yakuchinone B [1-(4'-hydroxy-3'-methoxyphenyl)-7-phenylhept-1-en-3-one] present in Alpinia oxyphylla Miquel (Zingiberaceae) have inhibitory effects on phorbol ester-induced inflammation and skin carcinogenesis in mice, and oxidative stress in vitro. These diarylheptanoids suppress phorbol ester-induced activation of ornithine decarboxylase and production of tumor necrosis factor-alpha or interleukin-1alpha and their mRNA expression. They also nullified the phorbol ester-stimulated induction of activator protein 1 (AP-1) in cultured human promyelocytic leukemia (HL-60) cells. In addition, both yakuchinone A and B induced apoptotic death in HL-60 cells. Ginger (Zingiber officinale Roscoe, Zingiberaceae) contains such pungent ingredients as [6]-gingerol and [6]-paradol, which also have anti-tumor promotional and

  7. Statins in the chemoprevention of colorectal cancer in established animal models of sporadic and colitis-associated cancer.

    Science.gov (United States)

    Pikoulis, Emmanouil; Margonis, Georgios A; Angelou, Anastasios; Zografos, George C; Antoniou, Efstathios

    2016-03-01

    Despite the availability of effective surveillance for colorectal cancer with colonoscopy, chemoprevention might be an acceptable alternative. Statins are potent inhibitors of cholesterol biosynthesis. In clinical trials, statins have been found to be beneficial in the primary and secondary prevention of coronary heart disease. However, the overall benefits observed with statins appear to be greater than what might be expected from changes in lipid levels alone, suggesting effects beyond cholesterol lowering. This systematic review aimed to gather information on the possible chemopreventive role of statins in preventing carcinogenesis and tumor promotion by a diverse array of mechanisms in both sporadic and colitis-associated cancer in animal models. The MEDLINE database was thoroughly searched using the following keywords: 'statin, HMG-CoA reductase inhibitor, colon cancer, mice, rats, chemoprevention, colitis-associated cancer'. Additional articles were gathered and evaluated. There are a lot of clinical studies and meta-analyses, as well as a plethora of basic research studies implementing cancer cell lines and animal models, on the chemopreventive role of statins in colorectal cancer (CRC). However, data derived from clinical studies are inconclusive, yet they show a tendency toward a beneficial role of statins against CRC pathogenesis. Thus, more research on the molecular pathways of CRC tumorigenesis as related to statins is warranted to uncover new mechanisms and compare the effect of statins on both sporadic and colitis-associated cancer in animal models. Basic science results could fuel exclusive colitis-associated cancer clinical trials to study the chemopreventive effects of statins and to differentiate between their effects on the two types of CRCs in humans. PMID:25768976

  8. Biomedical Properties of a Natural Dietary Plant Metabolite, Zerumbone, in Cancer Therapy and Chemoprevention Trials

    Directory of Open Access Journals (Sweden)

    Heshu Sulaiman Rahman

    2014-01-01

    Full Text Available Zerumbone (ZER is a naturally occurring dietary compound, present in many natural foods consumed today. The compound derived from several plant species of the Zingiberaceae family that has been found to possess multiple biomedical properties, such as antiproliferative, antioxidant, anti-inflammatory, and anticancer activities. However, evidence of efficacy is sparse, pointing to the need for a more systematic review for assessing scientific evidence to support therapeutic claims made for ZER and to identify future research needs. This review provides an updated overview of in vitro and in vivo investigations of ZER, its cancer chemopreventive properties, and mechanisms of action. Therapeutic effects of ZER were found to be scientifically plausible and could be explained partially by in vivo and in vitro pharmacological activities. Much of the research outlined in this paper will serve as a foundation to explain ZER anticancer bioactivity, which will open the door for the development of strategies in the treatment of malignancies using ZER.

  9. 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. 

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

    International Nuclear Information System (INIS)

    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

  11. 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.

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

    Science.gov (United States)

    Cazzaniga, Massimiliano; Bonanni, Bernardo

    2015-01-01

    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. PMID:26605341

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

    Directory of Open Access Journals (Sweden)

    Takuji Tanaka

    2012-07-01

    Full Text Available 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.

  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. The Chemopreventive Phytochemical Moringin Isolated from Moringa oleifera Seeds Inhibits JAK/STAT Signaling

    Science.gov (United States)

    Weigl, Julia; De Nicola, Gina Rosalinda; Canistro, Donatella; Paolini, Moreno; Iori, Renato; Rascle, Anne

    2016-01-01

    Sulforaphane (SFN) and moringin (GMG-ITC) are edible isothiocyanates present as glucosinolate precursors in cruciferous vegetables and in the plant Moringa oleifera respectively, and recognized for their chemopreventive and medicinal properties. In contrast to the well-studied SFN, little is known about the molecular pathways targeted by GMG-ITC. We investigated the ability of GMG-ITC to inhibit essential signaling pathways that are frequently upregulated in cancer and immune disorders, such as JAK/STAT and NF-κB. We report for the first time that, similarly to SFN, GMG-ITC in the nanomolar range suppresses IL-3-induced expression of STAT5 target genes. GMG-ITC, like SFN, does not inhibit STAT5 phosphorylation, suggesting a downstream inhibitory event. Interestingly, treatment with GMG-ITC or SFN had a limited inhibitory effect on IFNα-induced STAT1 and STAT2 activity, indicating that both isothiocyanates differentially target JAK/STAT signaling pathways. Furthermore, we showed that GMG-ITC in the micromolar range is a more potent inhibitor of TNF-induced NF-κB activity than SFN. Finally, using a cellular system mimicking constitutive active STAT5-induced cell transformation, we demonstrated that SFN can reverse the survival and growth advantage mediated by oncogenic STAT5 and triggers cell death, therefore providing experimental evidence of a cancer chemopreventive activity of SFN. This work thus identified STAT5, and to a lesser extent STAT1/STAT2, as novel targets of moringin. It also contributes to a better understanding of the biological activities of the dietary isothiocyanates GMG-ITC and SFN and further supports their apparent beneficial role in the prevention of chronic illnesses such as cancer, inflammatory diseases and immune disorders. PMID:27304884

  16. The Chemopreventive Effect of Tamoxifen Combined with Celecoxib on DMBA chemically-Induced Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    Xiaoxu Liu; Huafeng Kang; Xijing Wang; Zhijun Dai; Fengjie Xue; Xinghuan Xue

    2007-01-01

    Objective: To investigate the chemopreventive effect of tamoxifen combined with a COX-2 selective inhibitor, celecoxib, on breast cancer in rats chemically induced by 7,12-dimethylben (a)anthracene (DMBA). Methods:DMBA was irrigated into the stomaches of SD female rats to build breast cancer model. A total of 120 rats were divided into four groups: control group, tamoxifen group, celecoxib group and combined group. The incidence rate, latent period, number and volume of breast cancer were detected and analyzed. Results:The tumor incidence rate of tamoxifen group (48.15%, 13/27) and celecoxib group (50.00%,14/28) were lower than that of control group (85.71%, 24/28), but higher than that of combined group (21.43%, 6/28). The tumor's latent period of tamoxifen group (97.54±1.85 d) and celecoxib group (96.79±2.89 d) were longer than that of control group (89.50±5.99 d), but shorter than that of combined group (103.67±3.39 d). The average tumor number of tamoxifen group (1.77±0.73) and celecoxib group (1.71±0.61) were less than that of control group (3.50±1.62), but more than that of combined group ( 1.17±0.42 ). The average tumor volume of tamoxifen group (1.78±0.71 cm3) and celecoxib group (2.05±1.04 cm3) were smaller than that of control group (6.42±3.96 cm3), but bigger than that of combined group (0.71±0.96 cm3) (P < 0.05 respectively).Conclusion:Celecoxib and tamoxifen are effective drugs in preventing the occurrence of rat breast cancer chemically induced by DMBA. Furthermore, combination of them has better chemopreventive effect.

  17. 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, III; 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.

  18. Chemoprevention of aberrant crypt foci in the colon of rats by dietary onion.

    Science.gov (United States)

    Taché, Sylviane; Ladam, Aélis; Corpet, Denis E

    2007-01-01

    Onion intake might reduce the risk of colorectal cancer, according to epidemiology. However, Femia showed in 2003 that diets with a 20% onion intake increase carcinogenesis in rats. We speculated this dose was too high. Prevention of initiation was thus tested in 60 rats given a 5% dried onion diet or AIN76 diet, and initiated 12 days later with azoxymethane (AOM, 1x20 mg/kg i.p.), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ, 2x200 mg/kg p.o.), or N-nitroso-N-methylurea (2x50 mg/kg p.o.). Prevention of promotion was tested in 38 rats given AOM, then randomised to: AIN76 diet; 5% onion diet; phytochemicals diet (supplemented with propyl-disulfide, quercetine-glycosides and oligofructose); 1% pluronic F68 diet (a potent chemopreventive PEG-like block-polymer, used as a positive control). Aberrant crypt foci (ACF) were scored 30 days (initiation) or 100 days (promotion) after carcinogen injection. The onion diet given during initiation reduced the number of AOM-induced ACF (60 versus 86, p=0.03), and the size of IQ-induced ACF (1.33 versus 1.97, p=0.02). Given post-initiation, the onion diet reduced the number of ACF (34 versus 59, p=0.008) and of large ACF (6 versus 15, p=0.02). Phytochemicals diet and pluronic diet reduced ACF growth similarly. Data show that a 5% onion diet reduced carcinogenesis during initiation and promotion stages, and suggest this chemoprevention is due to known phytochemicals. PMID:17188859

  19. Chemopreventive effect of sinapic acid on 1,2-dimethylhydrazine-induced experimental rat colon carcinogenesis.

    Science.gov (United States)

    Balaji, C; Muthukumaran, J; Nalini, N

    2014-12-01

    Sinapic acid (SA) is a naturally occurring phenolic acid found in various herbal plants which is attributed with numerous pharmacological properties. This study was aimed to investigate the chemopreventive effect of SA on 1,2-dimethylhydrazine (DMH)-induced rat colon carcinogenesis. Rats were treated with DMH injections (20 mg kg(-1) bodyweight (b.w.) subcutaneously once a week for the first 4 consecutive weeks and SA (20, 40 and 80 mg kg(-1) b.w.) post orally for 16 weeks. At the end of the 16-week experimental period, all the rats were killed, and the tissues were evaluated biochemically. Our results reveal that DMH alone treatment decreased the levels/activities of lipid peroxidation by-products such as thiobarbituric acid reactive substances, conjugated dienes and antioxidants such as superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase and reduced glutathione in the intestine and colonic tissues which were reversed on supplementation with SA. Moreover, the activities of drug-metabolizing enzymes of phase I (cytochrome P450 and P4502E1) were enhanced and those of phase II (glutathione-S-transferase, DT-diaphorase and uridine diphosphate glucuronosyl transferase) were diminished in the liver and colonic mucosa of DMH alone-treated rats and were reversed on supplementation with SA. All the above changes were supported by the histopathological observations of the rat liver and colon. These findings suggest that SA at the dose of 40 mg kg(-1) b.w. was the most effective dose against DMH-induced colon carcinogenesis, and thus, SA could be used as a potential chemopreventive agent. PMID:24532707

  20. The Chemopreventive Phytochemical Moringin Isolated from Moringa oleifera Seeds Inhibits JAK/STAT Signaling.

    Science.gov (United States)

    Michl, Carina; Vivarelli, Fabio; Weigl, Julia; De Nicola, Gina Rosalinda; Canistro, Donatella; Paolini, Moreno; Iori, Renato; Rascle, Anne

    2016-01-01

    Sulforaphane (SFN) and moringin (GMG-ITC) are edible isothiocyanates present as glucosinolate precursors in cruciferous vegetables and in the plant Moringa oleifera respectively, and recognized for their chemopreventive and medicinal properties. In contrast to the well-studied SFN, little is known about the molecular pathways targeted by GMG-ITC. We investigated the ability of GMG-ITC to inhibit essential signaling pathways that are frequently upregulated in cancer and immune disorders, such as JAK/STAT and NF-κB. We report for the first time that, similarly to SFN, GMG-ITC in the nanomolar range suppresses IL-3-induced expression of STAT5 target genes. GMG-ITC, like SFN, does not inhibit STAT5 phosphorylation, suggesting a downstream inhibitory event. Interestingly, treatment with GMG-ITC or SFN had a limited inhibitory effect on IFNα-induced STAT1 and STAT2 activity, indicating that both isothiocyanates differentially target JAK/STAT signaling pathways. Furthermore, we showed that GMG-ITC in the micromolar range is a more potent inhibitor of TNF-induced NF-κB activity than SFN. Finally, using a cellular system mimicking constitutive active STAT5-induced cell transformation, we demonstrated that SFN can reverse the survival and growth advantage mediated by oncogenic STAT5 and triggers cell death, therefore providing experimental evidence of a cancer chemopreventive activity of SFN. This work thus identified STAT5, and to a lesser extent STAT1/STAT2, as novel targets of moringin. It also contributes to a better understanding of the biological activities of the dietary isothiocyanates GMG-ITC and SFN and further supports their apparent beneficial role in the prevention of chronic illnesses such as cancer, inflammatory diseases and immune disorders. PMID:27304884

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

    International Nuclear Information System (INIS)

    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

  2. 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

  3. Chemopreventive Effect of Cardamom (Elettaria cardamomum L.) Against Benzo(α)Pyrene-Induced Forestomach Papillomagenesis in Swiss Albino Mice.

    Science.gov (United States)

    Qiblawi, Samir; Dhanarasu, Sasikumar; Faris, Mo'ez Al-Islam

    2015-01-01

    Prevention of cancer through dietary intervention has recently gained significant recognition. Cardamom (Elettaria cardamomum), a dietary phytoproduct, is a popular spice that is regularly used as a flavoring agent in various cuisines, and is much valued for its medicinal properties. In the present study, the cancer chemopreventive potential of cardamom was investigated against benzo(α)pyrene [B(α)P]-induced forestomach papillomagenesis in mice. Results showed that treatment with cardamom [(B(α)P + cardamom] reduced tumor incidence and multiplicity significantly (Pcardamom compared with the control. Furthermore, the nonenzymatic antioxidant glutathione was significantly (Pcardamom-treated group, whereas the lipid peroxidation level along with lactate dehydrogenase activity exhibited a significant (Pcardamom treatment compared to the control. These results suggest that cardamom has the potential to become a pivotal chemopreventive agent against forestomach cancer. PMID:26081028

  4. Genotoxicity of the cancer chemopreventive drug candidates CP-31398, SHetA2, and phospho-ibuprofen

    OpenAIRE

    Doppalapudi, Rupa S.; Riccio, Edward S.; Davis, Zoe; Menda, Sean; Wang, Abraham; Du, Nicholas; Green, Carol; Kopelovich, Levy; Rao, Chinthalapally V.; Benbrook, Doris M.; Kapetanovic, Izet M.

    2012-01-01

    The genotoxic activities of three cancer chemopreventive drug candidates, CP-31398 (a cell permeable styrylquinazoline p53 modulator, SHetA2 (a flexible heteroarotinoid), and phospho-ibuprofen (PI, a derivative of ibuprofen) were tested. None of the compounds were mutagenic in the Salmonella/Escherichia coli/microsome plate incorporation test. CP-31398 and SHetA2 did not induce chromosomal aberrations (CA) in Chinese hamster ovary (CHO) cells, either in the presence or absence of rat hepatic ...

  5. Chemopreventive Effects of RXR-Selective Rexinoid Bexarotene on Intestinal Neoplasia of ApcMin/+ Mice1

    OpenAIRE

    Janakiram, Naveena B; Mohammed, Altaf; Qian, Li; Choi, Chang-In; Steele, Vernon E.; Rao, Chinthalapally V.

    2012-01-01

    Retinoid X receptor (RXR) has been implicated in several neoplastic diseases. Previously, we have shown that RXR-α is downregulated in human and rodent colonic tumors, suggesting a potential target for colon cancer prevention (http://www.cancer.org/Cancer/ColonandRectumCancer/DetailedGuide/colorectal-cancer-key-statistics). Experiments were designed to assess the chemopreventive efficacy of the selective RXR agonist bexarotene for the suppression of intestinal tumorigenesis in ApcMin/+ mice. ...

  6. Disruption of androgen and estrogen receptor activity in prostate cancer by a novel dietary diterpene carnosol: implications for chemoprevention

    OpenAIRE

    Jeremy J Johnson; Syed, Deeba N.; Suh, Yewseok; Heren, Chenelle R.; Saleem, Mohammad; Siddiqui, Imtiaz A.; Mukhtar, Hasan

    2010-01-01

    Emerging data is suggesting that estrogens, in addition to androgens, may also be contributing to the development of prostate cancer (PCa). In view of this notion agents that target estrogens, in addition to androgens, may be a novel approach for PCa chemoprevention and treatment. Thus, the identification and development of non-toxic dietary agents capable of disrupting androgen receptor (AR) in addition to estrogen receptor (ER) could be extremely useful in the management of PCa. Through mol...

  7. Modulation of polyamine metabolism as a chemopreventive strategy of phytochemicals in a cell culture model of colorectal cancers

    OpenAIRE

    Ulrich, Sandra

    2007-01-01

    Resveratrol a natural occuring polyphenol present in red wine, peanuts and grapes, has been reported to exhibit a wide range of biological and pharmacological properties. In addition to cardioprotective and antiinflammatory effects, potent chemopreventive activities of resveratrol and its analogs in various carcinogenesis models are described and there has been a great deal of experimental effort directed toward defining these effects. We and others could previously demonstrate that resveratr...

  8. 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.

  9. Mixture of Uncaria and Tabebuia Extracts are Potentially Chemopreventive in CBA/Ca Mice - A Long-term Experiment

    OpenAIRE

    Budán, Ferenc; Szabo, István; Varjas, Timea; Nowrasteh, Ghodratollah; Dávid, Tamás; Gergely, Péter; Varga, Zsuzsa; Molnár, Kornélia; Kádár, Balázs; Orsos, Zsuzsa; Kiss, István; Ember, István

    2010-01-01

    Abstract A long-term experimental animal model was developed by our research group for the evaluation of potential chemopreventive effects. The inhibitory effects of agents on carcinogen (7,12-Dimetilbenz[a]anthracene (DMBA)) induced molecular epidemiological biomarkers, in this case the expression of key onco/suppressor genes were investigated. Expression pattern of c-myc, Ha-ras, Bcl-2, K-ras protoonco and p53 tumoursuppressor genes were studied to elucidate early carcinogenic...

  10. Acyclic retinoid in chemoprevention of hepatocellular carcinoma: Targeting phosphorylated retinoid X receptor-α for prevention of liver carcinogenesis

    Directory of Open Access Journals (Sweden)

    Masahito Shimizu

    2012-01-01

    Full Text Available One of the key features of hepatocellular carcinoma (HCC is the high rate of intrahepatic recurrence that correlates with poor prognosis. Therefore, in order to improve the clinical outcome for patients with HCC, development of a chemopreventive agent that can decrease or delay the incidence of recurrence is a critical issue for urgent investigation. Acyclic retinoid (ACR, a synthetic retinoid, successfully improves HCC patient survival by preventing recurrence and the formation of secondary tumors. A malfunction of the retinoid X receptor-α (RXRα due to phosphorylation by the Ras-MAPK signaling pathway plays a critical role in liver carcinogenesis, and ACR exerts chemopreventive effects on HCC development by inhibiting RXRα phosphorylation. Here, we review the relationship between retinoid signaling abnormalities and liver disease, the mechanisms of how RXRα phosphorylation contributes to liver carcinogenesis, and the detailed effects of ACR on preventing HCC development, especially based on the results of our basic and clinical research. We also outline the concept of "clonal deletion and inhibition" therapy, which is defined as the removal and inhibition of latent malignant clones from the liver before they expand into clinically detectable HCC, because ACR prevents the development of HCC by implementing this concept. Looking toward the future, we discuss "combination chemoprevention" using ACR as a key drug since it can generate a synergistic effect, and may thus be an effective new strategy for the prevention of HCC.

  11. 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. PMID:19439309

  12. Chemopreventive and renal protective effects for docosahexaenoic acid (DHA: implications of CRP and lipid peroxides

    Directory of Open Access Journals (Sweden)

    Darweish MM

    2009-04-01

    Full Text Available Abstract Background The fish oil-derived ω-3 fatty acids, like docosahexanoic (DHA, claim a plethora of health benefits. We currently evaluated the antitumor effects of DHA, alone or in combination with cisplatin (CP in the EAC solid tumor mice model, and monitored concomitant changes in serum levels of C-reactive protein (CRP, lipid peroxidation (measured as malondialdehyde; MDA and leukocytic count (LC. Further, we verified the capacity of DHA to ameliorate the lethal, CP-induced nephrotoxicity in rats and the molecular mechanisms involved therein. Results EAC-bearing mice exhibited markedly elevated LC (2-fold, CRP (11-fold and MDA levels (2.7-fold. DHA (125, 250 mg/kg elicited significant, dose-dependent reductions in tumor size (38%, 79%; respectively, as well as in LC, CRP and MDA levels. These effects for CP were appreciably lower than those of DHA (250 mg/kg. Interestingly, DHA (125 mg/kg markedly enhanced the chemopreventive effects of CP and boosted its ability to reduce serum CRP and MDA levels. Correlation studies revealed a high degree of positive association between tumor growth and each of CRP (r = 0.85 and leukocytosis (r = 0.89, thus attesting to a diagnostic/prognostic role for CRP. On the other hand, a single CP dose (10 mg/kg induced nephrotoxicity in rats that was evidenced by proteinuria, deterioration of glomerular filtration rate (GFR, -4-fold, a rise in serum creatinine/urea levels (2–5-fold after 4 days, and globally-induced animal fatalities after 7 days. Kidney-homogenates from CP-treated rats displayed significantly elevated MDA- and TNF-α-, but reduced GSH-, levels. Rats treated with DHA (250 mg/kg, but not 125 mg/kg survived the lethal effects of CP, and showed a significant recovery of GFR; while their homogenates had markedly-reduced MDA- and TNF-α-, but -increased GSH-levels. Significant association was detected between creatinine level and those of MDA (r = 0.81, TNF-α r = 0.92 and GSH (r = -0

  13. Mechanisms of butylated hydroxytoluene chemoprevention of aflatoxicosis-inhibition of aflatoxin B1 metabolism

    International Nuclear Information System (INIS)

    Chemoprevention of toxicoses and/or cancer through the use of nutrients or pharmacologic compounds is the subject of intense study. Among the many compounds examined, food additives such as antioxidants are being considered due to their ability to reduce disease formation by either induction or inhibition of key enzyme systems. One such compound, butylated hydroxytoluene (BHT), has been found to protect against cancer formation caused by exposure to aflatoxin B1 (AFB1) in rodents. We have shown that dietary BHT protects against clinical signs of aflatoxicosis in turkeys, a species that is very susceptible to this mycotoxin. In this study, the effect of BHT on AFB1 metabolism and other cytochrome P450 (CYP)-related enzyme activities in turkey liver microsomes was examined to discern possible mechanisms of BHT-mediated protection against aflatoxicosis. Ethoxyresorufin O-deethylase (EROD), methoxyresorufin O-demethylase (MROD), prototype activities for CYP1A1 and 1A2, respectively, were decreased in the BHT fed (4000 ppm) animals, while oxidation of nifedipine, a prototype activity for CYP3A4, was increased. However, BHT added to microsomal incubations inhibited these CYP activities in a concentration-related manner. Importantly, BHT inhibited conversion of AFB1 to the reactive intermediate AFB1-8,-9-epoxide (AFBO), exhibiting Michaelis-Menton competitive inhibition kinetics (Ki = 0.81 μM). Likewise, microsomes prepared from turkeys fed BHT were significantly less active in AFBO formation compared to those from control birds. When turkeys were fed BHT for up to 40 days, residual BHT was present in liver, breast meat, thigh meat and abdominal fat in concentrations substantially below U.S. FDA guidelines for this antioxidant, but in concentrations greater than the Ki, likely sufficient to inhibit bioactivation of AFB1in vivo. BHT-induced hydropic degeneration in the livers of BHT fed animals was significantly greater in birds that remained on BHT treatment for up to 30

  14. Chemoprevention or mastectomy for women at high risk of developing breast cancer.

    Science.gov (United States)

    Sismondi, Piero; D'Alonzo, Marta; Pecchio, Silvia; Bounous, Valentina Elisabetta; Robba, Elisabetta; Biglia, Nicoletta

    2015-11-01

    Breast cancer (BC) is the most commonly diagnosed invasive cancer among women; in developed countries, BC occurs in one out of eight women during her lifetime. Many factors, both genetic and non-genetic, determine a woman's risk of breast cancer and several mathematical models have been proposed that determine the risk. It is important to identify those at high risk, as there are now effective preventive strategies, such as chemoprevention therapy and risk-reduction surgery. Risk-reduction agents are recommended for women aged 35 years or more who are at high risk of breast cancer. Tamoxifen is presently deemed to be the agent of choice. However, raloxifene may be preferable, at least for some postmenopausal women, because of its lack of effect on the endometrium and the reduced incidence of venous thromboembolic events compared with tamoxifen. Prophylactic surgery has been widely investigated. Bilateral mastectomy decreases the risk of developing breast cancer by approximately 90% in women at moderate or high risk and in known BRCA1/2 mutation carriers. This review summarizes the recent advances in the identification of women at high risk of developing breast cancer and reports on the strategies used to prevent breast cancer; the risk-benefit balance of such preventive choices is also briefly analyzed. PMID:26276104

  15. Chemopreventive properties of indole-3-carbinol, diindolylmethane and other constituents of cardamom against carcinogenesis.

    Science.gov (United States)

    Acharya, Asha; Das, Ila; Singh, Sushmita; Saha, Tapas

    2010-06-01

    Oxidative stress results from an imbalance in the production of reactive oxygen species (ROS) and cell's own antioxidant defenses that in part lead to numerous carcinogenesis. Several phytochemicals, derived from vegetables, fruits, herbs and spices, have demonstrated excellent chemopreventive properties against carcinogenesis by regulating the redox status of the cells during oxidative stress. I3C (indole-3-carbinol) and DIM (diindolylmethane) are the phytochemicals that are found in all types of cruciferous vegetables and demonstrated exceptional anti-cancer effects against hormone responsive cancers like breast, prostate and ovarian cancers. Novel analogs of I3C were designed to enhance the overall efficacy, particularly with respect to the therapeutic activity and oral bioavailability and that results in several patent applications on symptoms associated with endometriosis, vaginal neoplasia, cervical dysplasia and mastalgia. Likewise, DIM and its derivatives are patented for treatment and prevention of leiomyomas, HPV infection, respiratory syncytial virus, angiogenesis, atherosclerosis and anti-proliferative actions. On the other hand, phytochemicals in cardamom have not been explored in great details but limonene and cineole demonstrate promising effects against carcinogenesis. Thus studies with selected phytochemicals of cardamom and bioavailability research might lead to many patent applications. This review is focused on the patents generated on the effects of I3C, DIM and selected phytochemicals of cardamom on carcinogenesis. PMID:20653562

  16. Chemopreventive activity of sesquiterpene lactones (SLs) from yacon against TPA-induced Raji cells deformation.

    Science.gov (United States)

    Siriwan, D; Miyawaki, C; Miyamoto, T; Naruse, T; Okazaki, K; Tamura, H

    2011-05-15

    Yacon is a medicinal plant used as a traditional medicine by the natives in South America. In Japan, it becomes popular as a health food. Sesquiterpene Lactones (SLs) from yacon leaves were investigated and the active SLs such as enhydrin, uvedalin and sonchifolin, bearing alpha-methylene-gamma-lactone and epoxides as the active functional groups, were identified by 1H-6000 MHz-NMR. Chemopreventive and cytotoxic activities were determined using different primary screening methods. In this study, all tested SLs strongly inhibited TPA-induced deformed of Raji cells. The IC50 values of yacon SLs from anti-deforming assay were 0.04-0.4 microM. Interestingly, yacon SLs showed more potential of chemo preventive activity than both curcumin and parthenolide. However, the cytotoxicity on Raji cells was observed at high concentration of yacon SLs. The degree of anti-deformation was ranked in order: enhydrin >uvedalin >sonchifolin >parthenolide >curcumin. As according to structure-activity relationship, the high activities of enhydrin, uvedalin and sonchifolin may be due to the 2-methyl-2-butenoate and its epoxide moiety. PMID:22097098

  17. The chemopreventive flavonoid apigenin confers radiosensitizing effect in human tumor cells grown as monolayers and spheroids

    International Nuclear Information System (INIS)

    Apigenin, a common dietary flavonoid present in many fruits and vegetables, is a nonmutagenic chemopreventive agent. In the present study, we investigated the effect of apigenin on the radiosensitivity of SQ-5 cells, which are derived from a human lung carcinoma. Actively growing cells were incubated for 16 h at 37 deg C in medium containing 40 μM apigenin. The cells were then irradiated with X-rays and incubated with apigenin for a further 8 h. Radiosensitivity was assessed using a clonogenic assay. Apoptosis and necrosis were assessed using acridine orange/ethidium bromide double staining. Cells incubated with apigenin exhibited significantly greater radiosensitivity and apoptosis levels than cells not incubated with apigenin. Protein levels were measured by Western blotting. Incubation with apigenin increased protein expression of WAF1/p21 and decreased protein expression of Bcl-2. Furthermore, apigenin sensitized SQ-5 spheroids (cell aggregates growing in a three-dimensional structure that simulate the growth and microenvironmental conditions of in vivo tumors) to radiation. Thus, apigenin appears to be a promising radiosensitizing agent for use against human carcinomas. (author)

  18. Oriental herbs as a source of novel anti-androgen and prostate cancer chemopreventive agents

    Institute of Scientific and Technical Information of China (English)

    Junxuan L(U); Sung-Hoon KIM; Cheng JIANG; HyoJeong LEE; Junming GUO

    2007-01-01

    Androgen and androgen receptor (AR) signaling are crucial for the genesis of prostate cancer (Pca), which can often develop into androgen-ligand-indepen-dent diseases that are lethal to the patients. Recent studies show that even these hormone-refractory Pca require ligand-independent AR signaling for survival. As current chemotherapy is largely ineffective for Pca and has serious toxic side-effects, we have initiated a collaborative effort to identify and develop novel, safe and naturally occurring agents that target AR signaling from Oriental medicinal herbs for the chemoprevention and treatment of Pca. We highlight our discovery of decursin from an Oriental formula containing Korean Angelica gigas Nakal(Dang Gui) root as a novel anti-androgen/AR agent. We have identified the following mechanisms to account for the specific anti-AR actions: rapid block of AR nuclear translocation, inhibition of binding of 5α-dihydrotestesterone to Arand increased proteasomal degradation of AR protein. Furthermore, decursin lacks the agonist activity of the "pure" anti-androgen bicalutamide and is more potent than bicalutamide in inducing Pca apoptosis. Structure-activity analyses reveal a critical requirement of the side-chain on decursin or its structural isomerdecursinol angelate for anti-AR, cell cycle arrest and proapoptotic activities. This work demonstrates the feasibility of using activity-guided fractionation in cell culture assays combined with mechanistic studies to identify novel anti-andro-gen/AR agents from complex herbal mixtures.

  19. 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.

  20. Nitroxides as antioxidants – possibilities of their application in chemoprevention and radioprotection

    Directory of Open Access Journals (Sweden)

    Sabina Tabaczar

    2011-01-01

    Full Text Available Nitroxides as stabile organic radicals were used initially as spin labels in spectroscopy of electron paramagnetic resonance (EPR with respect to parameters such as pH of an intercellular environment, oxygenation of cells and tissues, fluidity of biological membranes, conformational state and topography of proteins. Nitroxides have also been used in biology and medicine as contrast agents in magnetic resonance imaging (MRI. When their antioxidant activities were discovered, an era of research on the potential utility of these agents began. Nitroxides can modulate the redox state of the cell by participation in oxidation/reduction reactions. Therefore, they are extensively examined in various models of oxidative stress. The antioxidant effect of nitroxides is a result of their ability to catalyze dismutation of superoxide radical (superoxide dismutase-like activity, inhibit lipid peroxidation, prevent Fenton and Haber-Weiss reactions by oxidation of transition metal ions to a higher oxidative state, and confer catalase-like activity on heme proteins. In the present paper the antioxidative mechanisms of nitroxides are presented. The relation between structure, function and the rate of nitroxide reduction inside cells and tissues is also presented. The application of nitroxides in chemoprevention and radioprotection is discussed.

  1. Salvianolic Acid B, a Potential Chemopreventive Agent, for Head and Neck Squamous Cell Cancer

    Directory of Open Access Journals (Sweden)

    Yuan Zhao

    2011-01-01

    Full Text Available Head and neck squamous cell cancer (HNSCC is one of the top ten cancers in the United States. The survival rate of HNSCC has only marginally improved over the last two decades. In addition, African-American men bear a disproportionate burden of this preventable disease. Therefore, a critical challenge of preventive health approaches is warranted. Salvianolic acid B (Sal-B isolated from Salvia miltiorrhiza Bge, which is a well-know Chinese medicines has been safely used to treat and prevent aging diseases for thousand of years. Recently, the anticancer properties of Sal-B have received more attention. Sal-B significantly inhibits or delays the growth of HNSCC in both cultured HNSCC cells and HNSCC xenograft animal models. The following anticancer mechanisms have been proposed: the inhibition of COX-2/PGE-2 pathway, the promotion of apoptosis, and the modulation of angiogenesis. In conclusion, Sal-B is a potential HNSCC chemopreventive agent working through antioxidation and anti-inflammation mechanisms.

  2. A review of the content of the putative chemopreventive phytoalexin resveratrol in red wine

    DEFF Research Database (Denmark)

    Stervbo, Ulrik; Vang, Ole; Bonnesen, Christine

    2007-01-01

    Resveratrol, a naturally occurring compound of various fruits such as grapes, is thought to possess chemopreventive properties. The levels of resveratrol in grapes and grape products including wine, varies from region to region and from one year to another. This paper reviews the resveratrol...... content in red wine based on relevant published data. Red wine contains an average of 1.9 ± 1.7 mg trans-resveratrol/ l (8.2 ± 7.5 lM), ranging from non-detectable levels to 14.3 mg/l (62.7 lM) trans-resveratrol. In general, wines made from grapes of the Pinot Noir and St. Laurent varieties showed the...... highest level of trans-resveratrol. No region can be said to produce wines with significantly higher level of trans-resveratrol than all other regions. Levels of cis-resveratrol follow the same trend as trans-resveratrol. The average level of trans-resveratrol-glucoside (trans-piceid) in a red wine may be...

  3. Chemopreventive Effects of RXR-Selective Rexinoid Bexarotene on Intestinal Neoplasia of ApcMin/+ Mice

    Directory of Open Access Journals (Sweden)

    Naveena B. Janakiram

    2012-02-01

    Full Text Available Retinoid X receptor (RXR has been implicated in several neoplastic diseases. Previously, we have shown that RXR-α is downregulated in human and rodent colonic tumors, suggesting a potential target for colon cancer prevention (http://www.cancer.org/Cancer/ColonandRectumCancer/DetailedGuide/colorectal-cancer-key-statistics. Experiments were designed to assess the chemopreventive efficacy of the selective RXR agonist bexarotene for the suppression of intestinal tumorigenesis in ApcMin/+ mice. Before the efficacy studies, we determined that the maximal tolerated dose in C57BL/6J mice was less than 400 ppm. For the efficacy study, 6-week-old male and female C57BL/6J-ApcMin/+ mice (nine mice per group were fed diets containing 0, 30, and 60 ppm of bexarotene or 200 ppm of bexarotene for 80 days before intestinal tumors were evaluated. Dietary administration of 30 and 60 ppm of bexarotene suppressed the intestinal polyp formation by 38% (P < .015 and 60% (P < .0001 in males, respectively, and by 8.5% and 37% (P < .007 in females, respectively. Also, significant inhibition (50%–100% of colonic tumor formation was observed in both male and female mice with bexarotene treatment. Administration of 200 ppm of bexarotene showed significant suppression of tumor formation (66%, P < .0001; however, it had significant toxicity. Intestinal tumors of bexarotene-fed mice showed significantly reduced expression of proliferating cell nuclear antigen (60%, P < .0001, cyclin D1, and cyclooxygenase 2 and increased RXR-α messenger RNA and uptake of oleate (34%, P < .01. Also, bexarotene-fed mice showed dose-dependent suppression of serum triglycerides (25%–72%, P < .0001 and inflammatory cytokines.

  4. 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.

  5. Colon cancer chemopreventive efficacy of silibinin through perturbation of xenobiotic metabolizing enzymes in experimental rats.

    Science.gov (United States)

    Sangeetha, Nagarajan; Viswanathan, Periyaswamy; Balasubramanian, Thangavel; Nalini, Namasivayam

    2012-01-15

    Our findings reported so far demonstrate that silibinin modulates gut microbial enzymes, colonic oxidative stress and Wnt/β-catenin signaling, to exert its antiproliferative effect against 1,2 di-methylhydrazine (DMH) induced colon carcinogenesis. Since xenobiotic metabolizing enzymes play a crucial role in carcinogen activation and metabolism, we aimed to explore the effect of silibinin on xenobiotic metabolizing enzymes during DMH induced colon carcinogenesis. Male albino rats were randomly divided into six groups. Group 1 served as control and group 2 rats received 50mg/kg body weight of silibinin p.o. every day. Groups 3-6 rats were given DMH at a dose of (20mg/kg body weight subcutaneously) once a week for 15 weeks to induce colonic tumors. In addition to DMH, group 4 (initiation), group 5 (post-initiation) and group 6 (entire period) rats received silibinin (50mg/kg body weight, p.o., everyday) at different time points during the experimental period of 32 weeks. Rats exposed to DMH alone showed increased activities of phase I enzymes (cytochrome b5, cytochrome b5 reductase, cytochromeP450, cytochromeP450 reductase, cytochromP4502E1) and decreased activities of phase II enzymes (Uridine diphospho glucuronyl transferase, Glutathione-S-transferase and DT-Diaphorase) in the liver and colonic mucosa as compared to control rats. Silibinin supplementation modulates the xenobiotic metabolizing enzymes favoring carcinogen detoxification. Evaluation of lipid peroxidation and antioxidants status showed that silibinin supplementation counteracts DMH induced hepatic and circulatory oxidative stress. Tumor burden in experimental animals was assessed both macroscopically and microscopically in the colon tissues. Our findings emphasize the potential chemopreventive action of silibinin against DMH induced colon carcinogenesis. PMID:22115893

  6. Folic acid supplementation inhibits recurrence of colorectal adenomas: A randomized chemoprevention trial

    Institute of Scientific and Technical Information of China (English)

    Richard Jaszewski; Adhip PN Majumdar; Sabeena Misra; Martin Tobi; Nadeem Ullah; Jo Ann Naumoff; Omer Kucuk; Edi Levi; Bradley N Axelrod; Bhaumik B Patel

    2008-01-01

    AIM: To determine whether folic acid supplementation will reduce the recurrence of colorectal adenomas,the precursors of colorectal cancer, we performed a double-blind placebo-controlled trial in patients with adenomatous polyps.METHODS: In the current double-blind, placebo-controlled trial at this VA Medical Center, patients with colorectal adenomas were randomly assigned to receive either a daily 5 mg dose of folic acid or a matched identical placebo for 3 years. All polyps were removed at baseline colonoscopy and each patient had a follow up colonoscopy at 3 years. The primary endpoint was a reduction in the number of recurrent adenomas at 3 years.RESULTS: Of 137 subjects, who were eligible after confirmation of polyp histology and run-in period to conform compliance, 94 completed the study; 49 in folic acid group and 45 in placebo group. Recurrence of adenomas at 3-year was compared between the two groups. The mean number of recurrent polyps at 3-year was 0.36 (SD, 0.69) for folic acid treated patients compared to 0.82 (SD, 1.17) for placebo treated subjects, resulting in a 3-fold increase in polyp recurrence in the placebo group. Patients below 70 years of age and those with left-sided colonic adenomas or advanced adenomas responded better to folic acid supplementation.CONCLUSION: High dose folic acid supplementation is associated with a significant reduction in the recurrence of colonic adenomas suggesting that folic acid may be an effective chemopreventive agent for colorectal neoplasia.

  7. CANCER CHEMOPREVENTIVE ACTIVITIES OF S-3-1,A SYNTHETIC DERIVATIVE OF DANSHINONE

    Institute of Scientific and Technical Information of China (English)

    XIAO-GUANG CHEN; YAN LI; CHUN-HONG YAN; LIAN-NIANG LI; RUI HAN

    2001-01-01

    Salvia miltiorrhiza is a traditional Chinese medicine which has been well documented for its anti-cancer effects. Based on the structure of danshinone, one of the active compounds derived from Salvia miltiorrhiza, we synthesized a simplified phenolic analog, S-3-1, and tried to explore its possible actions in preventing the development of cancer. With the Ames test, S-3-1 was found to efficiently suppress the mutagenicity of benzo[a]pyrene. This result is consistent with the inhibitory effect of S-3-1 on the activation of benzo[α]pyrene by hepatic microsomal enzymes. Besides the anti-initiation effects, S-3-1 could significantly inhibit the croton oil induced increase of mouse skin epithermal ornithine decarboxylase activity. Moreover, S-3-1 quenched both superoxide and hydroxyl free radicals whereas it inhibited lipid peroxidation in the in vitro model. These results suggest that S-3-1 might act as anti-initiation and anti-promo tion agents through reversing the biochemical alterations induced by carcinogen during carcino genesis. Therefore, we further investigated the effects of S-3-1 on carcinogenesis. In vitro, S-3-1inhibited the benzo[a]pyrene-induced transformation of V79 Chinese hamster lung fibroblasts.At 10-40 mg/kg, S-3-1 was found to inhibit the development of DM BA/croton oil-induced skin papilloma in mice through decreasing the incidence of papilloma, prolonging the latent period of tumor occurrence and reducing tumor number per mouse in a dose-dependent manner. We concluded from this study that S-3-1 might be developed as a new chemopreventive drug.

  8. Chemoprevention of HBV-related hepatocellular carcinoma by the combined product of resveratrol and silymarin in transgenic mice

    Directory of Open Access Journals (Sweden)

    Wen-Chuan Hsieh

    2013-09-01

    Full Text Available ABSTRACTBackground: Patients with chronic hepatitis B virus (HBV infection are at a high risk to develop hepatocellular carcinoma (HCC. Recently, metabolic syndrome has been found to carry a risk for HCC development. Considering the limitation of chemotherapeutic drugs for HCCs, the development of chemopreventive agents for high risk chronic HBV carriers is urgently demanded. In this study, we used combined silymarin and resveratrol extract which have been shown to exhibit biologic effects on activating peroxisome proliferator activated receptors (PPAR and inhibiting mTOR signaling in a transgenic mice model harboring HBV viral oncoproteins.Methods: The transgenic mice model harboring HBx and pre-S2 mutant constructs which develop HCC was adopted. First, we in vitro tested the ideal combination dosages of the silymarin and resveratrol product, and then we fed the natural product to the transgenic mice.The chemopreventive effects on preventing the development of HCC were evaluated.Results: MTT assay showed an enhanced effect of the combined silymarin and resveratrol product on the reduction of cell proliferation in two hepatoma cell lines, Huh-7 and Hep G2. In vitro reporter assay and Western blot analyses revealed that the combined product couldactivate PPAR/PGC-1 signaling and inhibit mTOR expression. In vivo, the combined products could significantly ameliorate fatty liver and reduce HCCs in transgenic miceharboring HBV oncoproteins.Conclusions: The combined silymarin and resveratrol product exhibits a synergistic effect on the reduction of HCC development in transgenic mice model and may represent a potential agent for the prevention of HCC in high risk chronic HBV carriers.Key words: HBV, HCC, Transgenic mice, Chemoprevention

  9. Synergistic chemopreventive effects of curcumin and berberine on human breast cancer cells through induction of apoptosis and autophagic cell death.

    Science.gov (United States)

    Wang, Kai; Zhang, Chao; Bao, Jiaolin; Jia, Xuejing; Liang, Yeer; Wang, Xiaotong; Chen, Meiwan; Su, Huanxing; Li, Peng; Wan, Jian-Bo; He, Chengwei

    2016-01-01

    Curcumin (CUR) and berberine (BBR) are renowned natural compounds that exhibit potent anticancer activities through distinct molecular mechanisms. However, the anticancer capacity of either CUR or BBR is limited. This prompted us to investigate the chemopreventive potential of co-treatment of CUR and BBR against breast cancers. The results showed that CUR and BBR in combination synergistically inhibited the growth of both MCF-7 and MDA-MB-231 breast cancer cells than the compounds used alone. Further study confirmed that synergistic anti-breast cancer activities of co-treatment of these two compounds was through inducing more apoptosis and autophagic cell death (ACD). The co-treatment-induced apoptosis was caspase-dependent and through activating ERK pathways. Our data also demonstrated that co-treatment of CUR and BBR strongly up-regulated phosphorylation of JNK and Beclin1, and decreased phosphorylated Bcl-2. Inhibition of JNK by SP600125 markedly decreased LC3-II and Beclin1, restored phosphorylated Bcl-2, and reduced the cytotoxicity induced by the two compounds in combination. These results strongly suggested that JNK/Bcl-2/Beclin1 pathway played a key role in the induction of ACD in breast cancer cells by co-treatment of CUR and BBR. This study provides an insight into the potential application of curcumin and berberine in combination for the chemoprevention and treatment of breast cancers. PMID:27263652

  10. Cancer chemoprevention: Evidence of a nonlinear dose response for the protective effects of resveratrol in humans and mice.

    Science.gov (United States)

    Cai, Hong; Scott, Edwina; Kholghi, Abeer; Andreadi, Catherine; Rufini, Alessandro; Karmokar, Ankur; Britton, Robert G; Horner-Glister, Emma; Greaves, Peter; Jawad, Dhafer; James, Mark; Howells, Lynne; Ognibene, Ted; Malfatti, Michael; Goldring, Christopher; Kitteringham, Neil; Walsh, Joanne; Viskaduraki, Maria; West, Kevin; Miller, Andrew; Hemingway, David; Steward, William P; Gescher, Andreas J; Brown, Karen

    2015-07-29

    Resveratrol is widely promoted as a potential cancer chemopreventive agent, but a lack of information on the optimal dose prohibits rationally designed trials to assess efficacy. To challenge the assumption that "more is better," we compared the pharmacokinetics and activity of a dietary dose with an intake 200 times higher. The dose-response relationship for concentrations generated and the metabolite profile of [(14)C]-resveratrol in colorectal tissue of cancer patients helped us to define clinically achievable levels. In Apc(Min) mice (a model of colorectal carcinogenesis) that received a high-fat diet, the low resveratrol dose suppressed intestinal adenoma development more potently than did the higher dose. Efficacy correlated with activation of adenosine monophosphate-activated protein kinase (AMPK) and increased expression of the senescence marker p21. Nonlinear dose responses were observed for AMPK and mechanistic target of rapamycin (mTOR) signaling in mouse adenoma cells, culminating in autophagy and senescence. In human colorectal tissues exposed to low dietary concentrations of resveratrol ex vivo, we measured enhanced AMPK phosphorylation and autophagy. The expression of the cytoprotective NAD(P)H dehydrogenase, quinone 1 (NQO1) enzyme was also increased in tissues from cancer patients participating in our [(14)C]-resveratrol trial. These findings warrant a revision of developmental strategies for diet-derived agents designed to achieve cancer chemoprevention. PMID:26223300

  11. In Vivo Immunomodulation and Lipid Peroxidation Activities Contributed to Chemoprevention Effects of Fermented Mung Bean against Breast Cancer

    Directory of Open Access Journals (Sweden)

    Swee Keong Yeap

    2013-01-01

    Full Text Available Mung bean has been reported to have antioxidant, cytotoxic, and immunomodulatory effects in vitro. Fermented products are reported to have enhanced immunomodulation and cancer chemopreventive effects. In this study, fermented mung bean treatments in vivo were studied by monitoring tumor development, spleen immunity, serum cytokine (interleukin 2 and interferon gamma levels, and spleen/tumor antioxidant levels after injection with low and high risk 4T1 breast cancer cells. Pretreatment with fermented mung bean was associated with delayed tumor formation in low risk mice. Furthermore, this treatment was connected with higher serum anticancer cytokine levels, spleen T cell populations, splenocyte cytotoxicity, and spleen/tumor antioxidant levels. Histopathological evaluation of fermented mung bean treated tumor revealed lower event of mitotic division. On the other hand, antioxidant and nitric oxide levels that were significantly increased in the untreated mice were inhibited in the fermented mung bean treated groups. These results suggested that fermented mung bean has potential cancer chemoprevention effects through the stimulation of immunity, lipid peroxidation, and anti-inflammation.

  12. In vivo phase II-enzymes inducers, as potential chemopreventive agents, based on the chalcone and furoxan skeletons.

    Science.gov (United States)

    Cabrera, Mauricio; Mastandrea, Ignacio; Otero, Gabriel; Cerecetto, Hugo; González, Mercedes

    2016-04-15

    Cancer chemoprevention involves prevention/delay/reverse of the carcinogenic process through administration of cancer chemopreventive agents (CCA). Compounds which are able to induce detoxification-enzymes, especially monofunctional phase II enzymes, have become in excellent approaches for new CCA. Herein, we report the synthesis of new furoxanyl chalcone-like hybrid compounds as CCA. In vitro studies showed that phenylfuroxanyl derivatives 6 and 9 displayed the best activities being 9 the greatest monofunctional-inducer. Additionally, compounds were non-mutagenic against TA98 Salmonella typhimurium strain (Ames test) and could be used in the prevention of the progression of pre-malignant lesions for their cytotoxic activity against tumoral cells. In vivo proof of concept showed increment on phase II-enzymes activities in liver, colon and mammary gland having derivative 9 the best induction profiles. We probed Nrf2 nuclear translocation is operative for both compounds allowing to exert protective effects via expression of downstream phase-II enzymes. PMID:26970663

  13. A theoretical study on predicted protein targets of apple polyphenols and possible mechanisms of chemoprevention in colorectal cancer.

    Science.gov (United States)

    Scafuri, Bernardina; Marabotti, Anna; Carbone, Virginia; Minasi, Paola; Dotolo, Serena; Facchiano, Angelo

    2016-01-01

    We investigated the potential role of apple phenolic compounds in human pathologies by integrating chemical characterization of phenolic compounds in three apple varieties, computational approaches to identify potential protein targets of the compounds, bioinformatics analyses on data from public archive of gene expression data, and functional analyses to hypothesize the effects of the selected compounds in molecular pathways. Starting by the analytic characterization of phenolic compounds in three apple varieties, i.e. Annurca, Red Delicious, and Golden Delicious, we used computational approaches to verify by reverse docking the potential protein targets of the identified compounds. Direct docking validation of the potential protein-ligand interactions has generated a short list of human proteins potentially bound by the apple phenolic compounds. By considering the known chemo-preventive role of apple antioxidants' extracts against some human pathologies, we performed a functional analysis by comparison with experimental gene expression data and interaction networks, obtained from public repositories. The results suggest the hypothesis that chemo-preventive effects of apple extracts in human pathologies, in particular for colorectal cancer, may be the interference with the activity of nucleotide metabolism and methylation enzymes, similarly to some classes of anticancer drugs. PMID:27587238

  14. Chemopreventive Action of Bacopa monnieri (Brahmi Hydromethanolic Extract on DMBA- Induced Skin Carcinogenesis in Swiss Albino Mice

    Directory of Open Access Journals (Sweden)

    Shiki Vishnoi

    2013-07-01

    Full Text Available Bacopa monnieri (L. Wettst. (Brahmi (Family: Scrophulariaceae, has been used in the Ayurvedic system of medicine for centuries. In the present study, Cancer Chemopreventive property of B. monnieri was evaluated on 7,12-dimethyl benz(aanthracene (DMBA induced skin papillomagenesis in male Swiss albino mice (6-7 weeks old. A single topical application of 7,12-dimethyl benz(aanthracene (104 µg/100 µl of acetone, followed 2 weeks later by repeated application of croton oil (1% in 100 µl acetone two times in a week and continued till the end of the experiment (After 16 weeks exhibited 100% tumor incidence. In contrast, mice topically treated on the shaven dorsal side with the Bacopa monnieri Hydromethanolic extract (BMH (dose 120 mg/kg body wt. & (dose 240mg/kg body wt. at one hour before each application of 1% Croton oil two times in a week., a significant reduction in the values of tumor incidence, average number of tumors per tumor bearing mouse and papillomas per papilloma bearing mouse were observed. Thus results showed that BMH possesses a Chemopreventive activity and provide evidences for its traditional usage in clinical studies.

  15. Chemoprevention by Triticum Aestivum of mouse skin carcinogenesis induced by DMBA and croton oil - association with oxidative status.

    Science.gov (United States)

    Arya, Priyanka; Kumar, Madhu

    2011-01-01

    Chemopreventive action of wheat grass (Triticum astivum) leaf extract in Swiss albino mice was evaluated. Oral administration of wheat grass leaf extract at a dose level of 20 ml/kg body weight per day at pre, peri, and post-initional phases and in combination group, caused significant variation in tumour incidence and tumour yield as compared to the control group. Moreover, the average latent period was significantly increased from 9.87 ± 0.12 to 13.4 ± 0.23 weeks in the combination group, together with significant elevation of reduced glutathione (GSH), superoxide dismutase (SOD) catalase (CAT) and reduction in lipid peroxidation (LPO) was observed as compared to the control group. PMID:21517247

  16. Chemopreventive potential of Tribulus terrestris against 7,12- dimethylbenz (a) anthracene induced skin papillomagenesis in mice.

    Science.gov (United States)

    Kumar, Manish; Soni, Anil Kumar; Shukla, Shalini; Kumar, Ashok

    2006-01-01

    In the present investigation, the chemopreventive potential of aqueous extracts of the root and fruit of Tribulus terrestris (an Ayurvedic medicinal plant) on 7, 12 - dimethylbenz (a) anthracene (DMBA) induced papillomagenesis in male Swiss albino mice was studied. A significant reduction in tumor incidence, tumor burden and cumulative number of papillomas was observed, along with a significant increase in average latent period in mice treated orally with Tribulus terrestris suspension continuously at pre, peri and post-initiation stages of papillomagenesis as compared to the control group treated with DMBA and croton oil alone. Treatment with Tribulus terrestris suspension by oral gavage for 7 days resulted in a significant increase in the reduced glutathione content in the liver (P< 0.001 for both root and fruit extracts). Conversely, lipid peroxidation levels were significantly decreased (P< 0.001). PMID:16839225

  17. Evaluation of the chemopreventive response of naringenin-loaded nanoparticles in experimental oral carcinogenesis using laser-induced autofluorescence spectroscopy

    International Nuclear Information System (INIS)

    The aim of the present study is to investigate the chemopreventive effects of prepared naringenin-loaded nanoparticles (NARNPs) relative to the efficacy of free naringenin (NAR) in modifying the carcinogenic process and to study the changes in the endogenous fluorophores during DMBA-induced hamster buccal pouch (HBP) carcinogenesis by laser-induced autofluorescence (LIAF) spectroscopy. LIAF emission spectra from the hamster buccal mucosa of the control and experimental groups of animals were recorded in the 350–700 nm spectral range on a miniature fiber optic spectrometer from different anatomical sites of each group, with excitation at 404 nm from a diode laser. Oral squamous cell carcinoma (OSCC) was developed in the buccal pouch of golden Syrian hamsters by painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. DMBA-painted animals revealed morphological changes, hyperplasia, dysplasia and well-differentiated squamous cell carcinoma. LIAF emission spectra showed significant difference between the control and tumor tissues. The tumor tissues are characterized by an increase in the emission of porphyrins and a decrease in the emission of nicotinamide adenine dinucleotide hydrogenase (NADH) and flavin adenine nucleotide (FAD) when compared to the control tissues. Furthermore, oral administration of NAR and its nanoparticulates restored the status of endogenous fluorophores in the buccal mucosa of DMBA-painted animals. On a comparative basis, the treatment of nanoparticulate naringenin was found to be more effective than free naringenin in completely preventing the formation of squamous cell carcinoma and in improving the status of endogenous porphyrins to a normal range in DMBA-induced hamster buccal pouch carcinogenesis. The result of the present study further suggests that LIAF spectroscopy may be a very valuable tool for rapid and sensitive detection of endogenous fluorophore changes in response to chemopreventive agents. (paper)

  18. Evaluation of the chemopreventive response of naringenin-loaded nanoparticles in experimental oral carcinogenesis using laser-induced autofluorescence spectroscopy

    Science.gov (United States)

    Sulfikkarali, N. K.; Krishnakumar, N.

    2013-04-01

    The aim of the present study is to investigate the chemopreventive effects of prepared naringenin-loaded nanoparticles (NARNPs) relative to the efficacy of free naringenin (NAR) in modifying the carcinogenic process and to study the changes in the endogenous fluorophores during DMBA-induced hamster buccal pouch (HBP) carcinogenesis by laser-induced autofluorescence (LIAF) spectroscopy. LIAF emission spectra from the hamster buccal mucosa of the control and experimental groups of animals were recorded in the 350-700 nm spectral range on a miniature fiber optic spectrometer from different anatomical sites of each group, with excitation at 404 nm from a diode laser. Oral squamous cell carcinoma (OSCC) was developed in the buccal pouch of golden Syrian hamsters by painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. DMBA-painted animals revealed morphological changes, hyperplasia, dysplasia and well-differentiated squamous cell carcinoma. LIAF emission spectra showed significant difference between the control and tumor tissues. The tumor tissues are characterized by an increase in the emission of porphyrins and a decrease in the emission of nicotinamide adenine dinucleotide hydrogenase (NADH) and flavin adenine nucleotide (FAD) when compared to the control tissues. Furthermore, oral administration of NAR and its nanoparticulates restored the status of endogenous fluorophores in the buccal mucosa of DMBA-painted animals. On a comparative basis, the treatment of nanoparticulate naringenin was found to be more effective than free naringenin in completely preventing the formation of squamous cell carcinoma and in improving the status of endogenous porphyrins to a normal range in DMBA-induced hamster buccal pouch carcinogenesis. The result of the present study further suggests that LIAF spectroscopy may be a very valuable tool for rapid and sensitive detection of endogenous fluorophore changes in response to chemopreventive agents.

  19. Organ-specific exposure and response to sulforaphane, a key chemopreventive ingredient in broccoli: implications for cancer prevention.

    Science.gov (United States)

    Veeranki, Omkara L; Bhattacharya, Arup; Marshall, James R; Zhang, Yuesheng

    2013-01-14

    Naturally occurring sulforaphane (SF) has been extensively studied for cancer prevention. However, little is known as to which organs may be most affected by this agent, which impedes its further development. In the present study, SF was administered to rats orally either in a single dose or once daily for 7 d. Tissue distribution of SF was measured by a HPLC-based method. Glutathione S-transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1), two well-known cytoprotective phase 2 enzymes, were measured using biochemical assays to assess tissue response to SF. SF was delivered to different organs in vastly different concentrations. Tissue uptake of SF was the greatest in the stomach, declining rapidly in the descending gastro-intestinal tract. SF was rapidly eliminated through urinary excretion, and urinary concentrations of SF equivalents were 2-4 orders of magnitude higher than those of plasma. Indeed, tissue uptake level of SF in the bladder was second only to that in the stomach. Tissue levels of SF in the colon, prostate and several other organs were very low, compared to those in the bladder and stomach. Moreover, induction levels of GST and NQO1 varied by 3- to 6-fold among the organs of SF-treated rats, though not strictly correlated with tissue exposure to SF. Thus, there is profound organ specificity in tissue exposure and response to dietary SF, suggesting that the potential chemopreventive benefit of dietary SF may differ significantly among organs. These findings may provide a basis for prioritising organs for further chemopreventive study of SF. PMID:22464629

  20. α-Santalol, a skin cancer chemopreventive agent with potential to target various pathways involved in photocarcinogenesis.

    Science.gov (United States)

    Santha, Sreevidya; Dwivedi, Chandradhar

    2013-01-01

    This study is designed to investigate the chemopreventive effect and molecular mechanisms of α-santalol on UVB-induced skin tumor development in SKH-1 hairless mouse, a widely used model for human photocarcinogenesis. A dose of UVB radiation (30 mJ cm(-2) day(-1)) that is in the range of human sunlight exposure was used for the initiation and promotion of tumor. Topical treatment of mice with α-santalol (10%, wt/vol in acetone) caused reduction in tumor incidence, multiplicity and volume. In our study, the anticarcinogenic action of α-santalol against UVB-induced photocarcinogenesis was found to be associated with inhibition of inflammation and epidermal cell proliferation, cell cycle arrest and induction of apoptosis. α-Santalol pretreatment strongly inhibited UVB-induced epidermal hyperplasia and thickness of the epidermis, expression of proliferation and inflammation markers proliferating cell nuclear antigen (PCNA), Ki-67 and cyclooxygenase 2 (Cox-2). Significant decrease in the expression of cyclins A, B1, D1 and D2 and cyclin-dependent kinases (Cdk)s Cdk1 (Cdc2), Cdk2, Cdk4 and Cdk6 and an upregulated expression of cyclin-dependent kinase (CDK) inhibitor Cip1/p21 were found in α-santalol pretreated group. Furthermore, an elevated level of cleaved caspase 3 and cleaved poly (ADP-ribose) polymerase (PARP) were observed in α-santalol-treated group. Our data suggested that α-santalol is a safer and promising skin cancer chemopreventive agent with potential to target various pathways involved in photocarcinogenesis. PMID:23480292

  1. 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

    2014-08-01

    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

  2. Urinary PGE-M levels are associated with risk of colorectal adenomas and chemopreventive response to anti-inflammatory drugs.

    Science.gov (United States)

    Bezawada, Navya; Song, Mingyang; Wu, Kana; Mehta, Raaj S; Milne, Ginger L; Ogino, Shuji; Fuchs, Charles S; Giovannucci, Edward L; Chan, Andrew T

    2014-07-01

    Prostaglandin E2 (PGE2) promotes colorectal carcinogenesis. Overall, systemic PGE2 production can be assessed by measuring its major metabolite, PGE-M, in urine. We examined the potential role of PGE-M as a biomarker for colorectal adenoma risk and chemopreventive response to anti-inflammatory drugs. We conducted a prospective case-control study nested within the Nurses' Health Study. Among women who previously provided a urine sample, we identified 420 cases diagnosed with colorectal adenoma during follow-up and matched them to 420 endoscopy-negative controls. We measured urinary PGE-M using an LC/MS assay. Compared with women in the lowest quartile of urinary PGE-M, women in the highest quartile had a multivariate OR of 1.40 (95% confidence interval (CI), 0.92-2.14) for any adenoma; 0.91 (95% CI, 0.48-1.72) for low-risk adenoma (solitary adenoma aspirin/NSAIDs per week) was associated with a significant reduction in adenoma risk (multivariate OR, 0.61; 95% CI, 0.43-0.87) in women with high baseline PGE-M (quartiles 2-4), but not low PGE-M (quartile 1).Urinary PGE-M is associated with an increased risk of high-risk adenoma. Anti-inflammatory drugs seem to reduce adenoma risk among women with high, but not low PGE-M. Urinary PGE-M may serve as a biomarker to define subsets of the population who may obtain differential chemopreventive benefit from anti-inflammatory drugs. PMID:24824037

  3. 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

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

    OpenAIRE

    Carvell eNguyen; Brandon eIsariyawongse; Changhong eYu; Michael eKattan

    2012-01-01

    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 bio...

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

    OpenAIRE

    Nguyen, Carvell T.; Isariyawongse, Brandon; Yu, Changhong; Michael W Kattan

    2012-01-01

    Introduction: 5-alpha reductase inhibitors can reduce the risk of prostate cancer (PCa) 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 9 endpoints relevant to dutasteride treatment. Using the treatment and placebo groups from the biop...

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

    OpenAIRE

    Wu Qing; Saw Constance; Kong Ah-Ng Tony

    2010-01-01

    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 cel...

  7. Chemoprevention of 7,12-dimethylbenz[a]anthracene (DMBA)-induced Hamster Cheek Pouch Carcinogenesis by a 5-Lipoxygenase Inhibitor, Garcinol

    OpenAIRE

    Chen, Xin; Zhang, Xinyan; Lu, Ye; Shim, Joong-Youn; Sang, Shengmin; Sun, Zheng; Chen, Xiaoxin

    2012-01-01

    Our previous studies have shown that aberrant arachidonic acid metabolism, especially the 5-lipoxygenase (5-Lox) pathway, is involved in oral carcinogenesis, and can be targeted for cancer prevention. In order to develop potent topical agents for oral cancer chemoprevention, five known 5-Lox inhibitors from dietary and synthetic sources, Zileuton, ABT-761, Licofelone, Curcumin and Garcinol, were evaluated in silico for their potential efficacy. Garcinol, a polyisoprenylated benzophenone from ...

  8. Chemopreventive effects of Furan-2-yl-3-pyridin-2-yl-propenone against 7,12-dimethylbenz[a]anthracene-inducible genotoxicity

    International Nuclear Information System (INIS)

    1-Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) is an anti-inflammatory agent with a propenone moiety and chemically synthesized recently. In this study, we examined the chemopreventive effect of FPP-3 on 7,12-dimethylbenz[a]anthracene (DMBA)-induced genotoxicity in MCF-7 cells. FPP-3 reduced the formation of the DMBA-DNA adduct. DMBA-induced CYP1A1 and CYP1B1 gene expression and enzyme activity were inhibited by FPP-3. It inhibited DMBA-induced aryl hydrocarbon receptor (AhR) transactivation and DMBA-inducible nuclear localization of the AhR. Induction of detoxifying phase II genes by chemopreventive agents represents a coordinated protective response against oxidative stress and neoplastic effects of carcinogens. Transcription factor NF-E2 related factor 2 (Nrf2) regulates antioxidant response element (ARE) of phase II detoxifying and antioxidant enzymes, such as glutathione S-transferase (GST) and NAD(P)H:quinone oxidoreductase (QR). FPP-3 increased the expression and enzymatic activity of GST and QR. Moreover, FPP-3 increased transcriptional activity of GST and QR. GST and QR induction and Nrf2 translocation by FPP-3 were blocked by the PKC inhibitor Goe6983, and the p38 inhibitor SB203580. These results reflected a partial role of PKCδ and p38 signaling in FPP-3-mediated GSTA and QR induction through nuclear translocation of Nrf2. Classically, chemopreventive agents either inhibit CYP metabolizing enzyme or induce phase II detoxifying enzymes. These results suggest that FPP-3 has a potent protective effect against DMBA-induced genotoxicity through modulating phase I and II enzymes and that it has potential as a chemopreventive agent

  9. Feasibility, safety and effectiveness of combining home based malaria management and seasonal malaria chemoprevention in children less than 10 years in Senegal

    DEFF Research Database (Denmark)

    Tine, Roger C K; Ndour, Cheikh T; Faye, Babacar;

    2014-01-01

    Home-based management of malaria (HMM) may improve access to diagnostic testing and treatment with artemisinin combination therapy (ACT). In the Sahel region, seasonal malaria chemoprevention (SMC) is now recommended for the prevention of malaria in children. It is likely that combinations of...... antimalarial interventions can reduce the malaria burden. This study assessed the feasibility, effectiveness and safety of combining SMC and HMM delivered by community health workers (CHWs)....

  10. Cancer chemopreventive potential of volatile oil from black cumin seeds, Nigella sativa L., in a rat multi-organ carcinogenesis bioassay

    OpenAIRE

    Salim, Elsayed I.

    2010-01-01

    Nigella sativa (N. sativa) is a herbal plant of the Ranunculaceae family that has been widely used for various medicinal and nutritional purposes. Volatile oil extracts along with its major constituents, such as thymoquinone, have recently attracted considerable attention for their antioxidant, immunoprotective and antitumor properties. The present study was conducted to assess the chemopreventive potential of crude oils in N. sativa on tumor formation using a well-established rat multi-organ...

  11. N-acetil-l-cysteine and 2-amino-2-thiiazoline N-acetyl-l-cysteinate as a possible cancer chemopreventive agents in murine models.

    Science.gov (United States)

    Simkeviciene, Vitalija; Straukas, J; Uleckiene, Saule

    2002-01-01

    The aim of this study was to investigate N-acetyl-cysteine (NAC) and its 2-amino-2-thiazoline salt (NACAT) as potential chemopreventive agents on experimentally induced lung tumours by urethane (U) in mice. Female BALB/c mice were used. U was given by intraperitoneal injections during 2 weeks (single dose - 10 mg/mouse, total - 50 mg/mouse). Mice were treated daily per os with NAC 1/10 LD50, NACAT 1/10 or 1/100 LD50 starting 2 weeks prior U administration, then during U treatment and thereafter for 2 months. The duration of experiment was 4 months. The results showed that NAC (1000 mg/kg) reduced the lung tumour incidence to 30% that of controls, P < or = 0.05. Most effective of NACAT was 100 mg/kg dose; it reduced an average of lung adenomas per mouse by 26%, P < or = 0.05, but lower dose (10 mg/kg) was less effective. In order to achieve similar chemopreventive effect (approximately 30%) on mice, it is necessary to use 0.38 mM/kg of NACAT or 6.13 mM/kg of NAC. It means that 16 times less of NACAT is required, if calculated by molar concentration. In general, NAC and NACAT have a moderate chemopreventive effect on lung tumorigenesis induced by urethane in mice. PMID:12371608

  12. Chemopreventive effect of 18β-glycyrrhetinic acid via modulation of inflammatory markers and induction of apoptosis in human hepatoma cell line (HepG2).

    Science.gov (United States)

    Hasan, Syed Kazim; Siddiqi, Aisha; Nafees, Sana; Ali, Nemat; Rashid, Summya; Ali, Rashid; Shahid, Ayaz; Sultana, Sarwat

    2016-05-01

    Hepatocellular carcinoma is one of the most common lethal diseases worldwide and there is no effective treatment till date. Natural products derived from the plants play an important role in chemoprevention and act as therapeutic antitumor agents. Licorice is a plant that has been used in food and medicine for the treatment of various diseases. 18β-Glycyrrhetinic acid (18β-GA), a pentacyclic triterpenoid obtained from the roots of licorice plant, is reported to possess various pharmacological properties such as antitumor and antiinflammatory activities. The present study was designed to elucidate the chemopreventive effect of 18β-GA through antiinflammation, antiproliferation, and induction of apoptosis in human hepatoma cell line HepG2. 18β-GA significantly inhibits the proliferation of HepG2 cell without affecting the normal liver cell line (Chang's). In the present study, 18β-GA increased the formation of reactive oxygen species, nitric oxide production, and loss of mitochondrial membrane potential, suggesting the involvement of 18β-GA in apoptosis which was also confirmed by assessing the markers involved in apoptosis like caspase-3, caspase-9, Bax:Bcl-2 ratio, and cleaved PARP. 18β-GA also downregulated the expression of inflammatory proteins such as NF-κB, iNOS, and COX-2. Keeping these data into consideration, our results suggest that 18β-GA may be used as a chemopreventive agent in liver cancer. PMID:27116616

  13. A novel role of the aryl hydrocarbon receptor (AhR in centrosome amplification - implications for chemoprevention

    Directory of Open Access Journals (Sweden)

    Chatterjee Payel

    2010-06-01

    Full Text Available Abstract Background Centrosome aberrations can cause genomic instability and correlate with malignant progression in common human malignancies such as breast and prostate cancer. Deregulation of cyclin/cyclin-dependent kinase 2 (CDK2 activity has previously been shown to be critically involved in centrosome overduplication. We therefore test here whether small molecule CDK inhibitors derived from the bis-indole indirubin can be used to suppress centrosome aberrations as a novel approach to chemoprevention of malignant progression. Results As expected, we found that the CDK inhibitor indirubin-3'-oxime (IO suppresses centrosome amplification in breast cancer cells. However, we made the unexpected discovery that indirubin-derived compounds that have been chemically modified to be inactive as kinase inhibitors such as 1-methyl-indirubin-3'-oxime (MeIO still significantly reduced centrosome amplification. All indirubins used in the present study are potent agonists of the aryl hydrocarbon receptor (AhR, which is known for its important role in the cellular metabolism of xenobiotics. To corroborate our results, we first show that the coincidence of nuclear AhR overexpression, reflecting a constitutive activation, and numerical centrosome aberrations correlates significantly with malignancy in mammary tissue specimens. Remarkably, a considerable proportion (72.7% of benign mammary tissue samples scored also positive for nuclear AhR overexpression. We furthermore provide evidence that continued expression of endogenous AhR is critical to promote centriole overduplication induced by cyclin E and that AhR and cyclin E may function in the same pathway. Overexpression of the AhR in the absence of exogenous ligands was found to rapidly disrupt centriole duplication control. Nonetheless, the AhR agonists IO and MeIO were still found to significantly reduce centriole overduplication stimulated by ectopic AhR expression. Conclusions Our results indicate that

  14. Familial adenomatous polyposis in pediatrics: natural history, emerging surveillance and management protocols, chemopreventive strategies, and areas of ongoing debate.

    Science.gov (United States)

    Septer, Seth; Lawson, Caitlin E; Anant, Shrikant; Attard, Thomas

    2016-07-01

    Familial adenomatous polyposis (FAP) is a hereditary condition with a near 100 % lifetime risk of colorectal cancer without prophylactic colectomy. Most patients with FAP have a mutation in the adenomatous polyposis coli gene on chromosome 5q22. This condition frequently presents in children with polyps developing most frequently in the second decade of life and surveillance colonoscopy is required starting at age ten. Polyps are found not only in the colon, but in the stomach and duodenum. Knowledge of the natural history of FAP is important as there are several extra-colonic sequelae which also require surveillance. In infants and toddlers, there is an increased risk of hepatoblastoma, while in teenagers and adults duodenal carcinomas, desmoid tumors, thyroid cancer and medulloblastoma are more common in FAP than in the general population. Current chemopreventive strategies include several medications and natural products, although to this point there is no consensus on the most efficacious and safe agent. Genetic counseling is an important part of the diagnostic process for FAP. Appropriate use and interpretation of genetic testing is best accomplished with genetic counselor involvement as many families also have concerns regarding future insurability or discrimination when faced with genetic testing. PMID:27056662

  15. Chemopreventive effects of pequi oil (Caryocar brasiliense Camb.) on preneoplastic lesions in a mouse model of hepatocarcinogenesis.

    Science.gov (United States)

    Palmeira, Simone M; Silva, Paula R P; Ferrão, Juliana S P; Ladd, Aliny A B L; Dagli, Maria L Z; Grisolia, Cesar K; Hernandez-Blazquez, Francisco J

    2016-07-01

    Pequi (Caryocar brasiliense Camb.), a fruit from Brazil's central region, was evaluated for its chemopreventive effects on preneoplastic liver lesions induced by the carcinogen diethylnitrosamine (DEN) in mice. BALB/c mice, 14 days of age, received an intraperitoneal injection at 10 µg/g of DEN. The mice received either of two doses of pequi oil (100 or 400 mg/kg) daily from the age of 30 days and were killed at the age of 189 days. Stereological parameters, including the volume density (Vv) and the total volume (Vtot) of the lesions (preneoplastic and adenomas), were measured and the expression of cytokeratins CK8/18 was evaluated. The total volume of lesions and adenomas was reduced by 51% in the group treated with the carcinogen and 400 mg/kg of pequi oil administered daily by an oral gavage for 25 consecutive weeks. In addition, some mice in this group did not develop lesions. Among the remaining preneoplastic lesions in this group, the number of remodelled profiles increased by 2.4-fold in the 400-mg pequi oil-treated mice relative to the 100-mg-treated mice. Our results show that pequi oil exerts a hepatoprotective effect against DEN-induced development of preneoplastic lesions and adenoma in mice and the potential for its use in the prevention of liver cancer. PMID:26287697

  16. Natural chemopreventive alternatives in oral cancer chemoprevention.

    Science.gov (United States)

    Scrobota, I; Bolfa, P; Filip, A G; Catoi, C; Alb, C; Pop, O; Tatomir, C; Baciut, G

    2016-02-01

    We studied the effect of grape seed extract Burgund Mare (BM) on oral carcinogenesis and compared it with that of curcumin (CU). Wistar rats were divided into six groups (n = 10): 4-nitro-quinoline-1-oxide (4NQO) oral carcinogenesis was induced to groups 1 - 5; groups 2 and 3 received BM and CU respectively during initiation and groups 4 and 5 BM and CU during post-initiation of carcinogenesis; group 6 represented the negative control group. Total malondialdehyde (MDA) and reduced glutathione (GSH) were assayed fluorometrically in oral tissue (gingival, jugal, palatal, lingual mucosa) and serum. Histopathological exam was performed and a dysplasia score given to each oral mucosal lesion. Ki67, cyclin D1, p63, Bcl2 and p53 were immunohistochemically evaluated. BM and CU reduced tissue MDA values elevated by 4NQO (P = 0.000). The difference between CU and BM effect was significant in the initiation (P = 0.02) but not in the post-initiation phase of carcinogenesis (P = 0.58). Tissue GSH levels decreased by 4NQO (P stress and the intensity of dysplasia. During post-initiation of carcinogenesis BM and CU exhibited similar effects. PMID:27010905

  17. Disruption of androgen and estrogen receptor activity in prostate cancer by a novel dietary diterpene carnosol: implications for chemoprevention

    Science.gov (United States)

    Johnson, Jeremy J.; Syed, Deeba N.; Suh, Yewseok; Heren, Chenelle R.; Saleem, Mohammad; Siddiqui, Imtiaz A.; Mukhtar, Hasan

    2010-01-01

    Emerging data is suggesting that estrogens, in addition to androgens, may also be contributing to the development of prostate cancer (PCa). In view of this notion agents that target estrogens, in addition to androgens, may be a novel approach for PCa chemoprevention and treatment. Thus, the identification and development of non-toxic dietary agents capable of disrupting androgen receptor (AR) in addition to estrogen receptor (ER) could be extremely useful in the management of PCa. Through molecular modeling we found carnosol, a dietary diterpene fits within the ligand binding domain of both AR and ER-α. Using a TR-FRET assay we found that carnosol interacts with both AR and ER-α and additional experiments confirmed that it functions as a receptor antagonist with no agonist effects. LNCaP, 22Rv1, and MCF7 cells treated with carnosol (20–40 µM) showed decreased protein expression of AR and ER-α. Oral administration of carnosol at 30 mg/kg five days weekly for 28 days to 22Rv1 PCa xenografted mice suppressed tumor growth by 36% (p = 0.028) and was associated with a decrease in serum PSA by 26% (p=0.0042). These properties make carnosol unique to any known anti-androgen or anti-estrogen investigated so far for the simultaneous disruption of AR and ER-α. We suggest that carnosol may be developed or chemically modified through more rigorous structure activity relationship studies for a new class of investigational agents - a dual AR/ER modulator. PMID:20736335

  18. Study to evaluate molecular mechanics behind synergistic chemo-preventive effects of curcumin and resveratrol during lung carcinogenesis.

    Directory of Open Access Journals (Sweden)

    Anshoo Malhotra

    Full Text Available BACKGROUND: The combination approach is the future of the war against cancer and the present study evaluated molecular mechanics behind the synergistic effects of curcumin and resveratrol during lung carcinogenesis. METHODS: The mice were segregated into five groups which included normal control, Benzo[a]pyrene[BP] treated, BP+curcumin treated, BP+resveratrol treated and BP+curcumin+resveratrol treated. RESULTS: The morphological analyses of tumor nodules confirmed lung carcinogenesis in mice after 22 weeks of single intra-peritoneal[i.p] injection of BP at a dose of 100 mg/Kg body weight. The BP treatment resulted in a significant increase in the protein expressions of p53 in the BP treated mice. Also, a significant increase in the protein expression of phosphorylated p53[ser15] confirmed p53 hyper-phosphorylation in BP treated mice. On the other hand, enzyme activities of caspase 3 and caspase 9 were noticed to be significantly decreased following BP treatment. Further, radiorespirometric studies showed a significant increase in the 14C-glucose turnover as well as 14C-glucose uptake in the lung slices of BP treated mice. Moreover, a significant rise in the cell proliferation was confirmed indirectly by enhanced uptake of 3H-thymidine in the lung slices of BP treated mice. Interestingly, combined treatment of curcumin and resveratrol to BP treated animals resulted in a significant decrease in p53 hyper-phosphorylation, 14C glucose uptakes/turnover and 3H-thymidine uptake in the BP treated mice. However, the enzyme activities of caspase 3 and caspase 9 showed a significant increase upon treatment with curcumin and resveratrol. CONCLUSION: The study, therefore, concludes that molecular mechanics behind chemo-preventive synergism involved modulation of p53 hyper-phosphorylation, regulation of caspases and cellular metabolism enzymes.

  19. In vitro chemo-preventive activities of hydroxytyrosol: the main phenolic compound present in extra-virgin olive oil.

    Science.gov (United States)

    Rosignoli, Patrizia; Fuccelli, Raffaela; Sepporta, Maria Vittoria; Fabiani, Roberto

    2016-01-01

    The co-incubation in the culture medium with hydroxytyrosol [3,4-dihydroxyphenyl ethanol (3,4-DHPEA)], the main phenolic compound present in extra-virgin olive oil, and H2O2 reduces the oxidative DNA damage in peripheral blood mononuclear cells (PBMC). In this study we investigate, by the comet assay, the ability of 3,4-DHPEA to inhibit the H2O2 induced DNA damage when pre-incubated with PBMC and then removed before the exposure of cells to H2O2. Low doses of 3,4-DHPEA (10-100 μM) pre-incubated for 30 min with PBMC reduced the DNA damage induced by the treatment with H2O2 200 μM for 5 min at 4 °C. Prolonging the exposure time up to 6 h completely prevented the DNA damage. Furthermore we extensively analysed, by the MTT assay, the anti-proliferative activities of 3,4-DHPEA on breast (MDA and MCF-7), prostate (LNCap and PC3) and colon (SW480 and HCT116) cancer cell lines and correlated these effects with the H2O2 accumulation. The concentration of H2O2 in the culture medium was measured by the ferrous ion oxidation-xylenol orange method. The proliferation of all the cell lines was inhibited but at different levels: the prostate cancer cells were more resistant to the growth inhibition with respect to breast and colon cancer cells. The ability of the different cell lines to remove H2O2 from the culture medium was inversely correlated with their sensitivity to the anti-proliferative effect of 3,4-DHPEA. Therefore, 3,4-DHPEA may act as a chemopreventive agent acting on both initiation and promotion/progression phases of carcinogenesis. PMID:26469183

  20. Sulforaphane, a cancer chemopreventive agent, induces pathways associated with membrane biosynthesis in response to tissue damage by aflatoxin B1

    International Nuclear Information System (INIS)

    Aflatoxin B1 (AFB1) 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 AFB1-DNA adducts in AFB1-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 AFB1 and SF caused reprogramming of a network of genes involved in signal transduction and transcription. Changes in gene regulation were observable 4 h after AFB1 administration in SF-pretreated animals and may reflect regeneration of cells in the wake of AFB1-induced hepatotoxicity. At 24 h after AFB1 administration, significant induction of genes that play roles in cellular lipid metabolism and acetyl-CoA biosynthesis was detected in SF-pretreated AFB1-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 AFB1 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 B1 (AFB1)-treated rat livers. • SF redirects biochemical networks toward lipid biosynthesis in AFB1-dosed rats. • SF enhanced gene sets that would be expected to favor cell repair and regeneration

  1. Effects of chemopreventive natural products on non-homologous end-joining DNA double-strand break repair.

    Science.gov (United States)

    Charles, Catherine; Nachtergael, Amandine; Ouedraogo, Moustapha; Belayew, Alexandra; Duez, Pierre

    2014-07-01

    Double-strand breaks (DSBs) may result from endogenous (e.g., reactive oxygen species, variable (diversity) joining, meiotic exchanges, collapsed replication forks, nucleases) or exogenous (e.g., ionizing radiation, chemotherapeutic agents, radiomimetic compounds) events. DSBs disrupt the integrity of DNA and failed or improper DSBs repair may lead to genomic instability and, eventually, mutations, cancer, or cell death. Non-homologous end-joining (NHEJ) is the major pathway used by higher eukaryotic cells to repair these lesions. Given the complexity of NHEJ and the number of proteins and cofactors involved, secondary metabolites from medicinal or food plants might interfere with the process, activating or inhibiting repair. Twelve natural products, arbutin, curcumin, indole-3-carbinol, and nine flavonoids (apigenin, baicalein, chalcone, epicatechin, genistein, myricetin, naringenin, quercetin, sakuranetin) were chosen for their postulated roles in cancer chemoprevention and/or treatment. The effects of these compounds on NHEJ were investigated with an in vitro protocol based on plasmid substrates. Plasmids were linearized by a restriction enzyme, generating cohesive ends, or by a combination of enzymes, generating incompatible ends; plasmids were then incubated with a nuclear extract prepared from normal human small-intestinal cells (FHS 74 Int), either treated with these natural products or untreated (controls). The NHEJ repair complex from nuclear extracts ligates linearized plasmids, resulting in plasmid oligomers that can be separated and quantified by on-chip microelectrophoresis. Some compounds (chalcone, epicatechin, myricetin, sakuranetin and arbutin) clearly activated NHEJ, whereas others (apigenin, baicalein and curcumin) significantly reduced the repair rate of both types of plasmid substrates. Although this in vitro protocol is only partly representative of the in vivo situation, the natural products appear to interfere with NHEJ repair and warrant

  2. 植物多酚对胃癌的化学预防%Chemoprevention of plant polyphenols in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    刘入铭; 姜晶; 马麟; 曹雪源

    2012-01-01

    胃癌的发病是多因素相互作用的过程,与宿主因素、幽门螺杆菌(Hp)感染、饮食等因素相关.植物多酚是广泛存在于植物中的一大类多酚化合物的总称,具有较强的抗氧化性,许多动物实验和临床研究表明,多酚类物质能够通过抑制Hp感染、抑制核转录因子-κB(NF-κB)表达、促进肿瘤细胞凋亡等多种途径实现对胃癌的抑制.植物多酚的应用拓宽了胃癌化学预防的途径.%Gastric cancer carcinogenesis is a multifactorial process which is related to an interaction of host factors,Helieobacter pylori (Hp) infection,dietary factors and so on.The plant polyphenols which are widely present in many plants are the general term for a large group polyphenolic compounds.They have strong antioxidant activity.Furthermore,many animal experiments and clinical studies have proved that the polyphenols could inhibit gastric cancer via inhibiting Hp infection,suppressing the expression of nuclear factor-κB (NF-κB),promoting apoptosis in cancer cells and so on.The application of plant polyphenols could broaden the approaches for chemoprevention of gastric cancer.

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

    Directory of Open Access Journals (Sweden)

    Vilmar Marques de Oliveira

    2006-12-01

    Full Text Available Quimioprevenção é definida como o uso de agentes químicos naturais ou sintéticos para reverter, suprimir ou prevenir a progressão carcinogênica para carcinoma invasor. Os fármacos que agem como agentes quimiopreventivos contra o câncer de mama são divididos em dois grupos principais: os que previnem cânceres de mama receptor de estrogênio (RE positivos, como os moduladores seletivos do receptor de estrogênio (SERM, inibidores de aromatase, agonistas de GnRH e fitoestrogênios; e os fármacos que previnem os cânceres RE-negativos, como os inibidores da ciclooxigenase-2 (COX-2, retinóides, as estatinas, os inibidores do receptor tirosina quinase, o anticorpo monoclonal contra HER-2 e os inbidores da telomerase. Resultados do estudo conduzido pelo NSABP que comparou o tamoxifeno com o raloxifeno (STAR, avaliando a eficácia na redução de risco, assim como a toxicidade desses dois SERMs em uma população similar e de alto risco para câncer de mama, demonstrou que o raloxifeno é tão efetivo quanto o tamoxifeno na redução de risco de câncer de mama invasor (p=0,83 e apresentou menor risco de eventos tromboembólicos e catarata; todavia, exibiu maior risco de carcinoma não invasor, porém sem significância estatística. Baseado nos dados promissores que revelaram diminuição de risco de câncer de mama contralateral em estudos de adjuvância, alguns inibidores de aromatase, incluindo o letrozol, anastrazol e exemestane, estão sendo incorporados em investigações para avaliar sua eficácia como agentes preventivos de alto risco em mulheres. Os inibidores de COX-2 demonstraram sua eficácia na prevenção do câncer de mama em estudos caso-controle e coorte, sendo necessários estudos aleatórios para atestar sua eficácia. O resultado positivo de alguns ensaios clínicos na prevenção do câncer de mama em populações de alto risco sugere que a quimioprevenção é uma estratégia racional e atraente.Chemoprevention is

  4. Chemopreventive potential of Triphala (a composite Indian drug) on Benzo(a)pyrene induced forestomach tumorigenesis in murine tumor model system

    International Nuclear Information System (INIS)

    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

  5. Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-kappa B activation.

    Science.gov (United States)

    Surh, Y J; Chun, K S; Cha, H H; Han, S S; Keum, Y S; Park, K K; Lee, S S

    2001-09-01

    A wide array of phenolic substances, particularly those present in edible and medicinal plants, have been reported to possess substantial anticarcinogenic and antimutagenic activities. The majority of naturally occurring phenolics retain antioxidative and anti-inflammatory properties which appear to contribute to their chemopreventive or chemoprotective activity. Cyclooxygenase-2 (COX-2) inducible and nitric oxide synthase (iNOS) are important enzymes that mediate inflammatory processes. Improper up-regulation of COX-2 and/or iNOS has been associated with pathophysiology of certain types of human cancers as well as inflammatory disorders. Since inflammation is closely linked to tumor promotion, substances with potent anti-inflammatory activities are anticipated to exert chemopreventive effects on carcinogenesis, particularly in the promotion stage. Examples are curcumin, a yellow pigment of turmeric (Curcuma longa L., Zingiberaceae), the green tea polyphenol epigallocatechin gallate (EGCG), and resveratrol from grapes (Vitis vinifera, Vitaceae) that strongly suppress tumor promotion. Recent studies have demonstrated that eukaryotic transcription factor nuclear factor-kappa B (NF-kappa B) is involved in regulation of COX-2 and iNOS expression. Several chemopreventive phytochemicals have been shown to inhibit COX-2 and iNOS expression by blocking improper NF-kappa B activation. Multiple lines of compelling evidence indicate that extracellular-regulated protein kinase and p38 mitogen-activated protein kinase are key elements of the intracellular signaling cascades responsible for NF-kappa B activation in response to a wide array of external stimuli. Curcumin, EGCG and resveratrol have been shown to suppress activation of NF-kappa B. One of the plausible mechanisms underlying inhibition of NF-kappa B activation by aforementioned phytochemicals involves repression of degradation of the inhibitory unit I kappa B alpha, which hampers subsequent nuclear translocation of

  6. Paricalcitol Enhances the Chemopreventive Efficacy of 5-Fluorouracil on an Intermediate-Term Model of Azoxymethane-Induced Colorectal Tumors in Rats.

    Science.gov (United States)

    El-Shemi, Adel Galal; Refaat, Bassem; Kensara, Osama Adnan; Mohamed, Amr Mohamed; Idris, Shakir; Ahmad, Jawwad

    2016-06-01

    Colorectal cancer is a common cancer with high mortality rate. Despite being the standard anti-colorectal cancer drug, 5-fluorouracil (5-FU) exhibits only limited therapeutic benefits. Herein, we investigated whether paricalcitol, a synthetic vitamin D analogue with potential antitumor properties, would enhance the chemopreventive efficacy of 5-FU on an intermediate-term (15 weeks) model of colorectal tumors induced by azoxymethane (AOM) in rats. After AOM injection, 5-FU was administered during the 9th and 10th weeks (12 mg/kg/day for 4 days, then 6 mg/kg every other day for another 4 doses), whereas paricalcitol (2.5 μg/kg/day; 3 days/week) was given from the 7th to the 15th week. At week 15, the animals were euthanized and their resected colons were examined macroscopically and microscopically. Quantitative RT-PCR was used to measure the transcription activities of Wnt, β-catenin, DKK-1, CDNK-1A, NF-κB, and COX-2 genes, and ELISA was used to quantify the protein levels of β-catenin, COX-2, HSP90, and VEGF. IHC was additionally used to measure β-catenin, HSP90, and inducible nitric oxide synthase (iNOS). Compared with their individual therapy, combination of 5-FU and paricalcitol showed more significant reducing effect on numbers of grown tumors and large aberrant crypts foci. Mechanistically, paricalcitol and 5-FU had cooperated together to repress the expression of procancerous Wnt, β-catenin, NF-κB, COX-2, iNOS, VEGF, and HSP-90 more, and to upregulate the expression of antitumorigenesis DKK-1 and CDNK-1A, compared with their monotherapies. Our findings suggest that combined use of paricalcitol with 5-FU exhibits an augmenting chemopreventive effect against colorectal tumors, and might potentially be useful for chemoprevention in colorectal cancer patients. Cancer Prev Res; 9(6); 491-501. ©2016 AACR. PMID:27020656

  7. Chemopreventive effect of montelukast in n-nitroso n-methyl urea induced mammary carcinogenesis in female Sprague-Dawley rats

    OpenAIRE

    Manonmani Alvin Jose; Ramakrishna Amathi; Duraiswami Sathyamurthy; Balasubramanian Nandha Kumar

    2013-01-01

    Objective: The objective of the study was to evaluate the chemopreventive effect of montelukast sodium; selective reversible cysteinyl leukotriene D 4 -receptor antagonist in N-nitroso N-methyl urea (NMU) induced mammary carcinogenesis in virgin female Sprague-Dawley rats. Materials and Methods: Thirty rats were divided into five groups (normal control, disease control, montelukast1 mg/kg, montelukast10 mg/kg, tamoxifen10 mg/kg) of six animals each.The drug was administered in two doses,1...

  8. Chemopreventive and Antilipidperoxidative Potential of Clerodendron inerme (L) Gaertn in 7,12-dimethylbenz(a)anthracene Indcued Skin Carcinogenesis in Swiss Albino Mic

    OpenAIRE

    Gopi Lilly Renju; Shanmugam Manoharan; Subramanian Balakrishnan; Namasivayam Senthil

    2007-01-01

    The present study has investigated the chemopreventive and antilipidperoxidative effects of the ethanolic extract of Clerodendron inerme leaves (CiELet) in DMBA induced skin carcinogenesis in Swiss albino mice. The skin squamous cell carcinoma was induced in the shaved back of mice, by painting with DMBA (25 μg 0.1 mL-1 acetone) twice weekly for 8 weeks. We have observed 100% tumor formation in the fifteenth week of experimental period. Elevated lipid peroxidation and decline in enzymatic and...

  9. The chemopreventive activity of the histone deacetylase inhibitor tributyrin in colon carcinogenesis involves the induction of apoptosis and reduction of DNA damage

    International Nuclear Information System (INIS)

    The chemopreventive activity of the histone deacetylase inhibitor (HDACi) tributyrin (TB), a prodrug of butyric acid (BA), was evaluated in a rat model of colon carcinogenesis. The animals were treated with TB (TB group: 200 mg/100 g of body weight, b.w.) or maltodextrin (MD isocaloric control group: 300 mg/100 g b.w.) daily for 9 consecutive weeks. In the 3rd and 4th weeks of treatment, the rats in the TB and MD groups were given DMH (40 mg/kg b.w.) twice a week. After 9 weeks, the animals were euthanized, and the distal colon was examined. Compared with the control group (MD group), TB treatment reduced the total number of aberrant crypt foci (ACF; p < 0.05) as well as the ACF with ≥ 4 crypts (p < 0.05), which are considered more aggressive, but not inhibited the formation of DMH-induced O6-methyldeoxyguanosine DNA adducts. The TB group also showed a higher apoptotic index (p < 0.05) and reduced DNA damage (p < 0.05) compared with MD group. TB acted as a HDACi, as rats treated with the prodrug of BA had higher levels of histone H3K9 acetylation compared with the MD group (p < 0.05). TB administration resulted in increased colonic tissue concentrations of BA (p < 0.05) compared with the control animals. These results suggest that TB can be considered a promising chemopreventive agent for colon carcinogenesis because it reduced the number of ACF, including those that were more aggressive. Induction of apoptosis and reduction of DNA damage are cellular mechanisms that appear to be involved in the chemopreventive activity of TB. - Highlights: • Tributyrin is a chemopreventive agent for rat colon aberrant crypt foci. • Tributyrin increased apoptosis in an experimental rat colon carcinogenesis model. • Tributyrin treatment in a rat colon carcinogenesis model decreased DNA damage. • Tributyrin treatment induced H3K9 acetylation in a rat colon carcinogenesis model

  10. Sarcophine-Diol, a Skin Cancer Chemopreventive Agent, Inhibits Proliferation and Stimulates Apoptosis in Mouse Melanoma B16F10 Cell Line

    OpenAIRE

    Hesham Fahmy; Ahmed, Safwat A.; Szymanski, Pawel T.; Bhimanna Kuppast; Sherief Khalifa

    2011-01-01

    Sarcodiol (SD) is a semi-synthetic derivative of sarcophine, a marine natural product. In our previous work, we reported the significant chemopreventive effects of SD against non-melanoma skin cancer both in vitro and in vivo mouse models. In this investigation, we extended this work to study the effect of sarcodiol on melanoma development, the more deadly form of skin cancer, using the mouse melanoma B16F10 cell line. In this study we report that SD inhibits the de novo DNA synthesis and enh...

  11. Dose-Response on the Chemopreventive Effects of Sarcophine-Diol on UVB-Induced Skin Tumor Development in SKH-1 Hairless Mice

    Directory of Open Access Journals (Sweden)

    Chandradhar Dwivedi

    2012-09-01

    Full Text Available Sarcophine-diol (SD is a lactone ring-opened analogue of sarcophine. It has shown chemopreventive effects on chemically-induced skin tumor development in female CD-1 mice, as well as in a UVB-induced skin tumor development model in hairless SKH-1 mice at a dose of 30 μg SD applied topically and 180 mJ/cm2 UVB. The objective of this study was to determine the dose-response on the chemopreventive effects of SD on SKH-1 hairless mice when exposed to a UVB radiation dose of 30 mJ/cm2. This UVB dose better represents chronic human skin exposure to sunlight leading to skin cancer than previous studies applying much higher UVB doses. Carcinogenesis was initiated and promoted by UVB radiation. Female hairless SKH-1 mice were divided into five groups. The control group was topically treated with 200 μL of acetone (vehicle, and the SD treatment groups were topically treated with SD (30 μg, 45 μg, and 60 μg dissolved in 200 μL of acetone 1 h before UVB radiation (30 mJ/cm2. The last group of animals received 60 μg SD/200 μL acetone without UVB exposure. These treatments were continued for 27 weeks. Tumor multiplicity and tumor volumes were recorded on a weekly basis for 27 weeks. Weight gain and any signs of toxicity were also closely monitored. Histological characteristics and the proliferating cell nuclear antigen (PCNA were evaluated in the mice skin collected at the end of the experiment. The dose-response study proved a modest increase in chemopreventive effects with the increase in SD dose. SD reduced the number of cells positively stained with PCNA proliferation marker in mice skin. The study also showed that SD application without UVB exposure has no effect on the structure of skin. The results from this study suggest that broader range doses of SD are necessary to improve the chemopreventive effects.

  12. Gadoxetic Acid-Enhanced MRI and Sonoelastography: Non-Invasive Assessments of Chemoprevention of Liver Fibrosis in Thioacetamide-Induced Rats with Sho-Saiko-To

    OpenAIRE

    Chen, Ya-Wen; Tsai, Meng-Yuan; Pan, Huay-Ben; Tseng, Hui-Hwa; Hung, Yu-Ting; Chou, Chen-Pin

    2014-01-01

    Background This study aimed to compare the performance of gadoxetic acid -enhanced magnetic resonance imaging (MRI) and sonoelastography in evaluating chemopreventive effects of Sho-Saiko-To (SST) in thioacetamide (TAA)-induced early liver fibrosis in rats. Materials and Methods Ten of Sprague-Dawley rats receiving TAA (200 mg/kg of body weight) intraperitoneal injection were divided into three groups: Group 1 (TAA only, n = 3), Group 2 (TAA +0.25 g/kg SST, n = 4) and Group 3 (TAA+1 g/kg SST,...

  13. The chemopreventive activity of the histone deacetylase inhibitor tributyrin in colon carcinogenesis involves the induction of apoptosis and reduction of DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Heidor, Renato [Laboratory of Diet, Nutrition and Cancer, Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo (Brazil); Advanced Research Center in Food Science and Nutrition (NAPAN) and Food Research Center (FoRC), Faculty of Pharmaceutical Sciences, University of São Paulo (Brazil); Furtado, Kelly Silva; Ortega, Juliana Festa [Laboratory of Diet, Nutrition and Cancer, Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo (Brazil); Oliveira, Tiago Franco de [Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo (Brazil); Tavares, Paulo Eduardo Latorre Martins; Vieira, Alessandra; Miranda, Mayara Lilian Paulino [Laboratory of Diet, Nutrition and Cancer, Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo (Brazil); Purgatto, Eduardo [Laboratory of Food Chemistry and Biochemistry, Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo (Brazil); Advanced Research Center in Food Science and Nutrition (NAPAN) and Food Research Center (FoRC), Faculty of Pharmaceutical Sciences, University of São Paulo (Brazil); Moreno, Fernando Salvador, E-mail: rmoreno@usp.br [Laboratory of Diet, Nutrition and Cancer, Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo (Brazil); Advanced Research Center in Food Science and Nutrition (NAPAN) and Food Research Center (FoRC), Faculty of Pharmaceutical Sciences, University of São Paulo (Brazil)

    2014-04-15

    The chemopreventive activity of the histone deacetylase inhibitor (HDACi) tributyrin (TB), a prodrug of butyric acid (BA), was evaluated in a rat model of colon carcinogenesis. The animals were treated with TB (TB group: 200 mg/100 g of body weight, b.w.) or maltodextrin (MD isocaloric control group: 300 mg/100 g b.w.) daily for 9 consecutive weeks. In the 3rd and 4th weeks of treatment, the rats in the TB and MD groups were given DMH (40 mg/kg b.w.) twice a week. After 9 weeks, the animals were euthanized, and the distal colon was examined. Compared with the control group (MD group), TB treatment reduced the total number of aberrant crypt foci (ACF; p < 0.05) as well as the ACF with ≥ 4 crypts (p < 0.05), which are considered more aggressive, but not inhibited the formation of DMH-induced O6-methyldeoxyguanosine DNA adducts. The TB group also showed a higher apoptotic index (p < 0.05) and reduced DNA damage (p < 0.05) compared with MD group. TB acted as a HDACi, as rats treated with the prodrug of BA had higher levels of histone H3K9 acetylation compared with the MD group (p < 0.05). TB administration resulted in increased colonic tissue concentrations of BA (p < 0.05) compared with the control animals. These results suggest that TB can be considered a promising chemopreventive agent for colon carcinogenesis because it reduced the number of ACF, including those that were more aggressive. Induction of apoptosis and reduction of DNA damage are cellular mechanisms that appear to be involved in the chemopreventive activity of TB. - Highlights: • Tributyrin is a chemopreventive agent for rat colon aberrant crypt foci. • Tributyrin increased apoptosis in an experimental rat colon carcinogenesis model. • Tributyrin treatment in a rat colon carcinogenesis model decreased DNA damage. • Tributyrin treatment induced H3K9 acetylation in a rat colon carcinogenesis model.

  14. 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.

  15. Sarcophine-Diol, a Skin Cancer Chemopreventive Agent, Inhibits Proliferation and Stimulates Apoptosis in Mouse Melanoma B16F10 Cell Line

    Directory of Open Access Journals (Sweden)

    Hesham Fahmy

    2011-12-01

    Full Text Available Sarcodiol (SD is a semi-synthetic derivative of sarcophine, a marine natural product. In our previous work, we reported the significant chemopreventive effects of SD against non-melanoma skin cancer both in vitro and in vivo mouse models. In this investigation, we extended this work to study the effect of sarcodiol on melanoma development, the more deadly form of skin cancer, using the mouse melanoma B16F10 cell line. In this study we report that SD inhibits the de novo DNA synthesis and enhances fragmentation of DNA. We also evaluated the antitumor effect of SD on melanoma cell viability using several biomarkers for cell proliferation and apoptosis. SD inhibits the expression levels of signal transducers and activators of transcription protein (STAT-3 and cyclin D1, an activator of cyclin-dependent kinase 4 (Cdk4. SD treatment also enhances cellular level of tumor suppressor protein 53 (p53 and stimulates cleavage of the nuclear poly (ADP-ribose polymerase (cleaved-PARP. SD also enhances cellular levels of cleaved Caspase-3, -8, -9 and stimulates enzymatic activities of Caspase-3, -8 and -9. These results, in addition to inhibition of cell viability, suggest that SD inhibits melanoma cell proliferation by arresting the cell-division cycle in a Go quiescent phase and activates programmed cell death (apoptosis via extrinsic and intrinsic pathways. Finally, these studies demonstrate that SD shows a very promising chemopreventive effect in melanoma B16F10 tumor cells.

  16. Sarcophine-diol, a skin cancer chemopreventive agent, inhibits proliferation and stimulates apoptosis in mouse melanoma B₁₆F₁₀ cell line.

    Science.gov (United States)

    Szymanski, Pawel T; Kuppast, Bhimanna; Ahmed, Safwat A; Khalifa, Sherief; Fahmy, Hesham

    2012-01-01

    Sarcodiol (SD) is a semi-synthetic derivative of sarcophine, a marine natural product. In our previous work, we reported the significant chemopreventive effects of SD against non-melanoma skin cancer both in vitro and in vivo mouse models. In this investigation, we extended this work to study the effect of sarcodiol on melanoma development, the more deadly form of skin cancer, using the mouse melanoma B₁₆F₁₀ cell line. In this study we report that SD inhibits the de novo DNA synthesis and enhances fragmentation of DNA. We also evaluated the antitumor effect of SD on melanoma cell viability using several biomarkers for cell proliferation and apoptosis. SD inhibits the expression levels of signal transducers and activators of transcription protein (STAT-3) and cyclin D1, an activator of cyclin-dependent kinase 4 (Cdk4). SD treatment also enhances cellular level of tumor suppressor protein 53 (p53) and stimulates cleavage of the nuclear poly (ADP-ribose) polymerase (cleaved-PARP). SD also enhances cellular levels of cleaved Caspase-3, -8, -9 and stimulates enzymatic activities of Caspase-3, -8 and -9. These results, in addition to inhibition of cell viability, suggest that SD inhibits melanoma cell proliferation by arresting the cell-division cycle in a Go quiescent phase and activates programmed cell death (apoptosis) via extrinsic and intrinsic pathways. Finally, these studies demonstrate that SD shows a very promising chemopreventive effect in melanoma B₁₆F₁₀ tumor cells. PMID:22363217

  17. Effect of gallic acid on xenobiotic metabolizing enzymes in 1,2-dimethyl hydrazine induced colon carcinogenesis in Wistar rats--a chemopreventive approach.

    Science.gov (United States)

    Giftson Senapathy, J; Jayanthi, S; Viswanathan, P; Umadevi, P; Nalini, N

    2011-04-01

    Colon cancer risk may be influenced by phase I and II xenobiotic-metabolizing enzyme systems. The chemopreventive agent gallic acid (GA), a plant polyphenol, is found in various natural products. Our aim was to evaluate the potential role of GA on drug-metabolizing enzymes in 1,2-dimethyl hydrazine (DMH) induced rat colon carcinogenesis. The total experimental duration was 30 weeks. The effect of GA (50 mg/kg b.w.) on the activities of phase I enzymes (cytochrome P450 and cytochrome b5) and phase II enzymes (glutathione S-transferase, DT-diaphorase and gamma glutamyl transpeptidase) were assessed in the liver and colonic mucosa and the colons were also examined visually. In DMH induced rats, there was a decrease in the activities of phase II enzymes and an increase in the activities of phase I enzymes. On GA supplementation, there was a significant increase in the activities of phase II enzymes and a significant decrease in the activities of phase I enzymes, in addition to the decreased tumor incidence. Histopathological changes also confirm this. Thus, the marked potential of GA in modulating the phase I and II xenobiotic-metabolizing enzymes suggests that GA may have a major impact on colon cancer chemoprevention. PMID:21172399

  18. Chemopreventive and Antilipidperoxidative Efficacy of Piper longum (Linn.) on 7,12-dimethylbenz (a) anthracene (DMBA) Induced Hamster Buccal Pouch Carcinogenesis

    Science.gov (United States)

    Senthil, Namasivayam; Manoharan, Shanmugam; Balakrishnan, Subramanian; Rajmani Ramachandran, Cinnamanoor; Muralinaidu, Radhakrishnan

    Aim of the present study was to find out the chemopreventive efficacy of Piper longum, a plant having diverse medicinal properties, in 7,12-dimethyl benz (a) anthracene (DMBA) induced oral carcinogenesis. The mechanistic pathway for its chemopreventive potential was analysed by measuring lipid peroxidation and antioxidants status in DMBA induced oral cancer. DMBA painting in hamster buccal pouch three times per week for 14 weeks resulted in well developed, well differentiated squamous cell carcinoma. Elevated lipid peroxidation and decline in antioxidants were noticed in tumor bearing hamsters as compared to control animals. Oral administration of ethanolic extract of Piper longum dried fruits (PLEFet) on alternate days to DMBA painting significantly prevented the tumor incidence, volume and burden and restored the status of lipid peroxidation and antioxidants in DMBA painted hamsters. Our results indicate that the dried fruits of P. longum has suppressing effects on cell proliferation, which is probably due to its antilipid peroxidative and antioxidative potential during DMBA induced oral carcinogenesis.

  19. Chemoprevention of 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster cheek pouch carcinogenesis by a 5-lipoxygenase inhibitor, garcinol.

    Science.gov (United States)

    Chen, Xin; Zhang, Xinyan; Lu, Ye; Shim, Joong-Youn; Sang, Shengmin; Sun, Zheng; Chen, Xiaoxin

    2012-01-01

    Our previous studies have shown that aberrant arachidonic acid metabolism, especially the 5-lipoxygenase (5-Lox) pathway, is involved in oral carcinogenesis and can be targeted for cancer prevention. To develop potent topical agents for oral cancer chemoprevention, 5 known 5-Lox inhibitors from dietary and synthetic sources (Zileuton, ABT-761, licofelone, curcumin, and garcinol) were evaluated in silico for their potential efficacy. Garcinol, a polyisoprenylated benzophenone from the fruit rind of Garcinia spp., was found to be a promising agent based on the calculation of a theoretical activity index. Computer modeling showed that garcinol well fit the active site of 5-Lox, and potentially inhibited enzyme activity through interactions between the phenolic hydroxyl groups and the non-heme catalytic iron. In a short-term study on 7,12-dimethylbenz[a]anthracene (DMBA)-treated hamster cheek pouch, topical garcinol suppressed leukotriene B4 (LTB4) biosynthesis and inhibited inflammation and cell proliferation in the oral epithelium. In a long-term carcinogenesis study, topical garcinol significantly reduced the size of visible tumors, the number of cancer lesions, cell proliferation, and LTB4 biosynthesis. These results demonstrated that topical application of a 5-Lox inhibitor, garcinol, had chemopreventive effect on DMBA-induced hamster cheek pouch carcinogenesis. PMID:23137051

  20. 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

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

    International Nuclear Information System (INIS)

    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

  2. Chemoprevention of mammary carcinogenesis by 1α-hydroxyvitamin D5, a synthetic analog of Vitamin D

    International Nuclear Information System (INIS)

    Numerous analogs of Vitamin D have been synthesized in recent years with the hope of generating a compound that retains the anticarcinogenic activity of Vitamin D without causing any toxicity. We synthesized such an analog, 1α-hydroxy-24-ethylcholecalciferol [1α-hydroxyvitamin D5 or 1α(OH)D5], and showed that it was tolerated by rats and mice at a much higher dose than 1α,25 dihydroxy cholecalciferol [1α,25(OH)2D3]. This property makes it a prime candidate for chemoprevention studies. In the mouse mammary gland organ culture (MMOC), 1α(OH)D5 inhibited carcinogen-induced development of both mammary alveolar and ductal lesions. In vivo carcinogenesis study showed statistically significant reduction of tumor incidence and multiplicity in N-methyl-N-nitrosourea (MNU)-treated rats that were fed 25-50 μg 1α(OH)D5/kg diet. There were no adverse effects on plasma calcium concentrations. In order to determine if the effect of 1α(OH)D5 would be selective in suppressing proliferation of transformed cells, its effects on cell growth and proliferation were compared between BT474 (cancer) and MCF12F (non-tumorigenic) human breast epithelial cells. Results showed that 1α(OH)D5 induced apoptosis and cell cycle G1 phase arrest in BT474 breast cancer cells without having any effects on proliferation of the MCF12F cells. In addition, in MMOC it had no growth inhibitory effects on normal epithelial cell proliferation in the absence of carcinogen. Similarly, non-tumorigenic human breast epithelial cells in explant culture did not respond to 1α(OH)D5, whereas treatment with 1α(OH)D5 induced cell death in the explants of cancer tissue. These results collectively indicate that 1α(OH)D5 selectively induced apoptosis only in transformed cells but not in normal breast epithelial cells. Interestingly, the growth inhibitory effects of 1α(OH)D5 were observed in Vitamin D receptor positive (VDR+) breast cancer cells, but not in highly metastatic VDR- breast cancer cells, such as

  3. Breast cancer chemoprevention

    Directory of Open Access Journals (Sweden)

    Ivana Sestak

    2011-12-01

    Full Text Available Trials with tamoxifen have clearly shown that the risk of developing oestrogen receptor positive breast cancer can be reduced by at least 50% with prophylactic agents. The current challenge is to find new agents which achieve this or better efficacy, but with fewer side effects. Recent results indicate that the SERM raloxifene has similar efficacy to tamoxifen, but leads to fewer endometrial cancers, gynecological symptoms, and thromboembolic events. Results for contralateral tumors in adjuvant trials suggest that aromatase inhibitors may be able to prevent up to 70%–80% of ER-positive breast cancers, and this is currently being investigated in two large prevention trials, one using anastrozole (IBIS-II and the other exemestane (MAP.3. New agents are needed for receptor negative breast cancer and several possibilities are currently under investigation.

  4. Exploring the Potential Role of Chemopreventive Agent, Hesperetin Conjugated Pegylated Gold Nanoparticles in Diethylnitrosamine-Induced Hepatocellular Carcinoma in Male Wistar Albino Rats.

    Science.gov (United States)

    Gokuladhas, Krishnan; Jayakumar, Subramaniyan; Rajan, Balan; Elamaran, Ramasamy; Pramila, Chengalvarayan Subramani; Gopikrishnan, Mani; Tamilarasi, Sasivarman; Devaki, Thiruvengadam

    2016-04-01

    Liver cancer is the fifth most common cancer and is still one of the leading causes of death world wide, due to food additives, alcohol, fungal toxins, air, toxic industrial chemicals, and water pollutants. Chemopreventive drugs play a potential role in liver cancer treatment. Obviously in the production of anticancer drugs, the factors like poor solubility, bioavailability, biocompatibility, limited chemical stability, large amount of dose etc., plays a major role. Against this backdrop, the idea of designing the chemopreventive nature of bio flavanoid hesperetin (HP) drug conjugated with pegylated gold nanoparticles to increasing the solubility, improve bioavailability and enhance the targeting capabilities of the drug during diethylnitrosamine (DEN) induced liver cancer in male wistar albino rats. The dose fixation studies and the toxicity of pure HP and HP conjugated gold nanoparticles (Au-mPEG(5000)-S-HP) were analysed. After concluded the dose fixation and toxicity studies the experimental design were segregated in six groups for the anticancer analysis of DEN induced HCC for 16 weeks. After the experimental period the body weight, relative liver weight, number of nodules and size of nodules, the levels of tumor markers like CEA, AFP and the level of lipid peroxidation, lipid hydroperoxides and the activities of antioxidant enzymes were assessed. The administration of DEN to rats resulted in increased relative liver weight and serum marker enzymes aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, and gamma glutamyl transpeptidase. The levels of lipid peroxides elevated (in both serum and tissue) with subsequent decrease in the final body weight and tissue antioxidants like superoxide dismutase, catalase, reduced glutathione, glutathione peroxidise, and glutathione reductase. HP supplementation (20 mg/kg b.wt) significantly attenuated these alterations, thereby showing potent anticancer effect in liver cancer and the

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

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    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.

  6. Compounds from the Fruits of the Popular European Medicinal Plant Vitex agnus-castus in Chemoprevention via NADP(H:Quinone Oxidoreductase Type 1 Induction

    Directory of Open Access Journals (Sweden)

    Shenghong Li

    2013-01-01

    Full Text Available As part of our continuing efforts in the search for potential biologically active compounds from medicinal plants, we have isolated 18 compounds including two novel nitrogen containing diterpenes from extracts of the fruits of Vitex agnus-castus. These isolates, along with our previously obtained novel compound vitexlactam A (1, were evaluated for potential biological effects, including cancer chemoprevention. Chemically, the nitrogenous isolates were found to be two labdane diterpene alkaloids, each containing an α, β-unsaturated γ-lactam moiety. Structurally, they were elucidated to be 9α-hydroxy-13(14-labden-16,15-amide (2 and 6β-acetoxy-9α-hydroxy-13(14-labden-15,16-amide (3, which were named vitexlactams B and C, respectively. The 15 known isolates were identified as vitexilactone (4, rotundifuran (5, 8-epi-manoyl oxide (6, vitetrifolin D (7, spathulenol (8, cis-dihydro-dehydro-diconiferylalcohol-9-O-β-D-glucoside (9, luteolin-7-O-glucoside (10, 5-hydroxy-3,6,7,4′-tetramethoxyflavone (11, casticin (12, artemetin (13, aucubin (14, agnuside (15, β-sitosterol (16, p-hydroxybenzoic acid (17, and p-hydroxybenzoic acid glucose ester (18. All compound structures were determined/identified on the basis of 1D and/or 2D NMR and mass spectrometry techniques. Compounds 6, 8, 9, and 18 were reported from a Vitex spieces for the first time. The cancer chemopreventive potentials of these isolates were evaluated for NADP(H:quinone oxidoreductase type 1 (QR1 induction activity. Compound 7 demonstrated promising QR1 induction effect, while the new compound vitexlactam (3 was only slightly active.

  7. Evaluation of chemopreventive effect ofFumaria indica against N-nitrosodiethylamine and CCl4-induced hepatocellular carcinoma in Wistar rats

    Institute of Scientific and Technical Information of China (English)

    Talib Hussain; Hefazat H Siddiqui; Sheeba Fareed; M Vijayakumar; Chandana V Rao

    2012-01-01

    Objective:To investigation the chemopreventive potential ofFumaria indica (F. indica) extract (FIE) on N-nitrosodiethylamine and CCl4-induced hepatocarcinogenesis in Wistar rats.Methods:The experimental animals were divided into six groups (n=6). Hepatocellular carcinoma was induced by single intraperitoneal injection ofN-nitrosodiethylamine (NDEA) in normal saline at a dose of 200 mg/kg body weight followed by weekly subcutaneous injections of CCl4 (3 mL/kg/week) for 6 weeks, as the promoter of carcinogenic effect. After administration of the carcinogen, 200 and 400 mg/kg of FIE were administered orally once a day throughout the study. At the end of 20 weeks, the body weight, liver weight and relative liver weight were measured. The percentage of nodule incidence and liver cancer markers such as aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP),γ-glutamyl transferase (γ-GT), total bilirubin level (TBL), α-feto protein (AFP) and carcinoembryonic antigen were estimated along with histopathological investigation in experimental groups of rats. Results: Obtained results demonstrated that the cotreatment with FIE significantly prevented the decrease of the body weight and also increased in relative liver weight caused by NDEA. The treatment with FIE significantly reduced the nodule incidence and nodule multiplicity in the rats after NDEA administration. The levels of liver cancer markers such as AST, ALT, ALP,γ-glutamyl transferase, TBL, AFP and carcinoembryonic antigen were substantially increased by NDEA treatment. However, FIE treatment significantly reduced the liver injury and restored the entire liver cancer markers. Histological observations of liver tissues too correlated with the biochemical observations.Conclusions: These finding powerfully supports thatF. indica exert chemopreventive effect by suppressing the tumor burden and restoring the activities of hepatic cancer marker enzymes on NDEA and CCl4-induced

  8. 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.

  9. Evaluation of chemopreventive response of two cycloxygenase-2 inhibitors, etoricoxib and diclofenac in rat colon cancer using FTIR and NMR spectroscopic techniques Evaluación de la respuesta quimiopreventiva de dos inhibidores de la ciclooxigenasa 2, etoricoxib y diclofenaco en el cáncer de colon murino empleando las técnicas espectroscópicas FTIR Y NMR

    OpenAIRE

    M. Kaur Saini; S. Nath Sanyal

    2010-01-01

    Non steroidal anti inflammatory drugs (NSAIDs) are efficacious in chemoprevention of colorectal cancer. Therefore, the potential ability of Etoricoxib, a selective cycloxygenase-2(COX-2) inhibitor and Diclofenac, a preferential COX-2 inhibitor are considered in the chemoprevention of 1, 2-dimethylhydrazine (DMH) induced colon carcinogenesis in rat model. DMH was injected s.c. for six weeks while Etoricoxib and Diclofenac were fed daily orally alone and also in combination with an weekly subcu...

  10. Chemoprevention by celecoxib in reflux-induced gastric adenocarcinoma in Wistar rats that underwent gastrojejunostomy Quimioprevenção pelo celecoxibe no adenocarcinoma gástrico induzido por refluxo em ratos Wistar submetidos à gastrojejunostomia

    OpenAIRE

    Valéria Costa; Frederico Theobaldo Ramos Rocha; Laercio Gomes Lourenço; Mário Jorge Jucá; Antenor Teixeira Leal

    2009-01-01

    PURPOSE: To evaluate chemoprevention by celecoxib in cases of reflux-induced gastric adenocarcinoma, in Wistar rats that underwent gastrojejunostomy. METHODS: Sixty male Wistar rats of average age three months underwent surgery and were distributed into three groups: group 1, exploratory laparotomy; group 2, gastrojejunostomy; and group 3, gastrojejunostomy and daily celecoxib administration. After 53 weeks, the animals were sacrificed. Changes in the mucosa of the gastric body of group 1 and...

  11. Chemopreventive effects of early-stage and late-stage supplementation of vitamin E and selenium on esophageal carcinogenesis in rats maintained on a low vitamin E/selenium diet

    OpenAIRE

    Yang, Hui; Fang, Jin; Jia, Xudong; Han, Chi; Chen, Xiaoxin; Yang, Chung S; Li, Ning

    2010-01-01

    Low vitamin E and selenium (Ve/Se) nutritional status is known to be associated with increased risk of esophageal squamous cell carcinoma (ESCC). A previous human intervention trial demonstrated that Ve/Se supplementation decreased the occurrence of esophageal cancer death among younger participants but not among older ones. In this study, we intended to mimic this human nutritional status to determine the chemopreventive effects of Ve/Se supplementation at the early or late stage of esophage...

  12. Evaluation of 3-(4'-(4″-fluorophenyl)-6'-phenylpyrimidin-2'-yl)-2-phenylthiazolidin-4-one for in vivo modulation of biomarkers of chemoprevention in the 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis.

    Science.gov (United States)

    Thanusu, J; Kanagarajan, V; Nagini, S; Gopalakrishnan, M

    2011-06-01

    A new bis heterocycle comprising both bioactive 2-aminopyrimidine and thiazolidin-4-one nuclei namely 3-(4'-(4″-fluorophenyl)-6'-phenylpyrimidin-2'-yl)-2-phenylthiazolidin-4-one 3 was synthesized, characterized with the help of melting point, elemental analysis, FT-IR, MS, one-dimensional NMR ((1)H, (13)C) spectra and we evaluated the chemopreventive potential of 3-(4'-(4″-fluorophenyl)-6'-phenylpyrimidin-2'-yl)-2-phenylthiazolidin-4-one based on in vivo inhibitory effects on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Administration of 3 effectively suppressed oral carcinogenesis initiated with DMBA as revealed by the reduced incidence of neoplasms. Lipid peroxidation, glutathione (GSH) content, and the activities of glutathione peroxidase (GPx), glutathione S-transferase (GST) were used to biomonitor the chemopreventive potential of 3. Lipid peroxidation was found to be significantly decreased, whereas GSH, GPx, GST, and GGT were elevated in the oral mucosa of tumor-bearing animals. Our data suggest that 3 may exert its chemopreventive effects in the oral mucosa by modulation of lipid peroxidation and enhancing the levels of GSH, GPx, and GST. PMID:21028942

  13. Chemopreventive effects of Frondanol A5, a Cucumaria frondosa extract, against rat colon carcinogenesis and inhibition of human colon cancer cell growth.

    Science.gov (United States)

    Janakiram, Naveena B; Mohammed, Altaf; Zhang, Yuting; Choi, Chang-In; Woodward, Carl; Collin, Peter; Steele, Vernon E; Rao, Chinthalapally V

    2010-01-01

    Sea cucumber extracts have been widely used to treat individuals with inflammatory conditions in East Asia. The present study has been designed to test potential colon cancer-preventive properties of Frondanol A5, a glycolipid extract from the sea cucumber, Cucumaria frondosa, using in vivo and in vitro models of colon cancer. Chemopreventive efficacy of Frondanol A5 was evaluated on azoxymethane-induced rat colon carcinogenesis using colonic aberrant crypt foci (ACF) as efficacy marker. At 7 weeks of age, groups of rats (12 per group) were fed the AIN-76A diet, and ACFs were induced by azoxymethane (15 mg/kg body weight). Three days after azoxymethane treatment, rats were fed with the diets containing 0, 150, and 450 ppm of Frondanol A5 and continued on the diets for 8 weeks, at which time ACFs were evaluated. Expression levels of proliferating cell nuclear antigen and p21(WAF1/CIP1) were determined in ACFs. Further, Frondanol A5 (10-120 microg/mL) was studied for its growth-inhibitory and apoptotic effects in the HCT-116 cell line. Dietary administration of 150 and 450 ppm of Frondanol A5 significantly suppressed azoxymethane-induced total colonic ACF formation, approximately 34% to 55% (P < 0.01 to P < 0.0001), and multicrypt aberrant foci (48-68.5%, P < 0.0001) in a dose-dependent manner. ACFs in rats treated with Frondanol A5 showed significant upregulation of p21(WAF1/CIP1) and downregulation of proliferating cell nuclear antigen compared with control group. Frondanol A5 showed growth inhibition at S and G(2)-M phase with a decrease in Cdc25c and an increase in p21(WAF1/CIP) with significant apoptosis associated with H2AX phosphorylation and caspase-2 cleavage in HCT116 cells. Overall, Frondanol A5 exhibits potential chemopreventive properties for colon carcinogenesis, which suggests further development of this sea cucumber extract. PMID:20051375

  14. Natural dietary anti-cancer chemopreventive compounds: redox-mediated differential signaling mechanisms in cytoprotection of normal cellsversus cytotoxicity in tumor cells

    Institute of Scientific and Technical Information of China (English)

    Sujit NAIR; Wenge LI; Ah-Ng Tony KONG

    2007-01-01

    Many dietary phytochemicals exhibit health-beneficial effects including preven-tion of diseases such as cancer, as well as neurological, cardiovascular, inflam-matory, and metabolic diseases. Evolutionarily, herbivorous and omnivorous animals have been ingesting plants. This interaction between "animal-plant"ecosystems has resulted in an elaborate system of detoxification and defense mechanisms evolved by animals including humans. Mammalian cells, including human cells, respond to these dietary phytochemicals by "non-classical receptor sensing" mechanisms of electrophilic chemical-stress typified by "thiol-modu-lated" cellular signaling events primarily leading to the gene expression of phar-macologically beneficial effects, but sometimes unwanted cytotoxicity also. Our laboratory has been studying two groups of dietary phytochemical cancer-chemopreventive compounds (isothiocyanates and polyphenols), which are effective in chemical-induced, as well as genetically-induced, animal carcinogen-esis models. These compounds typically generate "cellular stress" and modulate gene expression of phase Ⅱ detoxifying/antioxidant enzymes. Electrophiles, reac-tive oxygen species, and reactive nitrogen species are known to act as second messengers in the modulation of many cellular signaling pathways leading to gene expression changes and pharmacological responses. Redox-sensitive tran-scription factors such as nuclear factor-E2-related factor 2 (Nrf2), AP-1, NF-κB, to cite a few examples, sense and transduce changes in the cellular redox status and modulate gene expression responses to oxidative and electrophilic stresses, pre-sumably via sulfhydryl modification of critical cysteine residues found on these proteins and/or other upstream redox-sensitive molecular targets. In the current review, we will explore dietary cancer chemopreventive phytochemicals, discuss the link between oxidative/electrophilic stresses and the redox circuitry, and con-sider different redox

  15. 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

  16. Localized sequence-specific release of a chemopreventive agent and an anticancer drug in a time-controllable manner to enhance therapeutic efficacy.

    Science.gov (United States)

    Pan, Wen-Yu; Lin, Kun-Ju; Huang, Chieh-Cheng; Chiang, Wei-Lun; Lin, Yu-Jung; Lin, Wei-Chih; Chuang, Er-Yuan; Chang, Yen; Sung, Hsing-Wen

    2016-09-01

    Combination chemotherapy with multiple drugs commonly requires several injections on various schedules, and the probability that the drug molecules reach the diseased tissues at the proper time and effective therapeutic concentrations is very low. This work elucidates an injectable co-delivery system that is based on cationic liposomes that are adsorbed on anionic hollow microspheres (Lipos-HMs) via electrostatic interaction, from which the localized sequence-specific release of a chemopreventive agent (1,25(OH)2D3) and an anticancer drug (doxorubicin; DOX) can be thermally driven in a time-controllable manner by an externally applied high-frequency magnetic field (HFMF). Lipos-HMs can greatly promote the accumulation of reactive oxygen species (ROS) in tumor cells by reducing their cytoplasmic expression of an antioxidant enzyme (superoxide dismutase) by 1,25(OH)2D3, increasing the susceptibility of cancer cells to the cytotoxic action of DOX. In nude mice that bear xenograft tumors, treatment with Lipos-HMs under exposure to HFMF effectively inhibits tumor growth and is the most effective therapeutic intervention among all the investigated. These empirical results demonstrate that the synergistic anticancer effects of sequential release of 1,25(OH)2D3 and DOX from the Lipos-HMs may have potential for maximizing DOX cytotoxicity, supporting more effective cancer treatment. PMID:27294541

  17. 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

  18. Chemopreventive Effect of Dietary Glutamineon Colitis-Associated Colorectal Cancer Is Associated with Modulation of the DEPTOR/mTOR Signaling Pathway.

    Science.gov (United States)

    Tian, Yun; Wang, Keming; Fan, Yingrui; Wang, Yan; Sun, Liqun; Wang, Li; Wang, Jirong; Wang, Zhaoxia; Li, Juan; Ye, Ying; Ji, Guozhong

    2016-01-01

    Glutamine plays a protective role in colitis and colitis-associated colorectal cancer (CAC); however, the protective mechanisms are largely unknown to date. DEP domain-containing mTOR-interacting protein (DEPTOR)/mammalian Target of Rapamycin (mTOR) signaling plays an important role in carcinogenesis. The present study investigated the potential molecular mechanisms for the protective effect of glutamine in a murine model of azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CAC. The effects of glutamine on DEPTOR/mTOR signaling and protein light chain 3 (LC3) were evaluated. Administration of glutamine was associated with attenuated development of CAC. Increased expression of DEPTOR and decreased expressions of factors of mTOR signaling, including phospho-mTOR, phospho-STAT3, phospho-Akt, and phospho-S6, were observed in AOM/DSS mice administered glutamine. Furthermore, oral glutamine was associated with increased LC3-II expression in AOM/DSS mice. The present study indicates that regulation of DEPTOR/mTOR signaling may be an important mechanism for glutamine in prevention against the development of CAC. In addition, the chemopreventive effect of dietary glutamine on CAC is, at least in part, associated with the induction of autophagy. PMID:27144580

  19. Warfarin and coumarin-like Murraya paniculata extract down-regulate EpCAM-mediated cell adhesion: individual components versus mixture for studying botanical metastatic chemopreventives.

    Science.gov (United States)

    Shao, Jingwei; Zhou, Suxia; Jiang, Zhou; Chi, Ting; Ma, Ji; Kuo, Minliang; Lee, Alan Yueh-Luen; Jia, Lee

    2016-01-01

    We recently defined cancer metastatic chemoprevention as utilizing safe and effective molecules to comprehensively prevent the spark of activation-adhesion-extravasation-proliferation metastatic cascade caused by circulating tumor cells (CTCs). The strategy focuses on preventing the most important starting point of the cascade. We identified an extract from a well-known medical plant Murraya paniculata, which inhibited both embryonic implantation to human endometrium as traditionally-used for abortion and CTC adhesion to human endothelium. Here, we separated and characterized five coumarin-containing components (Z1-Z5) from the botanic extract. Flow cytometry revealed that within 1-100 μg/mL, Z3 and Z5 down-regulated EpCAM expression in human colon HCT116, whereas, Z1 and Z2 did oppositely. Warfarin and Z1-Z5 component mixture (CM) also down-regulated EpCAM expression. The down-regulation of EpCAM by Z3, Z5, CM and warfarin was confirmed by western blotting, and caused inhibition on adhesion of cancer cells to human endothelial cells. Rat coagulation study showed that warfarin prolonged prothrombin time, whereas, Z3 did not. The present studies revealed that, for the first time, warfarin and coumarin-like components Z3, Z5 and CM from Murraya paniculata could directly inhibit EpCAM-mediated cell-cell adhesion. PMID:27480614

  20. 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

    International Nuclear Information System (INIS)

    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

  1. Antineoplastic effect of a novel chemopreventive agent, neokestose, on the Caco-2 cell line via inhibition of expression of nuclear factor-κB and cyclooxygenase-2.

    Science.gov (United States)

    Lee, Shun-Mei; Chang, Jan-Yi; Wu, Jiann-Shing; Sheu, Dey-Chyi

    2015-07-01

    Neokestose is a 6G-fructooligosaccharide (FOS) and an important prebiotic. When FOS are ingested by patients with colorectal cancer, they may come into contact with cancer cells prior to being fermented by bifidobacteria in the colon. In the present study, the effects of neokestose on cell proliferation, cell cycle and apoptosis of the colorectal cancer cell line Caco-2 were investigated to evaluate its anti-cancer effect. An MTT assay showed that neokestose-treated Caco-2 cells exhibited a significant and dose-dependent loss of viability. Flow cytometric analysis indicated that the sub-G1 population of Caco-2 cells was significantly increased following treatment with neokestose, and the percentage of Caco-2 cells in the stage of late apoptosis was also significantly increased in a dose-dependent manner. Western blot analysis showed that the overexpression of nuclear factor-κB, a central molecule responsible for the transition from inflammation to cancer, and cyclooxygenase-2, an important enzyme in colorectal tumorigenesis, in colorectal carcinoma cells was inhibited by neokestose. Accordingly, the present study provided in vitro evidence that neokestose may be used as a dietary chemopreventive agent, whose application is more rational than that of COX-2 inhibitors or aspirin for preventing colorectal cancer. PMID:25815878

  2. 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.

  3. 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

  4. A six-month crossover chemoprevention clinical trial of tea in smokers and non-smokers: methodological issues in a feasibility study

    Directory of Open Access Journals (Sweden)

    Dash Chiranjeev

    2012-07-01

    Full Text Available Abstract Background Chemoprevention crossover trials of tea can be more efficient than parallel designs but the attrition and compliance rates with such trials are unknown. Methods Attrition (dropouts and compliance with treatment were assessed in a 25-week randomized, placebo controlled, crossover, feasibility clinical trial of four tea treatments to investigate the effect of tea on oral cancer biomarkers. Each treatment lasted 4 weeks with 2 weeks of washout in between. Participants were 32 smokers and 33 non-smokers without any evidence of premalignant oral lesions. The interventions consisted of packets of green tea, black tea, caffeinated water, or placebo. Participants were assigned to each treatment for four weeks, and were instructed to drink five packets per day while on the treatment. Dropout from the trial and compliance (consumption of ≥ 85% of the prescribed treatment packets are the main outcome measures reported. Results There was a high rate of dropout (51% from the study, and the rates were significantly higher among smokers (64% than non-smokers (36%. Among participants who completed the study the rate of compliance was 72%. The highest rates of dropouts occurred between the first and second treatment visits in both smokers (38% dropout and non-smokers (18% dropout. Throughout the study smokers were more likely to dropout than non-smokers. Black tea treatment was associated with the highest rates of dropout among smokers (37%, but was associated with the lowest rate of dropout among non-smokers (4%. Conclusions In a study conducted to test the feasibility of a four-treatment crossover tea trial, a high rate of dropout among smokers and non-smokers was observed. Multi-arm crossover tea trials might pose a higher burden on participants and research is needed to improve adherence and treatment compliance in such trials. Trial registration number ISRCTN70410203

  5. 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.

  6. Lactobacillus rhamnosus GG influences polyamine metabolism in HGC-27 gastric cancer cell line: a strategy toward nutritional approach to chemoprevention of gastric cance.

    Science.gov (United States)

    Linsalata, M; Cavallini, A; Messa, C; Orlando, A; Refolo, M G; Russo, F

    2010-01-01

    Chemoprevention by dietary constituents has recently emerged as a novel approach to control gastric cancer incidence. Over the past years, functional foods and food supplements, especially probiotics, have received much attention as potential dietary cancer prevention agents. The precise mechanisms by which these lactic cultures exert their antitumorigenic activities are not fully elucidated, but there is some evidence of their influence on cell proliferation and growth. Ornithine decarboxylase (ODC) and spermidine/spermine N1-acetyltransferase (SSAT) are the key enzymes involved in polyamine biosynthesis and catabolism, respectively. These polycationic compounds are significantly associated with cancer risk and represent a specific markers for neoplastic proliferation. The aim of this study was to investigate the effects of increasing concentrations of Lactobacillus rhamnosus strain GG (ATCC 53103) (L. GG) homogenate on polyamine biosynthesis and polyamine degradation as well as on resulting polyamine levels in HGC-27 human gastric cancer cells. The influence of this probiotic on cell proliferation was also evaluated. Administration of probiotic homogenate significantly reduced both ODC mRNA and activity as well as polyamine content and neoplastic proliferation. Besides, an increase in both SSAT mRNA and activity occurred after LGG administration in HGC-27. These data suggest that a nutritional component such as the probiotic L. GG could be proposed in an alternative approach to prevention of gastric cancer. This strategy could overcome the limitations due to a prolonged use of drugs and/or the occurrence of their adverse effects, and it could reasonably also start at a young age. PMID:20388096

  7. Expression of MRP1 and GSTP1-1 modulate the acute cellular response to treatment with the chemopreventive isothiocyanate, sulforaphane.

    Science.gov (United States)

    Sibhatu, Mebrahtu B; Smitherman, Pamela K; Townsend, Alan J; Morrow, Charles S

    2008-04-01

    A major component of the anticarcinogenic activity of the dietary chemopreventive agent sulforaphane (SFN) is attributed to its ability to induce expression of phase II detoxification genes containing the antioxidant response element (ARE) within their promoters. Because SFN is a reactive electrophile--readily forming conjugates with glutathione (GSH)--we asked whether expression of glutathione S-transferase (GST) P1-1 and the GSH conjugate efflux pump, multidrug resistance or resistance-associated protein (MRP) 1, would significantly modify the cellular response to SFN exposure. This was investigated using GST- and MRP1-poor parental MCF7 cells and transgenic derivatives expressing GSTP1-1 and/or MRP1. Compared with parental cells, expression of GSTP1-1 alone enhanced the rate of intracellular accumulation of SFN and its glutathione conjugate, SFN-SG--an effect that was associated with increased ARE-containing reporter gene induction. Expression of MRP1 greatly reduced SFN/SFN-SG accumulation and resulted in significant attenuation of SFN-mediated induction of ARE-containing reporter and endogenous gene expression. Coexpression of GSTP1-1 with MRP1 further reduced the level of induction. Depletion of GSH prior to SFN treatment or the substitution of tert-butylhydroquinone for SFN abolished the effects of MRP1/GSTP1-1 on ARE-containing gene induction-indicating that these effects are GSH dependent. Lastly, analysis of NF-E2-related factor 2 (Nrf2)--a transcription factor operating via binding to the ARE--showed that the increased levels of Nrf2 following SFN treatment were considerably less sustained in MRP1-expressing, especially those coexpressing GSTP1-1, than in MRP1-poor cells. These results suggest that the regulating effects of MRP1 and GSTP1-1 expression on SFN-dependent induction of phase II genes are ultimately mediated by altering nuclear Nrf2 levels. PMID:18204073

  8. Direct reduction of N-acetoxy-PhIP by tea polyphenols: a possible mechanism for chemoprevention against PhIP-DNA adduct formation

    International Nuclear Information System (INIS)

    The chemopreventive effect of tea against 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-DNA adduct formation and its mechanism were studied. Rats were exposed to freshly prepared aqueous extracts of green tea (3% (w/v)) as the sole source of drinking water for 10 days prior to administration with a single dose of PhIP (10 mg/kg body weight) by oral gavage. PhIP-DNA adducts in the liver, colon, heart, and lung were measured using the 32P-postlabelling technique. Rats pre-treated with tea and given PhIP 20 h before sacrifice had significantly reduced levels of PhIP-DNA adducts as compared with controls given PhIP alone. The possible mechanism of protective effect of tea on PhIP-DNA adduct formation was then examined in vitro. It was found that an aqueous extract of green and black tea, mixtures of green and black tea polyphenols, as well as purified polyphenols could strongly inhibit the DNA binding of N-acetoxy-PhIP, a putative ultimate carcinogen of PhIP formed in vivo via metabolic activation. Among these, epigallocatechin gallate was exceptionally potent. HPLC analyses of these incubation mixtures containing N-acetoxy-PhIP and the tea polyphenols each revealed the production of the parent amine, PhIP, indicating the involvement of a redox mechanism. In view of the presence of relatively high levels of tea polyphenols in rat and human plasma after ingestion of tea, this study suggests that direct reduction of the ultimate carcinogen N-acetoxy-PhIP by tea polyphenols is likely to be involved in the mechanism of chemoprotection of tea against this carcinogen

  9. Chemoprevention of 7, 12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamster cheek pouch by topical application of a dual inhibitor of epidermal growth factor receptor (EGFR) and ErbB2 tyrosine kinases

    OpenAIRE

    Sun, Zheng; Sood, Sandeep; Li, Ning; Yang, Peiying; Newman, Robert A.; Yang, Chung S.; Chen, Xiaoxin

    2007-01-01

    Oral cancer is a common neoplasm worldwide with tobacco and alcohol being the major etiological factors contributing to its pathogenesis. Epidermal growth factor receptor (EGFR) and ErbB2 are known to be involved in the development of oral cancer with the former up-regulated in up to 90% human cases. The goal of this study was to evaluate the chemopreventive effects of a dual inhibitor of EGFR and ErbB2 tyrosine kinases, GW2974, in the 7, 12-dimethylbenz[a]anthracene (DMBA)-induced hamster ch...

  10. Chemopreventive response of diclofenac, a non-steroidal anti-inflammatory drug in experimental carcinogenesis Respuesta quimiopreventiva del diclofenaco, un fármaco antiinflamatorio no esteroideo en la carcinogénesis de colon experimental

    OpenAIRE

    M. Kaur Saini; J Kaur; Sharma, P.; S. Nath Sanyal

    2009-01-01

    The chemopreventive response was evaluated of nonsteroidal anti-inflammatory drug, Diclofenac, a preferential cyclooxygenase-2 (COX-2) inhibitor in 1,2-dimethyhydrazine (DMH)-induced colon cancer in rat model. The signs of neoplasm were evident in the animals receiving 30mg of DMH per kg body weight in a weekly s.c injection for six weeks. The putative biomarker of carcinogenesis was visible in the form of multiple plaque lesions in DMH treatment and then regression seen in those animals whic...

  11. Combinatorial chemopreventive effect of butyric acid, nicotinamide and calcium glucarate against the 7,12-dimethylbenz(a)anthracene induced mouse skin tumorigenesis attained by enhancing the induction of intrinsic apoptotic events.

    Science.gov (United States)

    Tiwari, Prakash; Sahay, Satya; Pandey, Manuraj; Qadri, Syed S Y H; Gupta, Krishna P

    2015-01-25

    We explored the basis of the combinatorial chemopreventive effect of butyric acid (BA), nicotinamide (NA) and calcium glucarate (CAG) on mouse skin exposed to 7,12-dimethylbenz(a)anthracene (DMBA). We studied the effects of topical application of DMBA in the presence or absence of BA, NA and CAG on the regulators of apoptosis. DMBA treatment suppressed Bax, Bax/Bcl-2 ratio, release of cyt c, Apaf1, caspase-9, -3 mediated apoptosis. Downregulation of p21 and upregulation of Bcl-2, mut p53 were also observed in only DMBA treated mice. Simultaneous application of BA, NA and CAG induced a mitochondria-mediated apoptosis, characterized by a rise in the Bax, Bax/Bcl-2 ratio, release of cyt c, upregulation of Apaf1 with down-stream activation of caspase-9, -3. Furthermore treatment with BA, NA and CAG demonstrated an upregulation of p21 and downregulation of Bcl-2, mut p53. But this effect was enhanced in the presence of all the three compounds together in combination. Chemoprevention by a combination of BA, NA and CAG by inducing the apoptosis, the natural cell death, suggest the importance of the potential combinational strategies capable of preventing skin tumor development. PMID:25478867

  12. Medicinal Plants and Cancer Chemoprevention

    OpenAIRE

    Desai, Avni G.; Qazi, Ghulam N; Ganju, Ramesh K.; El-Tamer, Mahmoud; Singh, Jaswant; Saxena, Ajit K; Bedi, Yashbir S; Taneja, Subhash C.; Bhat, Hari K.

    2008-01-01

    Cancer is the second leading cause of death worldwide. Although great advancements have been made in the treatment and control of cancer progression, significant deficiencies and room for improvement remain. A number of undesired side effects sometimes occur during chemotherapy. Natural therapies, such as the use of plant-derived products in cancer treatment, may reduce adverse side effects. Currently, a few plant products are being used to treat cancer. However, a myriad of many plant produc...

  13. 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. PMID:26561056

  14. Chemopreventive Action of Cruciferous Vegetables

    OpenAIRE

    Janssen, Matthew

    1998-01-01

    Cancer is a tremendous health concern in the United States; incidence is high, treatment techniques are often dangerous, ineffective, and, as must be considered in this age, expensive. Increasingly, interest is turning to means of cancer prevention. Epidemiological studies have suggested that one of the most important controllable determinants of cancer risk for an individual is his or her diet; it is an important etiology in 30-60% of varieties of cancers. Of the many foods that appear to ha...

  15. Flavonol-rich fractions of yaupon holly leaves (Ilex vomitoria, Aquifoliaceae) induce microRNA-146a and have anti-inflammatory and chemopreventive effects in intestinal myofibroblast CCD-18Co cells.

    Science.gov (United States)

    Noratto, Giuliana D; Kim, Youngmok; Talcott, Stephen T; Mertens-Talcott, Susanne U

    2011-06-01

    Polyphenolics extracted from yaupon holly (Ilex vomitoria, Aquifoliaceae) (YH) leaves were investigated in human colon cells for their chemopreventive and anti-inflammatory activities. An activity-guided fractionation allowed the selection of YH flavonol-rich fraction due to its preferential inhibition of HT-29 colon cancer viability over the normal CCD-18Co colon cells. Quercetin and kaempferol 3-rutinosides, main components identified in this fraction, protected CCD-18Co cells against reactive oxidative species (ROS) in part due to increased activity of antioxidant enzymes. In addition, up-regulation of microRNA-146a (miR-146a) known as a negative regulator of pro-inflammatory NF-κB activation was the underlying molecular mechanism that protected CCD-18Co from inflammation. PMID:21262328

  16. 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.

  17. 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.

  18. Chemopreventive response of diclofenac, a non-steroidal anti-inflammatory drug in experimental carcinogenesis Respuesta quimiopreventiva del diclofenaco, un fármaco antiinflamatorio no esteroideo en la carcinogénesis de colon experimental

    Directory of Open Access Journals (Sweden)

    M. Kaur Saini

    2009-12-01

    Full Text Available The chemopreventive response was evaluated of nonsteroidal anti-inflammatory drug, Diclofenac, a preferential cyclooxygenase-2 (COX-2 inhibitor in 1,2-dimethyhydrazine (DMH-induced colon cancer in rat model. The signs of neoplasm were evident in the animals receiving 30mg of DMH per kg body weight in a weekly s.c injection for six weeks. The putative biomarker of carcinogenesis was visible in the form of multiple plaque lesions in DMH treatment and then regression seen in those animals which also received an oral dose of Diclofenac, 8 mg/kg body weight whereas no such macroscopic neoplastic lesions were seen in the animals receiving Diclofenac only or the control animals receiving the vehicle of the drug. Histopathological results showed the presence of early aberrant changes in the form of severe dysplasia and also numerous crypt fissions in the apical surface of the colonic mucosa. A very high expression of COX-2 was seen in the colonic epithelium of DMH-treated rats, as analyzed by immunohistochemistry. Also, the apoptotic events were assessed by terminal deoxynucleotidyl dUTP nick end labeling (TUNEL assay, where the DMH group shows few number of TUNEL positive cells which dramatically increased in the Diclofenac treatment. The results suggest that Diclofenac could be an effective chemopreventive agent in colon cancer, where perhaps apoptosis plays a very dominant end effect in cancer cell killings.Se evaluó la respuesta quimiopreventiva del fármaco antiinflamatorio no esteroideo, diclofenaco, un inhibidor preferente de la ciclooxigenasa-2 (Cox-2, en el cáncer de colon inducido por 1,2-dimetilhidracina (DMH en un modelo de rata. Los signos de neoplasia fueron evidentes en los animales que recibieron 30 mg de DMH por kg de peso corporal mediante inyecciones s.c. semanales durante 6 semanas. El biomarcador putativo de la carcinogénesis fue visible en la forma de múltiples lesiones en placas con el tratamiento de DMH y la posterior regresi

  19. Assessment of Augmented Immune Surveillance and Tumor Cell Death by Cytoplasmic Stabilization of p53 as a Chemopreventive Strategy of 3 Promising Medicinal Herbs in Murine 2-Stage Skin Carcinogenesis.

    Science.gov (United States)

    Ali, Farrah; Khan, Rehan; Khan, Abdul Quaiyoom; Lateef, Md Abdul; Maqbool, Tahir; Sultana, Sarwat

    2014-07-01

    Cancer is the final outcome of a plethora of events. Targeting the proliferation or inducing programmed cell death in a proliferating population is a major standpoint in the cancer therapy. However, proliferation is regulated by several cellular and immunologic processes. This study reports the inhibition of proliferation by augmenting immune surveillance, silencing acute inflammation, and inducing p53-mediated apoptosis of skin cancer by 3 promising medicinal extracts. We used the well-characterized model for experimental skin carcinogenesis in mice for 32 weeks to study the chemopreventive effect of the methanolic extracts of Trigonella foenumgraecum, Eclipta alba, and Calendula officinalis. All 3 extracts reduced the number, incidence, and multiplicity of tumors, which was confirmed by the pathologic studies that showed regressed tumors. There was a significant reduction in the PCNA+ nuclei in all treatment groups 32 weeks after the initiation. Mechanistic studies revealed that proliferative population in tumors is diminished by the restoration of the endogenous antioxidant defense, inhibition of the stress-related signal-transducing element NFκB, reduction of inflammation, enhancement of immunosurveillance of the genetically mutated cells, along with silencing of the cell cycle progression signals. Finally, all 3 medicinal extracts induced stable expression of p53 within the tumors, confirmed by the CFDA-Cy3 apoptosis assay. Results of our study confirm that these extracts not only limit the rate of proliferation by inhibition of the processes integral to cancer development but also induce stable cytoplasmic expression of p53-mediated apoptosis, leading to fewer and regressed tumors in mice. PMID:24363284

  20. 5α还原酶抑制剂在前列腺癌化学预防中的作用%Role of 5α-reductase Inhibitors in the Chemoprevention of Prostate Cancer

    Institute of Scientific and Technical Information of China (English)

    安超; 徐涛; 王晓峰

    2011-01-01

    Prostate cancer is one of the most common visceral malignancies in human. In recent years, its incidence has dramatically increased in China. 5a-reductase inhibitors can block the biological effects of dihydrotestesterone by restraining the transformation from testosterone to dihydrotestesterone, and therefore can be used for the chemoprevention of prostate cancer. Two large clinical trials on the chemopreven-ticn of prostate cancer (the Prostate Capcer Prevention Trial and the Reduction by Dutasteride of Prostate Cancer Events) were completed in 2003 and 2008 , respectively, bringing the global interests on this topic. However, the interpretations of these two trials and the possible recommendations on clinical applications remain controversial.%前列腺癌是人类最常见的内脏恶性肿瘤之一,近年我国的发病率呈逐年上升趋势,5α还原酶抑制剂通过抑制睾酮向二氢睾酮的转化,阻断二氢睾酮的生物学效应,因此可以作为前列腺癌的化学预防药物.完成于2003年及2008年的全世界最大规模的两项关于前列腺癌化学预防的大型临床试验——前列腺癌预防试验和度他雄胺减少前列腺癌事件试验,带来了前所未有的对前列腺癌化学预防的关注,但是学术界对上述试验的结论以及应该给予患者怎样的建议仍然存在争论.

  1. 芥菜籽预防化学诱导小鼠大肠肿瘤的实验研究%The experimental study on chemopreventive effect of mustard seed on chemically induced colorectal tumor in mice

    Institute of Scientific and Technical Information of China (English)

    李新艳; 郭文; 袁海锋; 邱恩祺; 袁葵

    2013-01-01

    目的 评价芥菜籽(MS)对氧化偶氮甲烷(AOM)诱导的小鼠大肠肿瘤的预防作用及其机制.方法 选择60只昆明种小鼠,随机均分为AOM模型组、AOM+5% MS干预组、AOM +10% MS干预组和正常对照组(生理盐水).记录各组小鼠有无肿瘤发生及发生数目、大小和位置,计算平均肿瘤数和肿瘤发生率;HE染色确定肿瘤的组织学类型;免疫组化染色检测肿瘤组织中PCNA蛋白的表达,计算增殖指数(PI);TUNEL染色检测肿瘤组织凋亡情况,计算凋亡指数(AI).结果 正常对照组小鼠无肿瘤发生,AOM模型组、5%MS干预组和10% MS干预组小鼠肿瘤发生率分别为86.7%、60.0%、41.7%,组间差异有统计学意义(P =0.048);5%MS干预组平均肿瘤数为1.07±1.10,10% MS干预组为0.67±0.89,均较AOM模型组的2.20±1.21少(P<0.05);10% MS干预组PI为32.0±3.9,均低于AOM模型组和5% MS干预组的59.9±4.4和41.7±4.9(P <0.05);10% MS干预组AI为15.0±2.4,均高于AOM模型组和5% MS干预组的6.9±1.4和9.3±1.5(P<0.05).结论 MS对AOM诱导的小鼠大肠肿瘤具有化学预防作用,其机制为抑制肿瘤细胞增殖和诱导肿瘤细胞凋亡.%Objective To investigate the chemopreventive effects of mustard seed (MS) on azoxymethane (AOM) induced colorectal tumor in mice and to explore its anticancer-related mechanisms. Methods A total of 60 mice of Kunming species were randomly divided into 4 groups of 15 each: AOM alone, AOM + 5% MS, AOM + 10% MS and the control group ( normal saline). Colorectal tumorigenesis was induced by injecting AOM 10 rag/kg, subcutaneously, once a week for three weeks. Different doses of MS were given in diet during the study. Thirty-six weeks later, mice were sacrificed under cervical dislocation. The large intestine was isolated and flushed with ice-cold normal saline. The site, size and number of tumors were recorded. The incidence, the average number anci the inhibitory rate of

  2. Hormonal control of p53 and chemoprevention

    International Nuclear Information System (INIS)

    Improvements in the detection and treatment of breast cancer have dramatically altered its clinical course and outcome. However, prevention of breast cancer remains an elusive goal. Parity, age of menarche, and age at menopause are major risk factors drawing attention to the important role of the endocrine system in determining the risk of breast cancer, while heritable breast cancer susceptibility syndromes have implicated tumor suppressor genes as important targets. Recent work demonstrating hormonal modulation of the p53 tumor suppressor pathway draws together these established determinants of risk to provide a model of developmental susceptibility to breast cancer. In this model, the mammary epithelium is rendered susceptible due to impaired p53 activity during specific periods of mammary gland development, but specific endocrine stimuli serve to activate p53 function and to mitigate this risk. The results focus attention on p53 as a molecular target for therapies to reduce the risk of breast cancer

  3. Chemoprevention of gastric cancer: current status

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    The development of gastric cancer is a multi-factor process. In addition to genetic factors, environmental factors including smoking, low gastric acidity, excessive intake of salt or salty food and low consumption of fresh fruits and vegetables all contribute to the development of gastric cancer. Of particular interest, epidemiological and experimental studies have demonstrated that Helicobacter pylori (H. pylori) infection is causally linked to gastric cancer. Most studies using micronutrient supplementation have failed to demonstrate any preventive effect against the development of gastric cancer. The use of non-steroidal anti-inflammatory drugs has been consistently observed to protect against the development of gastric cancer. Recently, eradication of H. pylori infection by a chemopreventative approach is being studied in a number of trials. Studies using precancerous lesions as an end point of the treatment have produced conflicting and mostly negative results. Trials using cancer as an end point are being cautiously carried out in high-risk populations, and will provide the definitive answer to this important question. In the end, vaccination may be proven to be the optimal strategy in human for the management of H. pylori infection and prevention of gastric cancer.

  4. Cancer chemoprevention and therapy by monoterpenes.

    OpenAIRE

    Gould, M N

    1997-01-01

    Monoterpenes are found in the essential oils of many plants including fruits, vegetables, and herbs. They prevent the carcinogenesis process at both the initiation and promotion/progression stages. In addition, monoterpenes are effective in treating early and advanced cancers. Monoterpenes such as limonene and perillyl alcohol have been shown to prevent mammary, liver, lung, and'other cancers. These compounds have also been used to treat a variety of rodent cancers, including breast and pancr...

  5. Burden and Chemoprevention of Skin Cancer

    NARCIS (Netherlands)

    L.M. Hollestein (Loes)

    2013-01-01

    markdownabstract__Abstract__ The 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 livi

  6. Incorporating Biomarkers in Studies of Chemoprevention.

    Science.gov (United States)

    Fabian, Carol J; Kimler, Bruce F

    2016-01-01

    Despite Food and Drug Administration approval of tamoxifen and raloxifene for breast cancer risk reduction and endorsement by multiple agencies, uptake of these drugs for primary prevention in the United States is only 4% for risk eligible women likely to benefit from their use. Side effects coupled with incomplete efficacy and lack of a survival advantage are the likely reasons. This disappointing uptake, after the considerable effort and expense of large Phase III cancer incidence trials required for approval, suggests that a new paradigm is required. Current prevention research is focused on (1) refining risk prediction, (2) exploring behavioral and natural product interventions, and (3) utilizing novel translational trial designs for efficacy. Risk biomarkers will play a central role in refining risk estimates from traditional models and selecting cohorts for prevention trials. Modifiable risk markers called surrogate endpoint or response biomarkers will continue to be used in Phase I and II prevention trials to determine optimal dose or exposure and likely effectiveness from an intervention. The majority of Phase II trials will continue to assess benign breast tissue for response and mechanism of action biomarkers. Co-trials are those in which human and animal cohorts receive the same effective dose and the same tissue biomarkers are assessed for modulation due to the intervention, but then additional animals are allowed to progress to cancer development. These collaborations linking biomarker modulation and cancer prevention may obviate the need for cancer incidence trials for non-prescription interventions. PMID:26987531

  7. Genetic alterations in carcinogenesis and chemoprevention.

    OpenAIRE

    Rosin, M P

    1993-01-01

    Laboratory and clinical studies suggest that genetic change is intrinsically involved in the development of cancer and that this change occurs in humans throughout carcinogenesis, in both early and late stages. Therefore, the quantification of the level of genetic change in human epithelial tissues may serve as a marker for cancer risk. The micronucleus test has been used to quantify the level of site-specific chromosomal breakage occurring in epithelial tissues of individuals at elevated ris...

  8. What's wrong with chemoprevention of prostate cancer?

    Science.gov (United States)

    Justman, Stewart

    2011-12-01

    When prostate-specific antigen (PSA) testing was introduced, proponents expected it to cut prostate-cancer mortality and did not expect it to unleash an epidemic of unnecessary treatments. Now that evidence of a mortality benefit remains unclear while evidence of overtreatment in undeniable, there is understandable interest in reducing the human costs of the PSA system. Two related drugs, finasteride and dutasteride, both proven to reduce the incidence of prostate cancer and the "risk of diagnosis," are being promoted accordingly. However, if not for the flaws of the PSA system the use of these drugs for purposes of prevention would lose its rationale. Not only are the drugs in this sense dependent on a faulty system, but their own mortality benefits are as speculative as PSA's-in addition to which, they introduce new risks. PMID:22146025

  9. Chemoprevention of Breast Cancer by Dietary Polyphenols

    Directory of Open Access Journals (Sweden)

    Maria-Magdalena Mocanu

    2015-12-01

    Full Text Available 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.

  10. The Chemopreventive Effect of Soybean Isoflavones and Celecoxib on DMBA-induced Breast Cancer in Rats%大豆异黄酮和塞来昔布预防大鼠乳腺癌的发生

    Institute of Scientific and Technical Information of China (English)

    杨定勇; 赵之婧; 覃春阳; 杨立民

    2012-01-01

    Objective To observe the chemopreventive effect of soybean isoflavones and celeeoxib on DMBA-chemically induced breast cancer in rats, and explore the mechanisms. Methods A total of 90 rats were randomly divided into 3 groups: DMBA group (control group) , soybean isoflavones group and celecoxib group, each group contained 30 rats. DMBA was intragastrically given to SD female rats to build breast cancer model. Meanwhile, rats in soybean isoflavones group and celecoxib group received soybean isoflavones and celecoxib treatments, respectively. The occurrence rate, latency period, number of breast cancer were observed and analysed. Results The incidence of mammary tumors in soybean isoflavones group (48.28%) and celecoxib group (48.15%) were both lower than that in the DMBA group (79.31%), with statistical difference (P<0.05). The latency periods of mammary tumors in soybean isoflavones group (14.71 ± 1.90 weeks) and celecoxib group (14.46 ± 1.85 weeks) were longer than that in DMBA group (12.96 ± 2.12 weeks) , with statistical difference (P< 0.05). The tumor numbers of soybean isoflavones group (1.79 + 0.80) and celecoxib group (1.62 ±0.77) were less than that of DMBA group (2.43 ±0.99) , with statistical difference (Ρ<0.05). Conclusion Soybean isoflavones and celecoxib could effectively prevent the occurrence of DMBA-induced breast cancer in female rats.%目的 观察大豆异黄酮和塞来昔布对7,12-二甲基苯蒽(7,12-dimethylhenz anthrancene,DMBA)诱发的大鼠乳腺癌形成的影响,并探讨其抗肿瘤机制.方法 90只SD雌大鼠随机分成DMBA组(A组)、DMBA+SOY(B组)组和DMBA+塞来昔布(C组)3组,每组30只.分别给予DMBA油剂灌胃复制大鼠乳腺癌模型,同时B组和C组分别给予含SOY及塞来昔布的饲料喂养至实验结束,观察各组大鼠乳腺癌的发生率、潜伏期及肿瘤数目.结果 B组(48.28%)和C组(48.15%)乳腺癌发生率低于A组(79.31%),差异有统计学意义(P<0.05);B组(14.71±1.90)

  11. Evaluation of chemopreventive response of two cycloxygenase-2 inhibitors, etoricoxib and diclofenac in rat colon cancer using FTIR and NMR spectroscopic techniques Evaluación de la respuesta quimiopreventiva de dos inhibidores de la ciclooxigenasa 2, etoricoxib y diclofenaco en el cáncer de colon murino empleando las técnicas espectroscópicas FTIR Y NMR

    Directory of Open Access Journals (Sweden)

    M. Kaur Saini

    2010-08-01

    Full Text Available Non steroidal anti inflammatory drugs (NSAIDs are efficacious in chemoprevention of colorectal cancer. Therefore, the potential ability of Etoricoxib, a selective cycloxygenase-2(COX-2 inhibitor and Diclofenac, a preferential COX-2 inhibitor are considered in the chemoprevention of 1, 2-dimethylhydrazine (DMH induced colon carcinogenesis in rat model. DMH was injected s.c. for six weeks while Etoricoxib and Diclofenac were fed daily orally alone and also in combination with an weekly subcutaneous injection of 1,2-dimethylhydrazine dihydrochloride (DMH to the rats. After the treatment period of 6 weeks the animals were sacrificed by an overdose of ether anesthesia and the colonic tissues were removed and studied by the FTIR and NMR Spectroscopic techniques to evaluate the changes occurring in the lipid bilayer of colonic membrane lipids. The alterations in wave number of FTIR spectra as well as the chemical shifts of NMR spectra were recorded which signify the modulation of membrane lipids during colon carcinogenesis and possible cancer prevention by the oral administration of NSAIDs in an experimental model of chemical induced colon carcinogenesis.Los fármacos antiinflamatorios no esteroideos (AINE son eficaces en la prevención del cáncer colorrectal. Por lo tanto, la capacidad potencial de Etoricoxib, un inhibidor selectivo de la ciclooxigenasa-2(COX-2, y de Diclofenaco, un inhibidor preferencial de la COX-2, se considera en la quimioprevención de la carcinogénesis de colon inducida por 1, 2-dimetilhidracina (DMH en el modelo murino. Se inyectó s.c. DMH durante 6 semanas a la vez que se administraban diariamente por vía oral Etoricoxib y Diclofenaco solos y en combinación con una inyección s.c. semanal de dihidrocloruro de 1,2-dimetilhidracina (DMH a las ratas. Después del período de tratamiento de 6 semanas, se sacrificó a los animales mediante una sobredosis de anestesia con éter y se extirpó el tejido colónico para estudio con

  12. Rice bran phytochemicals and dietary colon chemoprevention teamwork

    Science.gov (United States)

    A growing body of evidence supports that dietary rice bran exhibits gastrointestinal cancer control and prevention activity using carcinogen induced animal models and human colon cancer cell lines. Our laboratory has recently reported metabolomic differences in rice from globally and genetically dis...

  13. Antioxidative and Chemopreventive Properties of Vernonia amygdalina and Garcinia biflavonoid

    OpenAIRE

    Olatunde Owoeye; Farombi, Ebenezer O.

    2011-01-01

    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, cou...

  14. Targeting Hyaluronic Acid Family for Cancer Chemoprevention and Therapy

    OpenAIRE

    Lokeshwar, Vinata B.; Mirza, Summan; Jordan, Andre

    2014-01-01

    Hyaluronic acid or hyaluronan (HA) is perhaps one of the most uncomplicated large polymers that regulates several normal physiological processes and, at the same time, contributes to the manifestation of a variety of chronic and acute diseases, including cancer. Members of the HA signaling pathway (HA synthases, HA receptors, and HYAL-1 hyaluronidase) have been experimentally shown to promote tumor growth, metastasis, and angiogenesis, and hence each of them is a potential target for cancer t...

  15. Cancer Chemoprevention by Pomegranate: Laboratory and Clinical Evidence

    OpenAIRE

    Adhami, Vaqar Mustafa; Khan, Naghma; Mukhtar, Hasan

    2009-01-01

    Pomegranate fruit from the tree Punica granatum has been dubbed as the “nature’s power fruit.” Dating back to Biblical times, the tree itself is attributed to possess extraordinary medicinal properties. The geographical distribution of the tree, being native to the Middle East and some Asian countries, is generally attributed to a lack of interest in its medicinal properties by many western scientists. However, the unique biochemical composition of the pomegranate fruit being rich in antioxid...

  16. Treatment and chemoprevention of NSAID-associated gastrointestinal complications

    Directory of Open Access Journals (Sweden)

    Edward J Frech

    2008-12-01

    Full Text Available Edward J Frech1,2, Mae F Go1,21GI Section, George E Wahlen Department of Veterans Affairs Medical Center; 2Division of Gastroenterology, University of Utah School of Medicine, Salt Lake City, Utah, USAAbstract: The use of non-steroidal anti-inflammatory drugs has become ubiquitous worldwide and remains a common source of gastrointestinal morbidity. Antisecretory medications, particularly proton pump inhibitors, are effective in the treatment and prevention of NSAID-related gastrointestinal complications, including peptic ulcer disease and non-ulcer dyspepsia. A careful assessment of patients’ risk factors for developing NSAID-related gastrointestinal complications should be undertaken prior to initiation of any NSAIDs. Patients who are considered at risk for developing gastrointestinal complications should receive concurrent antisecretory medical therapy to minimize the risk for GI complications.Keywords: NSAIDs, peptic ulcer disease, gastrointestinal prophylaxis

  17. Highly Loaded, Sustained-Release Microparticles of Curcumin for Chemoprevention

    OpenAIRE

    Shahani, Komal; Panyam, Jayanth

    2011-01-01

    Curcumin, a dietary polyphenol, has preventive and therapeutic potential against several diseases. Because of the chronic nature of many of these diseases, sustained-release dosage forms of curcumin could be of significant clinical value. However, extreme lipophilicity and instability of curcumin are significant challenges in its formulation development. The objectives of this study were to fabricate an injectable microparticle formulation that can sustain curcumin release over a 1-month peri...

  18. 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.

  19. Nanoencapsulation of pomegranate bioactive compounds for breast cancer chemoprevention

    OpenAIRE

    Shirode AB; Bharali DJ; Nallanthighal S; Coon JK; Mousa SA; Reliene R

    2015-01-01

    Amit B Shirode,1,2,* Dhruba J Bharali,3,* Sameera Nallanthighal,1,2 Justin K Coon,1,2 Shaker A Mousa,3 Ramune Reliene1,2 1Department of Environmental Health Sciences, University at Albany, State University of New York, Albany, NY, USA; 2Cancer Research Center, University at Albany, Rensselaer, NY, USA; 3Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY, USA *These authors contributed equally to this work Abstract: Pomegranate polyphenols are...

  20. Novel Investigations of Flavonoids as Chemopreventive Agents for Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Chen-Yi Liao

    2015-01-01

    Full Text Available We would like to highlight the application of natural products to hepatocellular carcinoma (HCC. We will focus on the natural products known as flavonoids, which target this disease at different stages of hepatocarcinogenesis. In spite of the use of chemotherapy and radiotherapy in treating HCC, patients with HCC still face poor prognosis because of the nature of multidrug resistance and toxicity derived from chemotherapy and radiotherapy. Flavonoids can be found in many vegetables, fruits, and herbal medicines that exert their different anticancer effects via different intracellular signaling pathways and serve as antioxidants. In this review, we will discuss seven common flavonoids that exert different biological effects against HCC via different pathways.

  1. Novel Investigations of Flavonoids as Chemopreventive Agents for Hepatocellular Carcinoma

    OpenAIRE

    Chen-Yi Liao; Ching-Chang Lee; Chi-chang Tsai; Chao-Wen Hsueh; Chih-Chiang Wang; I-Hung Chen; Ming-Kai Tsai; Mei-Yu Liu; An-Tie Hsieh; Kuan-Jen Su; Hau-Ming Wu; Shih-Chung Huang; Yi-Chen Wang; Chien-Yao Wang; Shu-Fang Huang

    2015-01-01

    We would like to highlight the application of natural products to hepatocellular carcinoma (HCC). We will focus on the natural products known as flavonoids, which target this disease at different stages of hepatocarcinogenesis. In spite of the use of chemotherapy and radiotherapy in treating HCC, patients with HCC still face poor prognosis because of the nature of multidrug resistance and toxicity derived from chemotherapy and radiotherapy. Flavonoids can be found in many vegetables, fruits, ...

  2. Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer

    OpenAIRE

    Malik, Arshi; Afaq, Farrukh; Sarfaraz, Sami; Adhami, Vaqar M.; Syed, Deeba N.; Mukhtar, Hasan

    2005-01-01

    Prostate cancer is the most common invasive malignancy and the second leading cause of cancer-related deaths among U.S. males, with a similar trend in many Western countries. One approach to control this malignancy is its prevention through the use of agents present in diet consumed by humans. Pomegranate from the tree Punica granatum possesses strong antioxidant and antiinflammatory properties. We recently showed that pomegranate fruit extract (PFE) possesses remarkable antitumor-promoting e...

  3. 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

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

    OpenAIRE

    Chong-Zhi Wang; Yi Cai; Samantha Anderson; Chun-Su Yuan

    2015-01-01

    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 ent...

  5. 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. |

  6. Pharmacokinetic and Chemoprevention Studies on Tea in Humans

    OpenAIRE

    Chow, H-H. Sherry; Hakim, Iman A.

    2011-01-01

    Green tea and its major polyphenols constituents, tea catechins, have been shown to have many health benefits including cancer prevention. Tea catechins and tea catechin metabolites/catabolites are bioavailable in the systemic circulation after oral intake of green tea or green tea catechins. The metabolites/catabolites identified in humans include glucuronide/sulfate conjugates, methylated tea catechin conjugates, and microflora-mediated ring fission products and phenolic acid catabolites. P...

  7. Phase 0 Trials: Expediting the Development of Chemoprevention Agents

    OpenAIRE

    Kummar, Shivaani; Doroshow, James H.

    2011-01-01

    Phase 0 trials are first-in-human clinical trials performed under the Exploratory IND [investigational new drug] Guidance of the US Food and Drug Administration. Unlike traditional phase I trials, these studies have no therapeutic or diagnostic intent but instead aim to provide only pharmacokinetic and/or pharmacodynamic data to inform the next step in developing an agent. We discuss the role that such trials, including one reported by Reid et al. (beginning on page XXX in this issue of the j...

  8. Oral Carcinogenesis and Oral Cancer Chemoprevention: A Review

    OpenAIRE

    Takahiro Tanaka; Mayu Tanaka; Takuji Tanaka

    2011-01-01

    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 adv...

  9. Pancreatic Cancer Chemoprevention Translational Workshop | Division of Cancer Prevention

    Science.gov (United States)

    Thursday, September 10th (6:00 to 9:30 PM) Welcome Barnett Kramer, MD, MPH (6:00 to 6:10 PM) Director of the Division of Cancer Prevention, NCI Introduction – Goals of the Workshop: ABCs of Cancer Prevention (Agents, Biomarkers, Cohorts) Mark Miller, PhD (6:10 to 6:25 PM) Program Director Division of Cancer Prevention, NCI |

  10. Altered membrane lipid dynamics and chemoprevention by non-steroidal anti inflammatory drugs during colon carcinogenesis Alteración de la dinámica de los lípidos de membrana y quimioprevención mediante los fármacos antiinflamatorios no esteroideos en la carcinogénesis de colon

    Directory of Open Access Journals (Sweden)

    S. Singh Kanwar

    2011-10-01

    Full Text Available The present work focuses on the anti-neoplastic role of non steroidal anti-inflammatory drugs (NSAIDs in modulating the biophysical parameters of the colonic membranes in 1,2-dimethylhydrazine dihydrochloride (DMH induced carcinogenesis. The steady-state fluorescence polarization technique was applied to assess membrane fluidity, membrane polarity and lipid phase states. The decline in cholesterol content, biosynthesis and cholesterol: phospholipids ratio with DMH treatment indicates more fluidity associated with carcinogenesis. The DMH group had shown lower order parameter indicating more fluidity whereas NSAIDs resulted in increasing the membrane lipid order. The converging effects of these changes were more in membrane phase separations and membrane phase state. In DMH treatment membrane shows lesser phase separation or high polarity, and more liquid crystalline state while for NSAID groups membranes have higher phase separations or low polarity, and more of the gel phase. Further, NSAIDs induced anti-proliferative effects were evidently observed by apoptosis in the colonocytes by using acridine orange-ethidium bromide fluorescent staining and Terminal de-oxynucleotidyl transferase dUTP nick end labeling (TUNEL assay. The results suggest that NSAIDs induced alteration in the membrane biophysical parameters may be an important initiating event for the chemopreventive action.Este trabajo se centra en el papel antineoplásico de los fármacos antiinflamatorios no esteroideos (AINE en la modulación de los parámetros biofísicos de las membranas colónicas en la carcinogénesis inducida por 1,2-dihidrocloruro de dimetilhidracina (DMH. Se aplicó la técnica de polarización de la fluorescencia en estado de equilibrio para evaluar la fluidez de la membrana, su polaridad y los estados de fase lipídica. El declive del contenido de colesterol, la biosíntesis y el cociente colesterol: fosfolípidos con el tratamiento con DMH indica más fluidez

  11. Women victims of sexual violence: adherence to chemoprevention of HIV Mujeres víctimas de la violência sexual: adhesión a la quimioprofilaxia del HIV Mulheres vítimas de violência sexual: adesão à quimioprofilaxia do HIV

    Directory of Open Access Journals (Sweden)

    Normélia Maria Freire Diniz

    2007-02-01

    Full Text Available This study aimed to investigate the adherence of women victims of sexual violence, to AIDS chemoprevention treatment. A quantitative study was carried out at a care service to victims of sexual violence in Salvador (Bahia, Brazil. Study participants were 172 women. Data were collected through interviews with forms and consultation of patient files. The results showed that 45.4% of the abused women were teenagers and 40.7% of the attended women were raped. Only 54% of the women were advised to use antiretrovirals to prevent HIV. Adherence to treatment occurred in 57.4% of cases and discontinuity corresponded to 42.6%. Non-adherence to treatment was attributed to psychological or emotional disorders and non-understanding of the established treatment. Therefore, it is important that professionals pay careful attention in order to perceive the conditions that might increase women's vulnerability to the infection.La finalidad de este estudio fue investigar si las mujeres víctimas de violencia sexual adhieren o no al uso de medicamentos para prevención del HIV. Fue realizado un estudio cuantitativo en un servicio de atención a personas sexualmente violentadas, ubicado en Salvador (Bahía, Brasil. Participaron del estudio 172 mujeres. Los datos fueron recopilados a través de entrevistas dirigidas y consulta a los archivos. Los resultados demostraron que el 45.4% de las mujeres víctimas de violencia eran adolescentes y que el 40.7% de las mujeres asistidas fueron violadas. Sólo el 54% de las mujeres fue aconsejado a usar medicamentos antiretrovirales para prevención del VIH, El 57.4% de ellas adhirió al tratamiento y el 42.6% no lo continuó. Aquellas que no adhirieron al tratamiento alegaron disturbios psicológico y/o emocional o no comprensión del tratamiento instituido. Por lo tanto, es necesaria una mirada atenta de los profesionales para percibir las condiciones que implican un aumento en la vulnerabilidad de las mujeres a la infecci

  12. El té verde en la quimioprevención in vivo del daño genotóxico inducido por metales cancerígenos (cromo [VI] Green tea and its role on chemoprevention in vivo of genotoxic damage induced by carcinogenic metals (Chromium [VI

    Directory of Open Access Journals (Sweden)

    M. C. García-Rodríguez

    2012-08-01

    treatment with chromium trioxide, (iv treatment with green tea and chromium trioxide. The green tea was administrated via intragastric tube every 12 hours over two days (4 doses of 0.25 ml infusions 1.6 g/7.5 ml and ad libitum (5.6 ml/day for 10 days infusions of 3.2 g/100 ml, while chromium trioxide was administrated via intraperitoneal (20 mg/kg. Blood samples were obtained from the caudal vein, the number of MN in EPC was assessed at 0, 24, 48 and 72 hours after the treatments. Results: The group treated with green tea showed no significant statistical changes in the average of MN. On the other hand, the group that was dosed with the chromium trioxide showed an increase between 4 and 8 MN, which was statistically significant when compared with control group, which confirmed the genotoxic damage. When the green tea treatment was administered before the application of chromium trioxide, there was a decrease in MN frequencies of 31 and 62% at 72 hours, 20 and 35% at 48 hours and 18 and 31% at 24 hours with intragastric and ad libitum respectively, compared with the group treated only with chromium trioxide. Hence, green tea reduced the genotoxic damage induced by chromium trioxide, and the highest protection was presented at 72 hours. Conclusions: Our findings support the protective effects of green tea against the damage of genetic material, induced by metal compounds such as chromium [VI], suggesting that its antioxidant compounds are those that have a chemopreventive effect on the EOX generated by the Cr [VI] during its reduction to Cr (III. The fact that the largest decrease in the frequency of MN was observed at 72 hours and ad libitum treatment, suggests that, the protective effect depends on the bioavailability, pharmacodynamics and pharmacokinetics of the active ingredient in green tea, so the administration of green tea for a long period of time before the exposure to Cr [VI] could have a more consistent preventive effect.

  13. Chemoprevention of Barley and Sage against acrylamide-Induced genotoxic, biochemical and histopathological alterations in rats

    Directory of Open Access Journals (Sweden)

    Sekena, H. Abd El-Aziem1, Mosaad A. Abdel-Wahab2, Mahmoud A. M3Azza M

    2004-06-01

    Full Text Available Acrylamide (ACR has recently been found in fried and backed foods, suggesting widespread public exposure. ACR is an industrial chemical material that causes neurotoxicity in humans and was designated as a probable human carcinogen by IARC and USEPA. The aim of the present study was to evaluate the protective effects of barley and sage against ACR mutagenicity and biochemical and histopathological changes in rats. Forty mature male rats were divided into eight groups and were fed barley and/or sage-supplemented diet (5% with or without ACR (50 mg/kg b.w. The biochemical results revealed that ACR increased Alanine amino transferase (ALT, Aspartate amino transferase (AST, triglycerides (TG, cholesterol and uric acid. Micronucleated polychromatic erythrocytes and chromosomal aberrations in somatic and germ cells were significantly increased in ACR-treated animals. Severe pathological lesions included testicular degeneration, oedema, spermatid giant cells formation and necrosis of spermatid cells were found in the testis of ACR-treated group. The kidney of this group showed degenerative changes. Cotreatment with barley and/or Sage and ACR resulted in a significant improvement in all the parameters tested. It could be concluded that these plants contain antioxidant compounds and may be useful when add as food additive to the food cooked on a higher temperature.

  14. COX-Independent Mechanisms of Cancer Chemoprevention by Anti-Inflammatory Drugs

    OpenAIRE

    Gurpinar, Evrim; Grizzle, William E.; Piazza, Gary A.

    2013-01-01

    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...

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

    OpenAIRE

    Evrim eGurpinar; Grizzle, William E.; Piazza, Gary A.

    2013-01-01

    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...

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Chemoprevention of DMBA-induced mammary carcinogenesis in rats by low-dose EPA and DHA.

    OpenAIRE

    Noguchi, M.; Minami, M; Yagasaki, R.; Kinoshita, K; Earashi, M.; Kitagawa, H; Taniya, T.; Miyazaki, I.

    1997-01-01

    We investigated the effects of low-dose eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the incidence and growth of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in rats fed a high-fat (HF) diet. We also examined the effects of these treatments on the fatty acid composition of tumour and serum. Tumour incidence was significantly decreased by the administration of low-dose EPA and DHA, whereas their inhibitory effects on tumour growth did not reach significance....

  18. Novel Marine Phenazines as Potential Cancer Chemopreventive and Anti-Inflammatory Agents

    OpenAIRE

    Rui Yu; van Breemen, Richard B.; Asolkar, Ratnakar N.; Murphy, Brian T.; William Fenical; Kondratyuk, Tamara P.; Pezzuto, John M.; Eun-Jung Park

    2012-01-01

    Two new (1 and 2) and one known phenazine derivative (lavanducyanin, 3) were isolated and identified from the fermentation broth of a marine-derived Streptomyces sp. (strain CNS284). In mammalian cell culture studies, compounds 1, 2 and 3 inhibited TNF-α-induced NFκB activity (IC50 values of 4.1, 24.2, and 16.3 μM, respectively) and LPS-induced nitric oxide production (IC50 values of >48.6, 15.1, and 8.0 μM, respectively). PGE2 production was blocked with greater efficacy (IC50 values of 7...

  19. Light-Induced Toxic Effects of Tamoxifen: A Chemotherapeutic and Chemopreventive Agent

    OpenAIRE

    Wang, Lei; Wang, Shuguang; Yin, Jun-Jie; Peter P. Fu; Yu, Hongtao

    2009-01-01

    Tamoxifen is a powerful drug used to treat breast cancer patients, and more than 500,000 women in the U. S. are being treated with this drug. In our study, tamoxifen is found to be photomutagenic in Salmonella typhimurium TA102 at concentrations as low as 0.08 μM and reaches maximum photomutagenicity at 0.4 μM under a light dose equivalent to 20 min sunlight. These concentrations are comparable to the plasma tamoxifen concentration of 0.4 to 3 μM for patients undergoing tamoxifen therapy. The...

  20. Chemopreventive effect of cactus Opuntia ficus indica on oxidative stress and genotoxicity of aflatoxin B1

    Directory of Open Access Journals (Sweden)

    Ben Mansour Hédi

    2011-10-01

    Full Text Available Abstract Background Aflatoxin B1 (AFB1 is potent hepatotoxic and hepatocarcinogenic agent. In aflatoxicosis, oxidative stress is a common mechanism contributing to initiation and progression of hepatic damage. The aim of this work was to evaluate the hepatoprotective effect of cactus cladode extract (CCE on aflatoxin B1-induced liver damage in mice by measuring malondialdehyde (MDA level, the protein carbonyls generation and the heat shock proteins Hsp 70 and Hsp 27 expressions in liver. We also looked for an eventual protective effect against AFB1-induced genotoxicity as determined by chromosome aberrations test, SOS Chromotest and DNA fragmentation assay. We further evaluated the modulation of p53, bax and bcl2 protein expressions in liver. Methods Adult, healthy balbC (20-25 g male mice were pre-treated by intraperitonial administration of CCE (50 mg/Kg.b.w for 2 weeks. Control animals were treated 3 days a week for 4 weeks by intraperitonial administration of 250 μg/Kg.b.w AFB1. Animals treated by AFB1 and CCE were divided into two groups: the first group was administrated CCE 2 hours before each treatment with AFB1 3 days a week for 4 weeks. The second group was administrated without pre-treatment with CCE but this extract was administrated 24 hours after each treatment with AFB1 3 days a week for 4 weeks. Results Our results clearly showed that AFB1 induced significant alterations in oxidative stress markers. In addition, it has a genotoxic potential and it increased the expression of pro apoptotic proteins p53 and bax and decreased the expression of bcl2. The treatment of CCE before or after treatment with AFB1, showed (i a total reduction of AFB1 induced oxidative damage markers, (ii an anti-genotoxic effect resulting in an efficient prevention of chromosomal aberrations and DNA fragmentation compared to the group treated with AFB1 alone (iii restriction of the effect of AFB1 by differential modulation of the expression of p53 which decreased as well as its associated genes such as bax and bcl2. Conclusion We concluded that CCE might have a hepatoprotective effect against aflatoxicosis in mice, probably acting by promoting the antioxidant defence systems.

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

    OpenAIRE

    Mayu Tanaka; Toshiya Kuno; Takahiro Tanaka; Takuji Tanaka

    2011-01-01

    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 ...

  2. Chemopreventive Effect of PSP Through Targeting of Prostate Cancer Stem Cell-Like Population

    OpenAIRE

    Luk, Sze-Ue; Lee, Terence Kin-Wah; Liu, Ji; Lee, Davy Tak-Wing; Chiu, Yung-Tuen; Ma, Stephanie; Ng, Irene Oi-Lin; Wong, Yong-Chuan; Chan, Franky Leung; Ling, Ming-Tat

    2011-01-01

    Recent evidence suggested that prostate cancer stem/progenitor cells (CSC) are responsible for cancer initiation as well as disease progression. Unfortunately, conventional therapies are only effective in targeting the more differentiated cancer cells and spare the CSCs. Here, we report that PSP, an active component extracted from the mushroom Turkey tail (also known as Coriolus versicolor), is effective in targeting prostate CSCs. We found that treatment of the prostate cancer cell line PC-3...

  3. Chemoprevention of aberrant crypt foci in the colon of rats by dietary onion.

    OpenAIRE

    Taché, Sylviane; Ladam, Aélis; Corpet, Denis E

    2007-01-01

    International audience Onion intake might reduce the risk of colorectal cancer, according to epidemiology. However, Femia showed in 2003 that diets with a 20% onion intake increase carcinogenesis in rats. We speculated this dose was too high. Prevention of initiation was thus tested in 60 rats given a 5% dried onion diet or AIN76 diet, and initiated 12 days later with azoxymethane (AOM, 1x20 mg/kg i.p.), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ, 2x200 mg/kg p.o.), or N-nitroso-N-methylu...

  4. Women's experiences and views about costs of seeking malaria chemoprevention and other antenatal services

    DEFF Research Database (Denmark)

    Mubyazi, Godfrey M.; Bloch, Paul; Magnussen, Pascal;

    2010-01-01

    the health seeking behaviour of pregnant women because it seriously affected their domestic responsibilities. CONCLUSION: A variety of resource-related factors were shown to affect the health seeking behaviour of pregnant women in rural Tanzania. Thus, accessibility to ANC services was hampered by...

  5. A Search for the Optimum Selenium Source to Obtain Mushroom-Derived Chemopreventive Preparations.

    Science.gov (United States)

    Savic, Milena; Klimaszewska, Marzenna; Bamburowicz-Klimkowska, Magdalena; Suchocki, Piotr; Niksic, Miomir; Szutowski, Miroslaw; Wroczynski, Piotr; Turlo, Jadwiga

    2016-01-01

    The objective of this research was to test whether selenium-yeast (Se-yeast) is a better source of selenium than sodium selenite for accumulation in mycelia and immunoactive cell wall polysaccharides. Culture media were enriched in selenium to a concentration of 20 µg/mL. Selenium was added to the medium either in the form of sodium selenite or in form of Se-yeast (Sel-Plex; Alltech Inc., Lexington, KY). The total selenium concentrations in the mycelium biomass and in the isolated crude polysaccharides were determined using atomic absorption spectroscopy. We found that selenium accumulated more efficiently in cultures enriched with Se-yeast. A higher concentration of selenium was also found in the crude polysaccharide fractions isolated from the mycelium grown in Se-yeast-enriched media. With the use of the needle trap gas chromatography-mass spectrometry method, we found that there are significant differences in the composition of the volatile aroma and flavor compounds secreted by the mycelia cultivated in different media. PMID:27481294

  6. The Immunomodulation and Anti-Inflammatory Effects of Garlic Organosulfur Compounds in Cancer Chemoprevention

    OpenAIRE

    Schäfer, Georgia; Kaschula, Catherine H.

    2014-01-01

    Garlic (Allium sativum) has been used for centuries as a prophylactic and therapeutic medicinal agent. Importantly, garlic has been suggested to have both cancer-preventive potential as well as significant enhancing effects on the immune system. While these observations are supported experimentally both in vitro and in vivo, the impact of garlic in assisting the immune system in the prevention of cancer still lacks experimental confirmation. Studies addressing the immunomodulatory effects of ...

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Stage matters: choosing relevant model systems to address hypotheses in diet and cancer chemoprevention research.

    OpenAIRE

    Fenton, Jenifer I.; Hord, Norman G.

    2006-01-01

    KEYWORDS - CLASSIFICATION: Adult;Animals;Anticarcinogenic Agents;Cell Line;Cell Line,Tumor;Colon;diet therapy;Diet;Disease Models,Animal;Disease Progression;Epithelium;Genome;Humans;mechanisms of carcinogenesis;Mice;Mice,Inbred C57BL;Neoplasms;prevention & control;Research;Risk;therapeutic use;utilization.

  9. Chemopreventive potential of an Indian medicinal plant (Tinospora cordifolia) on skin carcinogenesis in mice.

    Science.gov (United States)

    Chaudhary, Ranu; Jahan, Swafiya; Goyal, P K

    2008-01-01

    Tinospora cordifolia (Guduchi), an Indian medicinal plant, was used to explore antitumor promoting activity in a two-stage skin carcinogenesis model. For this purpose, mice were treated by single application of DMBA (100 microg/100 microl of acetone) and two weeks later promoted by croton oil (1% in acetone three times a week) until the end of the experiment (i.e., 16 weeks). Oral administration of the above extract at the preinitiational stage (i.e., seven days before and seven days after DMBA application; group IV), promotional stage (i.e., from the time of croton oil application; group V), and both pre- and postintiational stage (i.e., from the time of DMBA application and continued until the end of the experiment; group VI; on the shaven backs of the mice at the dose of 100 mg/kg body weight/day for 16 weeks) recorded significant reduction in tumor weight, tumor incidence in comparison to control (i.e., mice treated with DMBA and croton oil; group III). Furthermore, cumulative number of papillomas, tumor yield, tumor burden, and tumor weight showed significant reduction along with significant elevation of phase II detoxifying enzymes, and inhibition of lipid peroxidation in liver and skin in the animals administered with such plant extract concomitant to carcinogen exposure. Thus, the present data strongly suggests that the Tinospora cordifolia extract has anti-tumor potential in a two-stage skin carcinogenesis mouse model. PMID:18652570

  10. Phenolic profiles and antioxidant and anticarcinogenic activities of Greek herbal infusions; balancing delight and chemoprevention?

    Science.gov (United States)

    Kaliora, Andriana C; Kogiannou, Dimitra A A; Kefalas, Panagiotis; Papassideri, Issidora S; Kalogeropoulos, Nick

    2014-01-01

    Total phenolic content, antioxidant activity and phenolic profiles of six herbal infusions - namely rosemary, Cretan dittany, St. John's Wort, sage, marjoram and thyme were assayed. Additionally, the infusion anticarcinogenic effect as to their ability to (a) scavenge free radicals, (b) inhibit cell growth, (c) decrease IL-8 levels and (d) regulate p65 subunit in epithelial colon cancer (HT29) and prostate (PC3) cancer cells was investigated. LC-DAD-MS and GC-MS analyses showed major qualitative and quantitative differences in phenolic profiles of the infusions. All herbal infusions exhibited antiradical activity which correlated strongly with their total phenolic content. Infusions exhibited the potential to inhibit cell growth and to reduce IL-8 levels in HT29 colon and PC3 prostate cancer cells. The regulation reported in p65 subunit in HT29 treated with St John's Wort and in PC3 treated with thyme might point to the NF-κB as the molecular target underlying the effect of these infusions. PMID:24001836

  11. 15-Hydroxyprostaglandin dehydrogenase inactivation as a mechanism of resistance to celecoxib chemoprevention of colon tumors.

    LENUS (Irish Health Repository)

    Yan, Min

    2009-06-09

    Pharmacologic inhibitors of the prostaglandin-synthesizing COX-2 oncogene prevent the development of premalignant human colon adenomas. However, resistance to treatment is common. In this study, we show that the adenoma prevention activity of the COX-2 inhibitor celecoxib requires the concomitant presence of the 15-hydroxyprostaglandin dehydrogenase (15-PGDH) tumor suppressor gene, and that loss of 15-PGDH expression imparts resistance to celecoxib\\'s anti-tumor effects. We first demonstrate that the adenoma-preventive activity of celecoxib is abrogated in mice genetically lacking 15-PGDH. In FVB mice, celecoxib prevents 85% of azoxymethane-induced tumors >1 mm in size, but is essentially inactive in preventing tumor induction in 15-PGDH-null animals. Indeed, celecoxib treated 15-PGDH null animals develop more tumors than do celecoxib naive WT mice. In parallel with the loss of tumor prevention activity, celecoxib-mediated suppression of colonic PGE(2) levels is also markedly attenuated in 15-PGDH-null versus WT mice. Finally, as predicted by the murine models, humans with low colonic 15-PGDH levels also exhibit celecoxib resistance. Specifically, in a colon adenoma prevention trial, in all cases tested, individuals who developed new adenomas while receiving celecoxib treatment were also found as having low colonic 15-PGDH levels.

  12. Chemopreventive effect of zingerone against colon carcinogenesis induced by 1,2-dimethylhydrazine in rats.

    Science.gov (United States)

    Vinothkumar, Rajenderan; Vinothkumar, Rajamanickam; Sudha, Mani; Nalini, Namasivayam

    2014-09-01

    Zingerone [4-(4-hydroxy-3-methoxyphenyl)-2-butane], one of the active phenolic components isolated from Zingiber officinale, has antioxidant and anticarcinogenic properties. In our study, we have evaluated the effect of different doses of zingerone on lipid peroxidation (thiobarbituric acid-reactive substances, lipid hydroxyl radical and conjugated dienes), tissue enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase), and nonenzymatic antioxidants (reduced glutathione, vitamin E, vitamin C), and also the formation of aberrant crypt foci (ACF) in male albino Wistar rats with colon cancer induced using 1,2-dimethylhydrazine (DMH). The rats were divided into six groups. Group 1 served as a control group and received a modified pellet diet; the rats in group 2 received a modified pellet diet along with zingerone (40 mg/kg b.w., orally every day); groups 3-6 were administered DMH (20 mg/kg b.w., subcutaneously) once a week for the first 4 weeks; and groups 4-6 received zingerone at three different doses of 10, 20 and 40 mg/kg b.w., respectively, every day for 16 weeks. Increased tumour incidence and ACF formation were accompanied by a decrease in the tissue lipid peroxidation, enzymatic and nonenzymatic antioxidant activities observed in the colon of DMH-treated rats. Supplementation with zingerone in DMH-treated rats led to a significant decrease in the tumour incidence and ACF formation with simultaneous modulation in the level of tissue lipid peroxidation and antioxidant status. Thus, in conclusion, we can suggest that zingerone effectively inhibits DMH-induced colon carcinogenesis in male Wistar rats. PMID:23903760

  13. Network-Based Analysis of Nutraceuticals in Human Hepatocellular Carcinomas Reveals Mechanisms of Chemopreventive Action

    OpenAIRE

    Michailidou, M.; Melas, I.; Messinis, D.; Klamt, S; Alexopoulos, L; F. Kolisis; Loutrari, H

    2015-01-01

    Chronic inflammation is associated with the development of human hepatocellular carcinoma (HCC), an essentially incurable cancer. Anti-inflammatory nutraceuticals have emerged as promising candidates against HCC, yet the mechanisms through which they influence the cell signaling machinery to impose phenotypic changes remain unresolved. Herein we implemented a systems biology approach in HCC cells, based on the integration of cytokine release and phospoproteomic data from high-throughput xMAP ...

  14. Osteopontin is a potential target gene in mouse mammary cancer chemoprevention by Se-methylselenocysteine

    International Nuclear Information System (INIS)

    Se-methylselenocysteine (MSC) is a naturally occurring organoselenium compound that inhibits mammary tumorigenesis in laboratory animals and in cell culture models. Previously we have documented that MSC inhibits DNA synthesis, total protein kinase C and cyclin-dependent kinase 2 kinase activities, leading to prolonged S-phase arrest and elevation of growth-arrested DNA damage genes, followed by caspase activation and apoptosis in a synchronized TM6 mouse mammary tumor model. The aim of the present study was to examine the efficacy of MSC against TM6 mouse mammary hyperplastic outgrowth (TM6-HOG) and to determine in vivo targets of MSC in this model system. Twenty mammary fat pads each from female Balb/c mice transplanted with TM6-HOG and fed with 0.1 ppm selenium and with 3 ppm selenium respectively, were evaluated at 4 and 12 weeks after transplantation for growth spread, proliferative index and caspase-3 activity. Thirteen mice transplanted with TM6-HOG in each selenium group were observed for tumor formation over 23 weeks. Tumors from mice in both groups were compared by cDNA array analysis and data were confirmed by reverse transcription–polymerase chain reaction. To determine the effect of MSC on the expression of the novel target gene and on cell migration, experiments were performed in triplicate. A dietary dose of 3 ppm selenium significantly reduced the growth spread and induced caspase-3 activity in mammary fat pads in comparison with mice fed with the basal diet (0.1 ppm selenium). The extended administration (23 weeks) of 3 ppm selenium in the diet resulted in a tumor incidence of 77% in comparison with 100% tumor incidence in 0.1 ppm selenium-fed animals. The size of TM6 tumors in the supplemented group was smaller (mean 0.69 cm2) than in the mice fed with the basal diet (mean 0.93 cm2). cDNA array analysis showed a reduced expression of osteopontin (OPN) in mammary tumors of mice fed with the 3 ppm selenium diet in comparison with OPN expression in tumors arising in 0.1 ppm selenium-fed mice. A 24-hour treatment of TM6 cells with MSC significantly inhibited their migration and also reduced their OPN expression in comparison with untreated cells. OPN is a potential target gene in the inhibition of mammary tumorigenesis by selenium

  15. Non-Edible Plants as an Attractive Source of Compounds with Chemopreventive Potential

    OpenAIRE

    Ji, Seungwon; Orlikova, Barbora; Diederich, Marc

    2014-01-01

    Cancer remains a lethal disease, and many scientists are currently trying to develop more effective therapies. Natural compounds are potential sources of anti-cancer therapies and are obtained from diverse sources including marine organisms, microorganisms and plants. In this paper, we evaluated natural compounds from non-edible plant sources, which is a neglected area of research despite the promising future of these compounds. In addition, we assessed the function and mechanism of action of...

  16. UV-induced immune suppression and photocarcinogenesis: Chemoprevention by dietary botanical agents

    OpenAIRE

    Santosh K. Katiyar

    2007-01-01

    Studies of immune-suppressed transplant recipients and patients with biopsy-proven skin cancer have confirmed that ultraviolet (UV) radiation-induced immune suppression is a risk factor for the development of skin cancer in humans. UV radiation suppresses the immune system in several ways. The UVB spectrum inhibits antigen presentation, induces the release of immunosuppressive cytokines, and elicits DNA damage that is a molecular trigger of UV-mediated immunosuppression. It is therefore impor...

  17. 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

    2016-01-01

    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.

  18. 77 FR 28614 - Prospective Grant of Exclusive License: Development of Chemopreventive Treatments for Head and...

    Science.gov (United States)

    2012-05-15

    ... HUMAN SERVICES National Institutes of Health Prospective Grant of Exclusive License: Development of.... The prospective exclusive license territory may be worldwide and the field of use may be limited to... applications under consideration, for the prospective license territory and field of use to be granted...

  19. 77 FR 65699 - Prospective Grant of Exclusive License: Development of Chemopreventive Treatments for Head and...

    Science.gov (United States)

    2012-10-30

    ... for the instant technology was published in 77 FR 28614, Tuesday, May 15, 2012. Complete applications... HUMAN SERVICES National Institutes of Health Prospective Grant of Exclusive License: Development of... prospective exclusive evaluation option license territory may be worldwide and the field of use may be...

  20. The REDUCE trial: chemoprevention in prostate cancer using a dual 5alpha-reductase inhibitor, dutasteride.

    Science.gov (United States)

    Musquera, Mireia; Fleshner, Neil E; Finelli, Antonio; Zlotta, Alexandre R

    2008-07-01

    Dutasteride, a dual 5alpha-reductase inhibitor, is used in the treatment of benign prostatic hyperplasia (BPH). It reduces serum prostate-specific antigen levels by approximately 50% at 6 months and total prostate volume by 25% after 2 years. Randomized placebo-controlled trials in BPH patients have shown the efficacy of dutasteride in symptomatic relief, improvements in quality of life and peak urinary flow rate. Side effects occurring with dutasteride are decreased libido, erectile dysfunction, ejaculation disorders and gynecomastia. Preliminary data from placebo-controlled BPH trials have shown a decrease in the detection of prostate cancer in patients treated with dutasteride, although these studies were not designed to look at this issue. Dutasteride differs from finasteride in that it inhibits both isoenzymes of 5alpha-reductase, type I and type II. The landmark Prostate Cancer Prevention Trial at the end of the 7-year study demonstrated a 24.8% reduction in the incidence of prostate cancer in the finasteride group compared with placebo. However, a 25.5% increase in the prevalence of high-grade Gleason tumors has been observed, the clinical significance of which has been debated. Preliminary data suggest a decrease in prostate cancer incidence in dutasteride-treated patients and demonstrate type I alphareductase enzyme expression in prostate cancer. As a result, dutasteride is being investigated for prostate cancer prevention in the ongoing Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, which is discussed here. PMID:18588452

  1. 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.; Moesgaard, S.; Reid, M.; Rayman, M.

    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 by...

  2. Triple antioxidant SNEDDS formulation with enhanced oral bioavailability: Implication of chemoprevention of breast cancer.

    Science.gov (United States)

    Tripathi, Shailja; Kushwah, Varun; Thanki, Kaushik; Jain, Sanyog

    2016-08-01

    The present study aimed to develop quercetin, resveratrol and genistein loaded self-nanoemulsifying drug delivery system (SNEDDS) by QbD approach in order to improve their oral bioavailability and antioxidant potential. The size and PDI of the optimized formulation were found to be curve (AUC) of all three antioxidants. The SNEDDS demonstrated ~4.27 fold enhancement in oral bioavailability of quercetin, ~1.5 fold in case of resveratrol and ~2.8 fold in case of genistein as compared to free antioxidants suspension. Finally, the prophylactic antitumor efficacy of developed formulation was tested against DMBA induced breast cancer model in rats, which demonstrated enhanced abeyance towards the tumor growth as compared to free antioxidants. PMID:27033463

  3. Lipoxygenase and cyclooxygenase metabolism: new insights in treatment and chemoprevention of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Adrian Thomas E

    2003-01-01

    Full Text Available Abstract The essential fatty acids, linoleic acid and arachidonic acid play an important role in pancreatic cancer development and progression. These fatty acids are metabolized to eicosanoids by cyclooxygenases and lipoxygenases. Abnormal expression and activities of both cyclooxygenases and lipoxygenases have been reported in pancreatic cancer. In this article, we aim to provide a brief summary of (1 our understanding of the roles of these enzymes in pancreatic cancer tumorigenesis and progression; and (2 the potential of using cyclooxygenase and lipoxygenase inhibitors for pancreatic cancer treatment and prevention.

  4. Lipoxygenase and cyclooxygenase metabolism: new insights in treatment and chemoprevention of pancreatic cancer

    OpenAIRE

    Adrian Thomas E; Hennig Rene; Ding Xian-Zhong

    2003-01-01

    Abstract The essential fatty acids, linoleic acid and arachidonic acid play an important role in pancreatic cancer development and progression. These fatty acids are metabolized to eicosanoids by cyclooxygenases and lipoxygenases. Abnormal expression and activities of both cyclooxygenases and lipoxygenases have been reported in pancreatic cancer. In this article, we aim to provide a brief summary of (1) our understanding of the roles of these enzymes in pancreatic cancer tumorigenesis and pro...

  5. Chemopreventive Efficacy of Ginger (Zingiber Officinale) in Ethionine Induced Rat Hepatocarcinogenesis

    OpenAIRE

    Yusof, Yasmin Anum Mohd; Ahmad, Norliza; Das, Srijit; Sulaiman, Suhaniza; Murad, Nor Azian

    2008-01-01

    Ginger (Zingiber officinale Rosco) is widely used in foods as a spice all around the world. It has been reported to have antioxidant and anticarcinogenic properties. We investigated the effect of ginger in ethionine induced rat hepatocarcinogenesis. Male Wistar rats were divided into 5 groups: group 1 and 2 served as controls and they received normal rat chow and olive oil respectively. Group 3 was fed with ginger oleoresin dissolved in olive oil at 100 mg/kg body wt. Group 4 was fed with cho...

  6. Chemopreventive effect of Quercus infectoria against chemically induced renal toxicity and carcinogenesis

    OpenAIRE

    Rehman, Muneeb U.; Mir Tahir, Farrah Ali; Wajhul Qamar; Rehan Khan; Abdul Quaiyoom Khan; Abdul Lateef; Oday-O-Hamiza; Sarwat Sultana

    2012-01-01

    In this study we have shown that Quercus infectoria attenuates Fe- NTA induced renal oxidative stress, hyperproliferative response and renal carcinogenesis in rats. Fe-NTA promoted DEN (N-diethyl nitrosamine) initiated renal carcinogenesis by increasing the percentage incidence of tumors and induces early tumor markers viz. ornithine decarboxylase (ODC) level and PCNA expression. Fe- NTA (9 mg Fe/kg body weight, intraperitoneally) enhances renal Malondialdehyde, xanthine oxidase and hydrogen ...

  7. Role of probiotics, prebiotics and synbiotics in chemoprevention for colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Constantine Iosif Fotiadis; Christos Nikolaou Stoidis; Basileios Georgiou Spyropoulos; Eleftherios Dimitriou Zografos

    2008-01-01

    Colorectal cancer is the third most common form of cancer. Current treatments are all associated with a high risk of complications and a low success rate. Recently, synbiotics have been proposed as a new preventive and therapeutic option. There is no direct experimental evidence for cancer suppression in humans as a result of the consumption of pro-, pre-or synbiotics. However, there is a wealth of evidence emerging from laboratory studies. The mechanisms by which pro-, pre- and synbiotics may inhibit colon cancer are now beginning to be understood and will be addressed in the present review. C 2008 The WJG Press. All rights reserved.

  8. Proteasome inhibition as a new strategy in cancer therapy and chemoprevention 

    Directory of Open Access Journals (Sweden)

    Michał Maliński

    2013-02-01

    Full Text Available  The ubiquitin-proteasome system is one of the main pathways involved in degradation of cellular proteins and regulation of most biochemical processes critical for maintaining cellular homeostasis. Among proteins that undergo proteasomal degradation are those involved in signal transduction, metabolism regulation, cell cycle control and apoptosis. Therefore, inhibition of the ubiquitin-proteasome system causes inhibition of cell proliferation and induction of apoptosis, especially in cancer cells, which makes it a promising strategy of cancer therapy that is already supported by clinical trials. This article summarizes reports of known proteasome inhibitors, differing in chemical structure and mechanism of action, emphasizing their effects on intracellular phenomena related to apoptosis and cell cycle control.

  9. Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically active iron chelator

    OpenAIRE

    Jiao, Yan; Wilkinson, John; Di, Xiumin; Wang, Wei; Hatcher, Heather; Kock, Nancy D.; D'Agostino, Ralph; Knovich, Mary Ann; Torti, Frank M; Suzy V Torti

    2009-01-01

    Curcumin is a natural product currently in human clinical trials for a variety of neoplastic, preneoplastic, and inflammatory conditions. We previously observed that, in cultured cells, curcumin exhibits properties of an iron chelator. To test whether the chelator activity of curcumin is sufficient to induce iron deficiency in vivo, mice were placed on diets containing graded concentrations of both iron and curcumin for 26 weeks. Mice receiving the lowest level of dietary iron exhibited borde...

  10. Updates and Controversies in the Rapidly Evolving Field of Lung Cancer Screening, Early Detection, and Chemoprevention

    OpenAIRE

    Hasmeena Kathuria; Yaron Gesthalter; Avrum Spira; Brody, Jerome S.; Katrina Steiling

    2014-01-01

    Lung cancer remains the leading cause of cancer-related death in the United States. Cigarette smoking is a well-recognized risk factor for lung cancer, and a sustained elevation of lung cancer risk persists even after smoking cessation. Despite identifiable risk factors, there has been minimal improvement in mortality for patients with lung cancer primarily stemming from diagnosis at a late stage when there are few effective therapeutic options. Early detection of lung cancer and effective sc...

  11. Ornithine Decarboxylase-1 Polymorphism, Chemoprevention With Eflornithine and Sulindac, and Outcomes Among Colorectal Adenoma Patients

    OpenAIRE

    Zell, Jason A.; McLaren, Christine E.; Chen, Wen-Pin; Thompson, Patricia A.; Gerner, Eugene W.; Meyskens, Frank L.

    2010-01-01

    The ornithine decarboxylase-1 (ODC1) polymorphism at position +316 affects binding by transcriptional activators and repressors and modulates the risk of metachronous colorectal adenomas, particularly in association with aspirin use. We investigated the effects of ODC1 after treatment with difluoromethylornithine (eflornithine)/sulindac or placebo. Two hundred twenty-eight colorectal adenoma patients in a randomized phase III trial were genotyped for ODC1. We used Wilcoxon rank sums tests on ...

  12. Immunological Investigation for the Presence of Lunasin, a Chemopreventive Soybean Peptide, in the Seeds of Diverse Plants.

    Science.gov (United States)

    Alaswad, Alaa A; Krishnan, Hari B

    2016-04-13

    Lunasin, a 44 amino acid soybean bioactive peptide, exhibits anticancer and anti-inflammatory properties. All soybean varieties that have been examined contain lunasin. It has also been reported in a few other plant species including amaranth, black nightshade, wheat, barley, rye, and triticale. Interestingly, detailed searches of transcriptome and DNA sequence databases of cereals failed to identify lunasin-coding sequences, raising questions about the authenticity of lunasin in cereals. To clarify the presence or absence of lunasin in cereals and other plant species, an immunological investigation was conducted utilizing polyclonal antibodies raised against the first 20 amino acid N-terminal peptide (SKWQHQQDSCRKQLQGVNLT) and a 15 amino acid C-terminal peptide (CEKHIMEKIQGRGDD) of lunasin. Protein blot analyses revealed the presence of proteins from several plants that reacted against the lunasin N-terminal peptide antibodies. However, the same proteins failed to react against the lunasin C-terminal peptide antibodies. These results demonstrate that peptides identical to soybean lunasin are absent in seeds of diverse plants examined in this study. PMID:27015324

  13. Dietary Chemoprevention of PhIP Induced Carcinogenesis in Male Fischer 344 Rats with Tomato and Broccoli

    OpenAIRE

    Kirstie Canene-Adams; Sfanos, Karen S; Chung-Tiang Liang; Srinivasan Yegnasubramanian; Nelson, William G.; Cory Brayton; Marzo, Angelo M. De

    2013-01-01

    The heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-B]pyridine (PhIP), found in meats cooked at high temperatures, has been implicated in epidemiological and rodent studies for causing breast, prostate, and colorectal cancers. A previous animal study using a xenograft model has shown that whole tomato and broccoli, when eaten in combination, exhibit a marked effect on tumor reduction compared to when eaten alone. Our aim was to determine if PhIP-induced carcinogenesis can be prevente...

  14. Dietary chemoprevention of PhIP induced carcinogenesis in male Fischer 344 rats with tomato and broccoli.

    Directory of Open Access Journals (Sweden)

    Kirstie Canene-Adams

    Full Text Available The heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-B]pyridine (PhIP, found in meats cooked at high temperatures, has been implicated in epidemiological and rodent studies for causing breast, prostate, and colorectal cancers. A previous animal study using a xenograft model has shown that whole tomato and broccoli, when eaten in combination, exhibit a marked effect on tumor reduction compared to when eaten alone. Our aim was to determine if PhIP-induced carcinogenesis can be prevented by dietary consumption of whole tomato + broccoli powders. Male Fischer 344 rats (n = 45 were randomized into the following treatment groups: control (AIN93G diet, PhIP (200 ppm in AIN93G diet for the first 20 weeks of the study, or tomato + broccoli + PhIP (mixed in AIN93G diet at 10% each and fed with PhIP for 20 weeks, and then without PhIP for 32 weeks. Study animals were monitored for 52 weeks and were euthanized as necessary based on a set of criteria for health status and tumor burden. Although there appeared to be some hepatic and intestinal toxicity due to the combination of PhIP and tomato + broccoli, these rodents had improved survival and reduced incidence and/or severity of PhIP-induced neoplastic lesions compared to the PhIP-alone treated group. Rats eating tomato + broccoli exhibited a marked decrease in the number and size of cribiform prostatic intraepitheilial neoplasia/carcinoma in situ (cribiform PIN/CIS lesions and in the incidence of invasive intestinal adenocarcinomas and skin carcinomas. Although the apparent toxic effects of combined PhIP and tomato + broccoli need additional study, the results of this study support the hypothesis that a diet rich in tomato and broccoli can reduce or prevent dietary carcinogen-induced cancers.

  15. Dietary chemoprevention of PhIP induced carcinogenesis in male Fischer 344 rats with tomato and broccoli.

    Science.gov (United States)

    Canene-Adams, Kirstie; Sfanos, Karen S; Liang, Chung-Tiang; Yegnasubramanian, Srinivasan; Nelson, William G; Brayton, Cory; De Marzo, Angelo M

    2013-01-01

    The heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-B]pyridine (PhIP), found in meats cooked at high temperatures, has been implicated in epidemiological and rodent studies for causing breast, prostate, and colorectal cancers. A previous animal study using a xenograft model has shown that whole tomato and broccoli, when eaten in combination, exhibit a marked effect on tumor reduction compared to when eaten alone. Our aim was to determine if PhIP-induced carcinogenesis can be prevented by dietary consumption of whole tomato + broccoli powders. Male Fischer 344 rats (n = 45) were randomized into the following treatment groups: control (AIN93G diet), PhIP (200 ppm in AIN93G diet for the first 20 weeks of the study), or tomato + broccoli + PhIP (mixed in AIN93G diet at 10% each and fed with PhIP for 20 weeks, and then without PhIP for 32 weeks). Study animals were monitored for 52 weeks and were euthanized as necessary based on a set of criteria for health status and tumor burden. Although there appeared to be some hepatic and intestinal toxicity due to the combination of PhIP and tomato + broccoli, these rodents had improved survival and reduced incidence and/or severity of PhIP-induced neoplastic lesions compared to the PhIP-alone treated group. Rats eating tomato + broccoli exhibited a marked decrease in the number and size of cribiform prostatic intraepitheilial neoplasia/carcinoma in situ (cribiform PIN/CIS) lesions and in the incidence of invasive intestinal adenocarcinomas and skin carcinomas. Although the apparent toxic effects of combined PhIP and tomato + broccoli need additional study, the results of this study support the hypothesis that a diet rich in tomato and broccoli can reduce or prevent dietary carcinogen-induced cancers. PMID:24312188

  16. Interaction of alcohol and smoking in the pathogenesis of upper digestive tract cancers - possible chemoprevention with cysteine

    OpenAIRE

    Salaspuro, Ville

    2006-01-01

    Background: Alcohol consumption and smoking are the main causes of upper digestive tract cancers. These risk factors account for over 75% of all cases in developed countries. Epidemiological studies have shown that alcohol and tobacco interact in a multiplicative way to the cancer risk, but the pathogenetic mechanism behind this is poorly understood. Strong experimental and human genetic linkage data suggest that acetaldehyde is one of the major factors behind the carcinogenic effect. In the ...

  17. Chemopreventive Effect of Cinnamon Extract on Carbon Tetrachloride-Induced Physiological Changes in the Frog, Rana ridibunda

    Science.gov (United States)

    Al-Attar, Atef M.

    The present study examined the preventive influences of an aqueous extract of cinnamon on carbon tetrachloride-induced some physiological alterations in the frog, Rana ridibunda. The experimental animals were divided into five batches. The first batch was untreated and served as control. The other batches were treated for 6 weeks with carbon tetrachloride, cinnamon extract plus carbon tetrachloride, cinnamon and corn oil, respectively. Haematological, biochemical and hepatosomatic index indices were chosen as physiological indicators. These parameters were evaluated at 2, 4 and 6 weeks. In comparison with control and cinnamon plus CCl4 batches, significant decreases of red blood cell count, haemoglobin concentration, haematocrit, mean corpuscular haemoglobin concentration and increases of glutamic pyruvic acid transaminase values were noted in CCl4-exposed batch at all experimental periods. Also, glutamic oxaloacetic acid transaminase and hepatosomatic index levels were significantly elevated, while mean corpuscular haemoglobin values were decreased at second and last periods. Mean cell volume values were only increased at the first period. In comparison with control batch, significant decreases of red blood cell count, haemoglobin concentration, haematocrit, and increases of glutamic oxaloacetic acid transaminase, glutamic pyruvic acid transaminase and hepatosomatic index values were observed in frogs treated with cinnamon plus CCl4 at 2 and 6 weeks. Mean cell volume and mean corpuscular haemoglobin values were statistically elevated at second period. Mean corpuscular haemoglobin concentration values were declined at last period. Moreover, the percentage changes of these parameters in cinnamon plus CCl4 batch tended to be lower than CCl4 treated the experimental animals. In addition, it is conceivable therefore, that the cinnamon aqueous extract exhibits a protective influence against carbon tetrachloride-induced some physiological changes, probably mediated through different pathways.

  18. Inhibition of conjugated linoleic acid on mouse forestomach neoplasia induced by benzo (a) pyrene and chemopreventive mechanisms

    Institute of Scientific and Technical Information of China (English)

    Bing-Qing Chen; Ying-Ben Xue; Jia-Ren Liu; Yan-Mei Yang; Yu-Mei Zheng; Xuan-Lin Wang; Rui-Hai Liu

    2003-01-01

    AIM: To explore the inhibition of conjugated linoleic acidisomers in different purity (75 % purity c9,t11-, 98 % purityc9,t11- and 98 % purity t10,c12-CLA) on the formation offorestomach neoplasm and cheopreventive mechanisms.METHODS: Forestomach neoplasm model induced by B(a)P in KunMing mice was established. The numbers of tumorand diameter of each tumor in forestomach were counted;the mice plasma malondialdehyde (MDA) were measuredby TBARS assay; TUNEL assay was used to analyze theapoptosis in forestomach neoplasia and the expression ofMEK-1, ERK-1, MKP-1 protein in forestomach neoplasm werestudied by Western Blotting assay.RESULTS: The incidence of neoplasm in B(a)P group, 75 %purity c9, t11-CLA group, 98 % purity cg,t11-CLA groupand 98 % purity t10, c12-CLA group was 100 %, 75.0 %(P>0.05), 69.2 % (P<0.05) and 53.8 % (P<0.05) respectivelyand the effect of two CLA isomers in 98 % purity onforestomach neoplasia was significant; CLA showed noinfluence on the average tumor numbers in tumor-bearingmouse, but significantly decreased the tumor size, the tumoraverage diameter of mice in 75 % purity c9,t11-CLA group,98 % purity cg,t11-CLA group and 98 % purity t10, c12-CLAgroup was 0.157±0.047 cm, 0.127±0.038 cm and 0.128±0.077 cm (P<0.05) and 0.216±0.088 cm in B(a)P group;CLA could also significantly increase the apoptosis cellnumbers by 144.00±20.31, 153.75±23.25, 157.25±15.95(P<0.05) in 75 % purity c9,t11-CLA group, 98 % purity c9,t11-CLA group and 98 % purity t10,c12-CLA group (30.88±3.72 in BP group); but there were no significant differencesbetween the effects of 75 % purity c9,t11-CLA and twoisomers in 98 % purity on tumor size and apoptotic cellnumbers; the plasma levels of MDA in were increased by75 % purity c9,t11-ClA, 98 % purity c9,t11-CLA and 98 %purity t10,c12-CLA. The 75 % purity c9,t11-CLA showedstronger inhibition; CLA could also inhibit the expression ofERK-1 protein and promote the expression of MKP-1 protein,however no influence of CLA on MEK-1 protein was observed.CONCLUSION: Two isomers in 98 % purity show strongerinhibition on carcinogenesis. However, the inhibitorymechanisms of CLA on carcinogenesis is complicated, whichmay be due to the increased mice plasmaMDA, the inducingapoptosis in tumor tissues. And the effect of CLA on theexpression of ERK-1 and MKP-1 may be one of themechanisms of the inhibition of CLA on the tumor.

  19. Chemoprevention in gastrointestinal physiology and disease. Targeting the progression of cancer with natural products: a focus on gastrointestinal cancer.

    Science.gov (United States)

    Khoogar, Roxane; Kim, Byung-Chang; Morris, Jay; Wargovich, Michael J

    2016-05-01

    The last decade has witnessed remarkable progress in the utilization of natural products for the prevention and treatment of human cancer. Many agents now in the pipeline for clinical trial testing have evolved from our understanding of how human nutritional patterns account for widespread differences in cancer risk. In this review, we have focused on many of these promising agents arguing that they may provide a new strategy for cancer control: natural products once thought to be only preventive in their mode of action now are being explored for efficacy in tandem with cancer therapeutics. Natural products may reduce off-target toxicity of therapeutics while making cancers more amenable to therapy. On the horizon is the use of certain natural products, in their own right, as mitigants of late-stage cancer, a new frontier for small-molecule natural product drug discovery. PMID:26893159

  20. Chemopreventive and chemotherapeutic effect of dietary supplementation of vitamin D on cholangiocarcinoma in a Chemical-Induced animal model.

    Science.gov (United States)

    Chiang, Kun-Chun; Yeh, Chun-Nan; Lin, Kun-Ju; Su, Li-Jen; Yen, Tzu-Chen; Pang, Jong-Hwei S; Kittaka, Atsushi; Sun, Chi-Chin; Chen, Miin-Fu; Jan, Yi-Yin; Chen, Tai C; Juang, Horng-Heng; Yeh, Ta-Sen

    2014-06-15

    Intrahepatic cholangiocarcinoma (ICC) is an aggressive cancer. Vitamin D, a pro-hormone, is getting popular due to its hormone-like functions after converted to its active form, 1α,25(OH)2D3. Here, we show that dietary supplementation with 6 IU/g of vitamin D greatly suppressed ICC initiation and progression without apparent toxicity in a chemically induced rat model. Microarray analysis of rat ICC tissues showed vitamin D supplementation modulated the expressions of several unique genes, including lipocalin 2 (Lcn2), confirmed by RT-qPCR and immunohistochemical (IHC) staining. Further, 53 of 80 human ICC specimens (66%) exhibited high LCN2 expression and LCN2 knockdown in SNU308 cells decreased cell growth and migration, suggesting LCN2 be an oncogene in human ICC. As human ICC SNU1079 cells were treated by 1α,25(OH)2D3, LCN2 expression and cell proliferation were attenuated. The downregulation of LCN2 expression was blunted when vitamin D receptor (VDR) was knocked down, implicating that the in vivo Lcn2 downregulation is a direct consequence of vitamin D supplementation Our results support the prevailing concept that vitamin D status is negatively associated with cancer incidence and mortality and suggest LCN2 may be a potential target against ICC. Further studies of application of vitamin D or its analog against ICC are warranted. PMID:24939880

  1. Chemopreventive effect of Annona muricata on DMBA-induced cell proliferation in the breast tissues of female albino mice

    OpenAIRE

    J.B. Minari; U. Okeke

    2014-01-01

    Background: Breast cancer is the most common type of cancer and leading cause of cancer death in women. Breast cancer and cancer related diseases have been treated using surgery, chemotherapy, and radiation therapy, or a combination of these. Despite these therapeutic options, cancer remains associated with high mortality. Traditional medicine which involves the use of herbs has been used to treat various types of cancer and this has been found to be effective with minimal or no side effects....

  2. Chemopreventive Metabolites Are Correlated with a Change in Intestinal Microbiota Measured in A-T Mice and Decreased Carcinogenesis

    Science.gov (United States)

    Dowdy, Tyrone; Wang, Yiwen; Singh, Rajbir; Ruegger, Paul M.; Borneman, James; Fornace, Albert J.; Schiestl, Robert H.

    2016-01-01

    Intestinal microbiota play a significant role in nutrient metabolism, modulation of the immune system, obesity, and possibly in carcinogenesis, although the underlying mechanisms resulting in disease or impacts on longevity caused by different intestinal microbiota are mostly unknown. Herein we use isogenic Atm-deficient and wild type mice as models to interrogate changes in the metabolic profiles of urine and feces of these mice, which are differing in their intestinal microbiota. Using high resolution mass spectrometry approach we show that the composition of intestinal microbiota modulates specific metabolic perturbations resulting in a possible alleviation of a glycolytic phenotype. Metabolites including 3-methylbutyrolactone, kyneurenic acid and 3-methyladenine known to be onco-protective are elevated in Atm-deficient and wild type mice with restricted intestinal microbiota. Thus our approach has broad applicability to study the direct influence of gut microbiome on host metabolism and resultant phenotype. These results for the first time suggest a possible correlation of metabolic alterations and carcinogenesis, modulated by intestinal microbiota in A-T mice. PMID:27073845

  3. Honokiol, a chemopreventive agent against skin cancer, induces cell cycle arrest and apoptosis in human epidermoid A431 cells.

    Science.gov (United States)

    Chilampalli, Chandeshwari; Guillermo, Ruth; Kaushik, Radhey S; Young, Alan; Chandrasekher, Gudiseva; Fahmy, Hesham; Dwivedi, Chandradhar

    2011-11-01

    Honokiol is a plant lignan isolated from bark and seed cones of Magnolia officinalis. Recent studies from our laboratory indicated that honokiol pretreatment decreased ultraviolet B-induced skin cancer development in SKH-1 mice. The aim of the present investigation was to study the effects of honokiol on human epidermoid squamous carcinoma A431 cells and to elucidate possible mechanisms involved in preventing skin cancer. A431 cells were pretreated with different concentrations of honokiol for a specific time period and investigated for effects on apoptosis and cell cycle analysis. Treatment with honokiol significantly decreased cell viability and cell proliferation in a concentration- and time-dependent manner. Honokiol pretreatment at 50 μmol/L concentration induced G0/G1 cell cycle arrest significantly (P Cdk4 and Cdk6 proteins and up-regulated the expression of Cdk's inhibitor proteins p21 and p27. Pretreatment of A431 cells with honokiol leads to induction of apoptosis and DNA fragmentation. These findings indicate that honokiol provides its effects in squamous carcinoma cells by inducing cell cycle arrest at G0/G1 phase and apoptosis. PMID:21908486

  4. Chemo-preventive effect of Star anise in N-nitrosodiethylamine initiated and phenobarbital promoted hepato-carcinogenesis.

    Science.gov (United States)

    Yadav, Amit Singh; Bhatnagar, D

    2007-09-20

    The generation of free radicals is a cause of many pathological conditions like diabetes mellitus, cancer, stroke, etc. Free radicals cause damage to cellular DNA and initiate carcinogenesis. Free radicals also bring about proliferation of cells via cell signaling. An inverse relationship between the consumption of vegetable diets and the risk of cancer has been established. In the present study, Star anise (Illicium verum), which is a commonly used condiment in Indian cuisine, was assessed for its anti-carcinogenic potential in N-nitrosodiethylamine (NDEA) initiated and phenobarbital (PB) promoted hepato-carcinogenesis. Rats were randomly selected for eight experimental groups. The carcinogenesis was induced by injecting the rats, with a single dose of NDEA (200mg/kg body weight) intraperitoneally as initiator, followed by promotion with PB (0.05%) in drinking water for 14 consecutive weeks. The treatment with NDEA increased liver weight, while Star anise (Star) treatment reduced the liver weight of rats. The treatment with Star throughout for 20 weeks or during the promotion stage (6-20 weeks) significantly reduced the nodule incidence and nodule multiplicity in the rats, while the treatment with Star at the initiation phase (first 4 weeks) only could not reduce these parameters. The treatment with Star for 20 consecutive weeks significantly reduced the nodule size and nodule volume. The treatment with Star throughout as well as at the promotion stage lowered the lipid peroxidation (LPO) in liver and erythrocytes, while the LPO was not lowered, when Star was administered during initiation stage only. The treatment with Star restored the liver and erythrocyte super-oxide dismutase (SOD) activities to normal in the carcinogenesis-induced rats. The liver catalase (CAT) activity increased in all the treated groups. The erythrocyte CAT activity increased in the rats treated with Star during initiation and promotion stage only. The liver glutathione (GSH) level increased significantly in the groups treated with Star. The erythrocyte GSH level was lowered in the rats treated with NDEA and PB, however, Star treatment helped in increasing the erythrocyte GSH level to some extent. The liver and erythrocyte glutathione-S-transferase (GST) activity increased in all the groups treated with NDEA and PB. The treatment with Star decreased GST level significantly. These results indicate that the treatment with Star reduces the tumor burden, lowers oxidative stress and increases the level of phase II enzymes, which may contribute to its anti-carcinogenic potential. PMID:17658503

  5. Detection of Circulating Tumor DNA in the Blood of Cancer Patients: An Important Tool in Cancer Chemoprevention.

    Science.gov (United States)

    Ulz, Peter; Auer, Martina; Heitzer, Ellen

    2016-01-01

    Liquid biopsies represent novel promising tools to determine the impact of clonal heterogeneity on clinical outcomes with the potential to identify novel therapeutic targets in cancer patients. We developed a low-coverage whole-genome sequencing approach in order to noninvasively establish copy number aberrations in plasma DNA from metastasized cancer patients. Using plasma-Seq we were able to monitor genetic evolution including the acquirement of novel copy number changes, such as focal amplifications and chromosomal polysomies. The big advantage of our approach is that it can be performed on a benchtop sequencer, speed, and cost-effectiveness. Therefore, plasma-Seq represents an easy, fast, and affordable tool to provide the urgently needed genetic follow-up data. Here we describe our method including plasma DNA extraction, library preparation, and bioinformatic analyses. PMID:26608289

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

    International Nuclear Information System (INIS)

    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 (IC50 0.59 μM) 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 (IC50 70 nM) and 84 (IC50 36 nM). The aromatase inhibitory activities of these compounds are much more potent than that for the lead compound resveratrol, which has an IC50 of 80 μM. In addition to aromatase inhibitory activity, compounds 32 and 44 also displayed potent QR2 inhibitory activity (IC50 1.7 μM and 0.27 μM, 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.

  7. Current Experience in Testing Mitochondrial Nutrients in Disorders Featuring Oxidative Stress and Mitochondrial Dysfunction: Rational Design of Chemoprevention Trials

    Directory of Open Access Journals (Sweden)

    Giovanni Pagano

    2014-11-01

    Full Text Available An extensive number of pathologies are associated with mitochondrial dysfunction (MDF and oxidative stress (OS. Thus, mitochondrial cofactors termed “mitochondrial nutrients” (MN, such as α-lipoic acid (ALA, Coenzyme Q10 (CoQ10, and l-carnitine (CARN (or its derivatives have been tested in a number of clinical trials, and this review is focused on the use of MN-based clinical trials. The papers reporting on MN-based clinical trials were retrieved in MedLine up to July 2014, and evaluated for the following endpoints: (a treated diseases; (b dosages, number of enrolled patients and duration of treatment; (c trial success for each MN or MN combinations as reported by authors. The reports satisfying the above endpoints included total numbers of trials and frequencies of randomized, controlled studies, i.e., 81 trials testing ALA, 107 reports testing CoQ10, and 74 reports testing CARN, while only 7 reports were retrieved testing double MN associations, while no report was found testing a triple MN combination. A total of 28 reports tested MN associations with “classical” antioxidants, such as antioxidant nutrients or drugs. Combinations of MN showed better outcomes than individual MN, suggesting forthcoming clinical studies. The criteria in study design and monitoring MN-based clinical trials are discussed.

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

    OpenAIRE

    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 f...

  9. 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.

  10. 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, bo

  11. A novel protein fraction from Sesbania grandiflora shows potential anticancer and chemopreventive efficacy, in vitro and in vivo.

    Science.gov (United States)

    Laladhas, Krishna P; Cheriyan, Vino T; Puliappadamba, Vineshkumar T; Bava, Smitha V; Unnithan, Rajesh G; Vijayammal, Parvathy L; Anto, Ruby John

    2010-03-01

    We report mechanism-based evidence for the anticancer efficacy of a protein fraction, SF2 (Sesbania fraction 2) isolated from the flower of the medicinal plant, Sesbania grandiflora (S. grandiflora). The fraction was evaluated in two murine ascites tumour cell lines and human cancer cell lines of different origin for its anticancer effect. SF2 inhibited cell proliferation and induced apoptosis as demonstrated by DNA fragmentation and externalization of phosphatidyl serine in Daltons lymphoma ascites (DLA) and colon cancer cells (SW-480). Sensitivity to SF2 in these cells was associated with activation of caspases 3, 8 and 9, poly (ADP-ribose) polymerase cleavage and cytochrome C release which attests apoptosis induced cell death. Mechanistically, SF2 down-regulated phorbol myristate acetate (PMA) induced NF-kappaB, a transcription factor which controls the expression of genes encoding proteins involved in cell regulation and growth control. Additionally, SF2 also down-regulated anti-apoptotic factors such as Bcl-2, p-Akt and cyclooxygenase-2 induced by the tumour promoter PMA suggestive of a possible explanation for its anticancer effect. In vivo studies using ascites and solid tumour models strongly support in vitro findings as SF2 administration increased the life span and decreased the tumour volume in mice bearing tumour. In vivo toxicological evaluation revealed the pharmacological safety of SF2 and may serve as a potential anticancer drug candidate. PMID:19183244

  12. Molecular, cellular and medical aspects of the action of nutraceuticals and small molecules therapeutics: from chemoprevention to new drug development.

    Science.gov (United States)

    Colic, M; Pavelic, K

    2002-01-01

    Dietary supplements, functional foods and their concentrated, sometimes purified, active forms, the so-called nutraceuticals, are becoming increasingly popular throughout the world. Small molecules that regulate signal transduction cascades and gene expression are being tested by many pharmaceutical companies. A rapidly and exponentially growing industry (close to $30 billion in 1999 worldwide) exists to commercialize and exploit this interest. However, the scientific basis of the action of such unproved products is in the very early stages of development. While supporters claim they produce miracle cures, opponents argue that such unproved agents do more harm than good. PMID:12635491

  13. A study of chemopreventive effects of Emblica officinalis Linn. against radiation and lead induced haematological changes in Swiss albino mice

    International Nuclear Information System (INIS)

    The vast potential of radiant energy opens vistas of new horizons as its use in various fields of science, technology, therapeutics and diagnosis. However its also exposes the global population to the hazards of nuclear accidents and radiation injury. In this era of nuclear science it has become a prerequisite to know the effects of radiation on mankind and to develop effective countermeasures for minimizing the damages of radiation exposure. Heavy metals like lead can cause deleterious effects when its concentration goes beyond the limit in ecosystem. The combined effects of radiation and lead further increases the causation of damages to organs and tissues. Amla is found to be a non toxic, inexpensive, easily available herbal drug. Therefore present study was pertain to evaluate the chemo preventive role of Amla against radiation and lead induced changes in blood of Swiss albino mice. The animals were exposed to 6.0 Gy of gamma rays and with or without lead acetate which was given to them adlibitum. The Emblica was administered seven days prior to irradiation or lead acetate treatment. Three animals were sacrificed from all the experimental group at each post treatment intervals of 1, 2, 4, 7, 14 and 28 days by cervical dislocation . The blood was collected in heparinised tube for estimating various haematological parameters. The value of RBC, WBC, PCV, Hemoglobin, and MCV decreased up to day-14 in non drug treated groups and day-7 in drug treated groups, thereafter the value increased. When the animals treated with radiation and lead simultaneously synergistic effects were observed. The Amla treated groups showed early and fast recovery thus, it may deduce from above observation that Amla has potential to check the alteration produced by radiation and lead in the blood of Swiss albino mice. (author)

  14. Aspirin and salicylic acid decrease c-Myc expression in cancer cells: a potential role in chemoprevention.

    Science.gov (United States)

    Ai, Guoqiang; Dachineni, Rakesh; Muley, Pratik; Tummala, Hemachand; Bhat, G Jayarama

    2016-02-01

    Epidemiological studies have demonstrated a significant correlation between regular aspirin use and reduced colon cancer incidence and mortality; however, the pathways by which it exerts its anti-cancer effects are still not fully explored. We hypothesized that aspirin's anti-cancer effect may occur through downregulation of c-Myc gene expression. Here, we demonstrate that aspirin and its primary metabolite, salicylic acid, decrease the c-Myc protein levels in human HCT-116 colon and in few other cancer cell lines. In total cell lysates, both drugs decreased the levels of c-Myc in a concentration-dependent fashion. Greater inhibition was observed in the nucleus than the cytoplasm, and immunofluorescence studies confirmed these observations. Pretreatment of cells with lactacystin, a proteasome inhibitor, partially prevented the downregulatory effect of both aspirin and salicylic acid, suggesting that 26S proteasomal pathway is involved. Both drugs failed to decrease exogenously expressed DDK-tagged c-Myc protein levels; however, under the same conditions, the endogenous c-Myc protein levels were downregulated. Northern blot analysis showed that both drugs caused a decrease in c-Myc mRNA levels in a concentration-dependent fashion. High-performance liquid chromatography (HPLC) analysis showed that aspirin taken up by cells was rapidly metabolized to salicylic acid, suggesting that aspirin's inhibitory effect on c-Myc may occur through formation of salicylic acid. Our result suggests that salicylic acid regulates c-Myc level at both transcriptional and post-transcription levels. Inhibition of c-Myc may represent an important pathway by which aspirin exerts its anti-cancer effect and decrease the occurrence of cancer in epithelial tissues. PMID:26314861

  15. Cellular stress response: a novel target for chemoprevention and nutritional neuroprotection in aging, neurodegenerative disorders and longevity.

    Science.gov (United States)

    Calabrese, Vittorio; Cornelius, Carolin; Mancuso, Cesare; Pennisi, Giovanni; Calafato, Stella; Bellia, Francesco; Bates, Timothy E; Giuffrida Stella, Anna Maria; Schapira, Tony; Dinkova Kostova, Albena T; Rizzarelli, Enrico

    2008-12-01

    The predominant molecular symptom of aging is the accumulation of altered gene products. Moreover, several conditions including protein, lipid or glucose oxidation disrupt redox homeostasis and lead to accumulation of unfolded or misfolded proteins in the aging brain. Alzheimer's and Parkinson's diseases or Friedreich ataxia are neurological diseases sharing, as a common denominator, production of abnormal proteins, mitochondrial dysfunction and oxidative stress, which contribute to the pathogenesis of these so called "protein conformational diseases". The central nervous system has evolved the conserved mechanism of unfolded protein response to cope with the accumulation of misfolded proteins. As one of the main intracellular redox systems involved in neuroprotection, the vitagene system is emerging as a neurohormetic potential target for novel cytoprotective interventions. Vitagenes encode for cytoprotective heat shock proteins (Hsp) Hsp70 and heme oxygenase-1, as well as thioredoxin reductase and sirtuins. Nutritional studies show that ageing in animals can be significantly influenced by dietary restriction. Thus, the impact of dietary factors on health and longevity is an increasingly appreciated area of research. Reducing energy intake by controlled caloric restriction or intermittent fasting increases lifespan and protects various tissues against disease. Genetics has revealed that ageing may be controlled by changes in intracellular NAD/NADH ratio regulating sirtuin, a group of proteins linked to aging, metabolism and stress tolerance in several organisms. Recent findings suggest that several phytochemicals exhibit biphasic dose responses on cells with low doses activating signaling pathways that result in increased expression of vitagenes encoding survival proteins, as in the case of the Keap1/Nrf2/ARE pathway activated by curcumin and NAD/NADH-sirtuin-1 activated by resveratrol. Consistently, the neuroprotective roles of dietary antioxidants including curcumin, acetyl-L-carnitine and carnosine have been demonstrated through the activation of these redox-sensitive intracellular pathways. Although the notion that stress proteins are neuroprotective is broadly accepted, still much work needs to be done in order to associate neuroprotection with specific pattern of stress responses. In this review the importance of vitagenes in the cellular stress response and the potential use of dietary antioxidants in the prevention and treatment of neurodegenerative disorders is discussed. PMID:18629638

  16. CHEMOPREVENTIVE EFFICACY OF NAPROXEN AND NO-NAPROXEN IN RODENT MODELS OF COLON, URINARY BLADDER, AND MAMMARY CANCERS

    OpenAIRE

    Steele, Vernon E; RAO, CHINTHALAPALLY V.; Zhang, Yuting; Patlolla, Jagan; Boring, Daniel; Kopelovich, Levy; Juliana, M. Margaret; Grubbs, Clinton J; Lubet, Ronald A

    2009-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) have been highly effective in preventing colon, urinary bladder, and skin cancer preclinically; and also in clinical trials of colon adenoma formation. However, certain NSAIDs cause gastrointestinal (GI) ulceration and may increase cardiovascular (CV) events. Naproxen appears to cause the lowest CV events of the common NSAIDs other than aspirin. NO-naproxen was tested based on the finding that adding a nitric oxide (NO) group to NSAIDs may help al...

  17. MicroRNA alterations in Barrett′s esophagus, esophageal adenocarcinoma, and esophageal adenocarcinoma cell lines following cranberry extract treatment: Insights for chemoprevention

    Directory of Open Access Journals (Sweden)

    Laura A Kresty

    2011-01-01

    Full Text Available Background: Aberrant expression of small noncoding endogenous RNA molecules known as microRNAs (miRNAs is documented to occur in multiple cancer types including esophageal adencarcinoma (EAC and its only known precursor, Barrett′s esophagus (BE. Recent studies have linked dysregulation of specific miRNAs to histological grade, neoplastic progression and metastatic potential. Materials and Methods: Herein, we present a summary of previously reported dysregulated miRNAs in BE and EAC tissues as well as EAC cell lines and evaluate a cranberry proanthocyanidin rich extract′s (C-PAC ability to modulate miRNA expression patterns of three human EAC cell lines (JHEso-Ad-1, OE33 and OE19. Results: A review of 13 published studies revealed dysregulation of 87 miRNAs in BE and EAC tissues, whereas 52 miRNAs have been reported to be altered in BE or EAC cell lines, with 48% overlap with miRNA changes reported in tissues. We report for the first time C-PAC-induced modulation of five miRNAs in three EAC cell lines resulting in 26 validated gene targets and identification of key signaling pathways including p53, angiogenesis, T-cell activation and apoptosis. Additionally, mutiple cancer related networks were ideintified as modulated by C-PAC utilizing Kyoto Encyclopedia of Genes and Genomes (KEGG, Protein Analysis Through Evolutionary Relationships (PANTHER, and MetaCore analysis tools. Conclusions: Study results support the cancer inhibitory potential of C-PAC is in part attributable to C-PAC′s ability to modify miRNA profiles within EAC cells. A number of C-PAC-modulated miRNAs have been been identified as dysregulated in BE and EAC. Further insights into miRNA dysregulation and modulation by select cancer preventive agents will support improved targeted interventions in high-risk cohorts.

  18. Chemopreventive activity of compounds extracted from Casearia sylvestris (Salicaceae) Sw against DNA damage induced by particulate matter emitted by sugarcane burning near Araraquara, Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Prieto, A.M. [UNESP — Univ. Estadual Paulista, College of Pharmaceutical Sciences, Department of Clinical Analysis, Rua Expedicionários do Brasil, 1621, Araraquara (Brazil); Santos, A.G. [UNESP — Univ. Estadual Paulista, College of Pharmaceutical Sciences, Department of Natural Principles and Toxicology, Rodovia Araraquara-Jau, km 01, Araraquara (Brazil); Csipak, A.R.; Caliri, C.M.; Silva, I.C. [UNESP — Univ. Estadual Paulista, College of Pharmaceutical Sciences, Department of Clinical Analysis, Rua Expedicionários do Brasil, 1621, Araraquara (Brazil); Arbex, M.A. [UNIFESP — Federal University of São Paulo, Paulista College of Medicine, Department of Internal Medicine, Rua Pedro de Toledo, 720, São Paulo (Brazil); Silva, F.S.; Marchi, M.R.R. [UNESP — Univ. Estadual Paulista, Chemistry Institute, Department of Analytical Chemistry, Rua Francisco Degni, S/N, Araraquara (Brazil); Cavalheiro, A.J.; Silva, D.H.S.; Bolzani, V.S. [UNESP — Univ. Estadual Paulista, Chemistry Institute, Department of Organic Chemistry, Rua Francisco Degni, S/N, Araraquara (Brazil); Soares, C.P., E-mail: soarescp@hotmail.com [UNESP — Univ. Estadual Paulista, College of Pharmaceutical Sciences, Department of Clinical Analysis, Rua Expedicionários do Brasil, 1621, Araraquara (Brazil)

    2012-12-15

    Ethanolic extract of Casearia sylvestris is thought to be antimutagenic. In this study, we attempted to determine whether this extract and casearin X (a clerodane diterpene from C. sylvestris) are protective against the harmful effects of airborne pollutants from sugarcane burning. To that end, we used the Tradescantia micronucleus test in meiotic pollen cells of Tradescantia pallida, the micronucleus test in mouse bone marrow cells, and the comet assay in mouse blood cells. The mutagenic compound was total suspended particulate (TSP) from air. For the Tradescantia micronucleus test, T. pallida cuttings were treated with the extract at 0.13, 0.25, or 0.50 mg/ml. Subsequently, TSP was added at 0.3 mg/ml, and tetrads from the inflorescences were examined for micronuclei. For the micronucleus test in mouse bone marrow cells and the comet assay in mouse blood cells, Balb/c mice were treated for 15 days with the extract—3.9, 7.5, or 15.0 mg/kg body weight (BW)—or with casearin X—0.3, 0.25, or 1.2 mg/kg BW—after which they received TSP (3.75 mg/kg BW). In T. pallida and mouse bone marrow cells, the extract was antimutagenic at all concentrations tested. In mouse blood cells, the extract was antigenotoxic at all concentrations, whereas casearin X was not antimutagenic but was antigenotoxic at all concentrations. We conclude that C. sylvestris ethanolic extract and casearin X protect DNA from damage induced by airborne pollutants from sugarcane burning. -- Highlights: ► We assessed DNA protection of C. sylvestris ethanolic extract. ► We assessed DNA protection of casearin X. ► We used Tradescantia pallida micronucleus test as screening. ► We used comet assay and micronucleus test in mice. ► The compounds protected DNA against sugar cane burning pollutants.

  19. Thymoquinone subdues tumor growth and potentiates the chemopreventive effect of 5-fluorouracil on the early stages of colorectal carcinogenesis in rats

    OpenAIRE

    El-Shemi, Adel

    2016-01-01

    Osama Adnan Kensara,1,* Adel Galal El-Shemi,2,3,* Amr Mohamed Mohamed,2,4 Bassem Refaat,2 Shakir Idris,2 Jawwad Ahmad2 1Department of Clinical Nutrition, Faculty of Applied Medical Sciences, Umm Al-Qura University, Holy Makkah, Saudi Arabia; 2Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Umm Al-Qura University, Holy Makkah, Saudi Arabia; 3Department of Pharmacology, Faculty of Medicine, Assiut University, Assiut, Egypt; 4Department of Animal Medicine, Faculty of Vet...

  20. 冬凌草甲素抗肿瘤机制实验研究概况%Molecule mechanisms of Oridonin on tumors chemoprevention and therapy

    Institute of Scientific and Technical Information of China (English)

    王珍妮; 沃兴德; 周永列

    2008-01-01

    冬凌草甲素(Oridonin)有明显的抗肿瘤作用,既可以抑制细胞增殖,抑制核转录因子-KB(NF-KB),丝裂原活化蛋白激酶(MAPK),表皮生长因子受体等相关信号通路防止肿瘤发生,诱导细胞凋亡,也可以抑制毒性药物损伤自身细胞DNA,增强吞噬细胞吞噬作用等,有望成为一种天然抗癌新药.

  1. Induction of cancer chemopreventive enzymes by coffee is mediated by transcription factor Nrf2. Evidence that the coffee-specific diterpenes cafestol and kahweol confer protection against acrolein

    International Nuclear Information System (INIS)

    Mice fed diets containing 3% or 6% coffee for 5 days had increased levels of mRNA for NAD(P)H:quinone oxidoreductase 1 (NQO1) and glutathione S-transferase class Alpha 1 (GSTA1) of between 4- and 20-fold in the liver and small intestine. Mice fed 6% coffee also had increased amounts of mRNA for UDP-glucuronosyl transferase 1A6 (UGT1A6) and the glutamate cysteine ligase catalytic (GCLC) subunit of between 3- and 10-fold in the small intestine. Up-regulation of these mRNAs was significantly greater in mice possessing Nrf2 (NF-E2 p45 subunit-related factor 2) than those lacking the transcription factor. Basal levels of mRNAs for NQO1, GSTA1, UGT1A6 and GCLC were lower in tissues from nrf2-/- mice than from nrf2+/+ mice, but modest induction occurred in the mutant animals. Treatment of mouse embryonic fibroblasts (MEFs) from nrf2+/+ mice with either coffee or the coffee-specific diterpenes cafestol and kahweol (C + K) increased NQO1 mRNA up to 9-fold. MEFs from nrf2-/- mice expressed less NQO1 mRNA than did wild-type MEFs, but NQO1 was induced modestly by coffee or C + K in the mutant fibroblasts. Transfection of MEFs with nqo1-luciferase reporter constructs showed that induction by C + K was mediated primarily by Nrf2 and required the presence of an antioxidant response element in the 5'-upstream region of the gene. Luciferase reporter activity did not increase following treatment of MEFs with 100 μmol/l furan, suggesting that this ring structure within C + K is insufficient for gene induction. Priming of nrf2+/+ MEFs, but not nrf2-/- MEFs, with C + K conferred 2-fold resistance towards acrolein

  2. Development and In Vitro Evaluation of Vitamin E-Enriched Nanoemulsion Vehicles Loaded with Genistein for Chemoprevention Against UVB-Induced Skin Damage.

    Science.gov (United States)

    Brownlow, Bill; Nagaraj, Vinay J; Nayel, Amy; Joshi, Megha; Elbayoumi, Tamer

    2015-10-01

    There is a great need for effective protection against cutaneous pathologies arising from chronic exposure to harmful solar UVB radiations. A promising pharmaceutical strategy to improve the efficacy of chemotherapeutic/preventative natural compounds (e.g., soy isoflavone Genistein, Gen) is to enhance their dermal delivery using nanoemulsion (NE) formulations. This report investigates the development of nanoemulsified tocotrienol(T3)-rich fraction of red palm oil (Tocomin®), to yield an optimal NE delivery system for dermal photoprotection (z-average size cream forms. Gen-Tocomin® NE also showed excellent biocompatibility, and provided substantial UVB protection to cultured subcutaneous L929 fibroblasts, indicating the great potential of our Tocomin® NE warranting further prototype development as topical pharmaceutical platform for skin photoprotection applications. PMID:26108889

  3. Chemopreventive Effect of Dietary Glutamineon Colitis-Associated Colorectal Cancer Is Associated with Modulation of the DEPTOR/mTOR Signaling Pathway

    OpenAIRE

    Yun Tian; Keming Wang; Yingrui Fan; Yan Wang; Liqun Sun; Li Wang; Jirong Wang; Zhaoxia Wang; Juan Li; Ying Ye; Guozhong Ji

    2016-01-01

    Glutamine plays a protective role in colitis and colitis-associated colorectal cancer (CAC); however, the protective mechanisms are largely unknown to date. DEP domain-containing mTOR-interacting protein (DEPTOR)/mammalian Target of Rapamycin (mTOR) signaling plays an important role in carcinogenesis. The present study investigated the potential molecular mechanisms for the protective effect of glutamine in a murine model of azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CAC. The eff...

  4. Prospects, achievements, challenges and opportunities for scaling-up malaria chemoprevention in pregnancy in Tanzania: the perspective of national level officers

    DEFF Research Database (Denmark)

    Mubyazi, Godfrey; Bygbjerg, Ib; Magnussen, Pascal;

    2008-01-01

    -depth interviews were made with national level malaria control officers in 2006 and 2007. Data was analysed manually using a qualitative content analysis approach. Results: IPTp has been under implementation countrywide since 2001 and the 2005 evaluation report showed increased coverage of women taking two doses...... skills of most HWs and their poor motivation. Other problems were unreliable supply of free SP at private clinics, clean and safe water shortage at many government ANC clinics limiting direct observation treatment and occasionally pregnant women asked to pay for ANC services. Finally, supervision of....... Necessary concerted efforts towards fostering uptake and coverage of two IPTp doses were emphasized by the national level officers, who called for further action including operational health systems research to understand challenges and suggest ways forward for effective implementation and high coverage of...

  5. Potential Impact of Seasonal Malaria Chemoprevention on the Acquisition of Antibodies Against Glutamate-Rich Protein and Apical Membrane Antigen 1 in Children Living in Southern Senegal

    DEFF Research Database (Denmark)

    Ndiaye, Magatte; Sylla, Khadime; Sow, Doudou;

    2015-01-01

    -pyrimethamine (SP) combined with amodiaquine (AQ) is a promising strategy to control malaria morbidity in areas of highly seasonal malaria transmission. However, a concern is whether SMC can delay the natural acquisition of immunity toward malaria parasites in areas with intense SMC delivery. To investigate this......, total IgG antibody (Ab) responses to Plasmodium falciparum antigens glutamate-rich protein R0 (GLURP-R0) and apical membrane antigen 1 (AMA-1) were measured by enzyme-linked immunosorbent assay in Senegalese children under the age of 10 years in 2010 living in Saraya and Velingara districts (with SMC...

  6. Chemopreventive effect of myrtenal on bacterial enzyme activity and the development of 1,2-dimethyl hydrazine-induced aberrant crypt foci in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Lokesh Kumar Booupathy

    2016-01-01

    Full Text Available Colon cancer remains as a serious health problem around the world despite advances in diagnosis and treatment. Dietary fibers are considered to reduce the risk of colon cancer as they are converted to short chain fatty acids by the presence of anaerobic bacteria in the intestine, but imbalanced diet and high fat consumption may promote tumor formation at different sites, including the large bowel via increased bacterial enzymes activity. The present study was conducted to characterize the inhibitory action of myrtenal on bacterial enzymes and aberrant crypt foci (ACF. Experimental colon carcinogenesis induced by 1,2-dimethylhydrazine is histologically, morphologically, and anatomically similar to human colonic epithelial neoplasm. Discrete microscopic mucosal lesions such as ACF and malignant tumors function as important biomarkers in the diagnosis of colon cancer. Methylene blue staining was carried out to visualize the impact of 1,2-dimethylhydrazine and myrtenal. Myrtenal-treated animals showed decreased levels of bacterial enzymes such as β-glucuronidase, β-glucosidase, and mucinase. Characteristic changes in the colon were noticed by inhibiting ACF formation in the colon. In conclusion, treatment with myrtenal provided altered pathophysiological condition in colon cancer-bearing animals with evidence of decreased crypt multiplicity and tumor progression.

  7. The effect of transdermal estradiol or oral conjugated oestrogen and fenretinide versus placebo on haemostasis and cardiovascular risk biomarkers in a randomized breast cancer chemoprevention trial

    OpenAIRE

    Lazzeroni, M; Macis, D; Decensi, A.; Gandini, S; Sandri, MT; Serrano, D.; Guerrieri-Gonzaga, A; H. Johansson; Mora, S.; Daldoss, C; Omodei, U; Bonanni, B.

    2008-01-01

    Background: We have previously reported the favourable effect of transdermal estradiol (E2), relative to oral conjugated equine oestrogen (CEE), on ultrasensitive C-reactive protein after 12 months of treatment in a retinoid-placebo controlled two-by-two randomized breast cancer prevention trial (Decensi A et al (2002) Circulation 106 10 1224–8). Here, we investigate the changes in lipids and clotting profile in patients of the same trial. Methods and results: Recent post-menopausal women wer...

  8. The Architecture and Function of Monoclonal Antibody-Functionalized Mesoporous Silica Nanoparticles Loaded with Mifepristone: Repurposing Abortifacient for Cancer Metastatic Chemoprevention.

    Science.gov (United States)

    Gao, Yu; Gu, Songen; Zhang, Yingying; Xie, Xiaodong; Yu, Ting; Lu, Yusheng; Zhu, Yewei; Chen, Wenge; Zhang, Huijuan; Dong, Haiyan; Sinko, Patrick J; Jia, Lee

    2016-05-01

    The circulating tumor cells (CTCs) existing in cancer survivors are considered the root cause of cancer metastasis. To prevent the devastating metastasis cascade from initiation, we hypothesize that a biodegradable nanomaterial loaded with the abortifacient mifepristone (MIF) and conjugated with the epithelial cell adhesion molecule antibody (aEpCAM) may serve as a safe and effective cancer metastatic preventive agent by targeting CTCs and preventing their adhesion-invasion to vascular intima. It is demonstrated that MIF-loaded mesoporous silica nanoparticles (MSN) coated with aEpCAM (aE-MSN-M) can specifically target and bind colorectal cancer cells in either cell medium or blood through EpCAM recognition proven by quantitative flow cytometric detection and free aEpCAM competitive assay. The specific binding results in downregulation of the captured cells and drives them into G0/G1 phase primarily attributed to the effect of aEpCAM. The functional nanoparticles significantly inhibit the heteroadhesion between cancer cells and endothelial cells, suggesting the combined inhibition effects of aEpCAM and MIF on E-selectin and ICAM-1 expression. The functionalized nanoparticles circulate in mouse blood long enough to deliver MIF and inhibit lung metastasis. The present proof-of-concept study shows that the aE-MSN-M can prevent cancer metastasis by restraining CTC activity and their adhesion-invasion to vascular intima. PMID:27027489

  9. Modulation of xenobiotic metabolising enzymes by anticarcinogens-focus on glutathione S-transferases and their role as targets of dietary chemoprevention in colorectal carcinogenesis

    International Nuclear Information System (INIS)

    There is evidence that consumption of certain dietary ingredients may favourably modulate biotransformation of carcinogens. Associated with this is the hypothesis that the risk for developing colorectal cancer could be reduced, since its incidence is related to diet. Two main groups of biotransformation enzymes metabolize carcinogens, namely Phase I enzymes, which convert hydrophobic compounds to more water-soluble moieties, and Phase II enzymes (e.g. glutathione S-transferases [GST]), which primarily catalyze conjugation reactions. The conjugation of electrophilic Phase I intermediates with glutathione, for instance, frequently results in detoxification. Several possible colon carcinogens may serve as substrates for GST isoenzymes that can have marked substrate specificity. The conjugated products could be less toxic/genotoxic if GSTs are induced, thereby reducing exposure. Thus, numerous studies have shown that the induction of GSTs by antioxidants enables experimental animals to tolerate exposure to carcinogens. One important mechanism of GST induction involves an antioxidant-responsive response element (ARE) and the transcription factor nuclear factor E2-related factor 2 (Nrf2), which is bound to the Kelch-like ECH associated protein 1 (Keap1) in the cytoplasm. Antioxidants may disrupt the Keap-Nrf2 complex, allowing Nrf2 to translocate to the nucleus and mediate expression of Phase II genes via interaction with the ARE. GSTs are also induced by butyrate, a product of gut flora-derived fermentation of plant foods, which may act via different mechanisms, e.g. by increasing histone acetylation. GSTs are expressed with high inter-individual variability in human colonocytes, which points to large differences in cellular susceptibility to xenobiotics. Enhancing expression of GSTs in human colon tissue could therefore contribute to reducing cancer risks. However, it has not been demonstrated in humans that this mechanism is associated with cancer prevention. In the future, it will be useful to determine GSTs during dietary intervention studies to enhance our understanding of this protective mechanism

  10. Consumption of argan oil (Morocco) with its unique profile of fatty acids, tocopherols, squalene, sterols and phenolic compounds should confer valuable cancer chemopreventive effects.

    Science.gov (United States)

    Khallouki, F; Younos, C; Soulimani, R; Oster, T; Charrouf, Z; Spiegelhalder, B; Bartsch, H; Owen, R W

    2003-02-01

    The aim of this study was to evaluate the fatty acids, tocopherols, squalene, sterols and phenolic antioxidants in three types of argan oil (Moroccan food, Moroccan aesthetic and a French commercial variety) along with a basic comparison with extra virgin olive and sunflower oil. The fatty acid profiles in the argan oils were very similar, with oleic acid (43%) and linoleic acid (36%) and their respective monoacylglycerols predominating. The major vitamer identified was -tocopherol with a mean of 483+/-11 mg/kg, in contrast to -tocopherol, which is the major vitamer in olive (190+/-1 mg/kg) and sunflower oil (532+/-6 mg/kg). The squalene content of the argan oils was very similar with a mean of 313+/-4 mg/100 g, which is lower than that of the olive oil (499 mg/100 g) but significantly higher than in the sunflower oil (6 mg/100 g). In contrast to olive and sunflower oils in which -sitosterol is predominant, the major sterols detected in the argan oils were schottenol (mean 147+/-10 mg/kg) and spinasterol (mean 122+/-10 mg/kg). The only phenolic compounds other than the tocopherol vitamers which could be readily detected and quantitated were vanillic, syringic and ferulic (probably conjugated to glucose) acids along with tyrosol. In contrast to the extra virgin olive oil (793 mg/kg), the concentration of total phenolic compounds is extremely low (argan oil with its high content of the vitamer -tocopherol, squalene and oleic acid is likely to enhance the cancer prevention effects of the Moroccan diet. PMID:12548113

  11. Chemopreventive activity of compounds extracted from Casearia sylvestris (Salicaceae) Sw against DNA damage induced by particulate matter emitted by sugarcane burning near Araraquara, Brazil

    International Nuclear Information System (INIS)

    Ethanolic extract of Casearia sylvestris is thought to be antimutagenic. In this study, we attempted to determine whether this extract and casearin X (a clerodane diterpene from C. sylvestris) are protective against the harmful effects of airborne pollutants from sugarcane burning. To that end, we used the Tradescantia micronucleus test in meiotic pollen cells of Tradescantia pallida, the micronucleus test in mouse bone marrow cells, and the comet assay in mouse blood cells. The mutagenic compound was total suspended particulate (TSP) from air. For the Tradescantia micronucleus test, T. pallida cuttings were treated with the extract at 0.13, 0.25, or 0.50 mg/ml. Subsequently, TSP was added at 0.3 mg/ml, and tetrads from the inflorescences were examined for micronuclei. For the micronucleus test in mouse bone marrow cells and the comet assay in mouse blood cells, Balb/c mice were treated for 15 days with the extract—3.9, 7.5, or 15.0 mg/kg body weight (BW)—or with casearin X—0.3, 0.25, or 1.2 mg/kg BW—after which they received TSP (3.75 mg/kg BW). In T. pallida and mouse bone marrow cells, the extract was antimutagenic at all concentrations tested. In mouse blood cells, the extract was antigenotoxic at all concentrations, whereas casearin X was not antimutagenic but was antigenotoxic at all concentrations. We conclude that C. sylvestris ethanolic extract and casearin X protect DNA from damage induced by airborne pollutants from sugarcane burning. -- Highlights: ► We assessed DNA protection of C. sylvestris ethanolic extract. ► We assessed DNA protection of casearin X. ► We used Tradescantia pallida micronucleus test as screening. ► We used comet assay and micronucleus test in mice. ► The compounds protected DNA against sugar cane burning pollutants.

  12. Apoptosis-induced cell death due to oleanolic acid in HaCaT keratinocyte cells--a proof-of-principle approach for chemopreventive drug development.

    Science.gov (United States)

    George, V Cijo; Kumar, D R Naveen; Suresh, P K; Kumar, R Ashok

    2012-01-01

    Oleanolic acid (OA) is a naturally occurring triterpenoid in food materials and is a component of the leaves and roots of Olea europaea, Viscum album L., Aralia chinensis L. and more than 120 other plant species. There are several reports validating its antitumor activity against different cancer cells apart from its hepatoprotective activity. However, antitumor activity against skin cancer has not been studied well thus far. Hence the present study of effects of OA against HaCaT (immortalized keratinocyte) cells--a cell-based epithelial model system for toxicity/ethnopharmacology-based studies--was conducted. Radical scavenging activity (DPPH·) and FRAP were determined spectrophotometrically. Proliferation was assessed by XTT assay at 24, 48 and 72 hrs with exposure to various concentrations (12.5-200 μM) of OA. Apoptotic induction potential of OA was demonstrated using a cellular DNA fragmentation ELISA method. Morphological studies were also carried out to elucidate its antitumor potential. The results revealed that OA induces apoptosis by altering cellular morphology as well as DNA integrity in HaCaT cells in a dose-dependent manner, with comparatively low cytotoxicity. The moderate toxicity observed in HaCaT cells, with induction of apoptosis, possibly suggests greater involvement of programmed-cell death-mediated mechanisms. We conclude that OA has relatively low toxicity and has the potential to induce apoptosis in HaCaT cells and hence provides a substantial and sound scientific basis for further validation studies. PMID:22901164

  13. Proton-Induced X-ray Emission (PIXE Analysis and DNA-chain Break study in rat hepatocarcinogenesis: A possible chemopreventive role by combined supplementation of vanadium and beta-carotene

    Directory of Open Access Journals (Sweden)

    Kanjilal NB

    2005-05-01

    Full Text Available Abstract Combined effect of vanadium and beta-carotene on rat liver DNA-chain break and Proton induced X-ray emission (PIXE analysis was studied during a necrogenic dose (200 mg/kg of body weight of Diethyl Nitrosamine (DENA induced rat liver carcinogenesis. Morphological and histopathological changes were observed as an end point biomarker. Supplementation of vanadium (0.5 ppm ad libitum in drinking water and beta-carotene in the basal diet (120 mg/Kg of body weight were performed four weeks before DENA treatment and continued till the end of the experiment (16 weeks. PIXE analysis revealed the restoration of near normal value of zinc, copper, and iron, which were substantially altered when compared to carcinogen treated groups. Supplementation of both vanadium and beta-carotene four weeks before DENA injection was found to offer significant (64.73%, P

  14. The proteosome inhibitor MG132 attenuates Retinoic Acid Receptor trans-activation and enhances trans-repression of Nuclear Factor κB. Potential relevance to chemo-preventive interventions with retinoids

    Directory of Open Access Journals (Sweden)

    Rosier Randy N

    2004-03-01

    Full Text Available Abstract Background Nuclear factor kappa B (NFκB is a pro-malignant transcription factor with reciprocal effects on pro-metastatic and anti-metastatic gene expression. Interestingly, NFκB blockade results in the reciprocal induction of retinoic acid receptors (RARs. Given the established property of RARs as negative regulators of malignant progression, we postulated that reciprocal interactions between NFκB and RARs constitute a signaling module in metastatic gene expression and malignant progression. Using Line 1 tumor cells as a model for signal regulation of metastatic gene expression, we investigated the reciprocal interactions between NFκB and RARs in response to the pan-RAR agonist, all-trans retinoic acid (at-RA and the pan-RAR antagonist, AGN193109. Results At-RA [0.1–1 μM] dose-dependently activated RAR and coordinately trans-repressed NFκB, while AGN193109 [1–10 μM] dose-dependently antagonized the effects of at-RA. At-RA and AGN193109 reciprocally regulate pro-metastatic matrix metalloprotease 9 (MMP 9 and its endogenous inhibitor, the tissue inhibitor of metalloprotease 1 (TIMP 1, in a manner consistent with the putative roles of NFκB and RAR in malignant progression. Activation of RAR concurs with its ubiquitination and proteosomal degradation. Accordingly, the proteosome inhibitor, MG132 [5 μM], blocked RAR degradation, quelled RAR trans-activation and enhanced RAR trans-repression of NFκB. Conclusion We conclude that reciprocal interactions between NFκB and RARs constitute a signaling module in metastatic gene expression and malignant progression and propose that the dissociative effect of proteosome inhibitors could be harnessed towards enhancing the anticancer activity of retinoids.

  15. Chemopreventive effect of cactus (Opuntia humifusa) extracts: radical scavenging activity, pro-apoptosis, and anti-inflammatory effect in human colon (SW480) and breast cancer (MCF7) cells.

    Science.gov (United States)

    Kim, Jinhee; Jho, Kwang Hyun; Choi, Young Hee; Nam, Sang-Yong

    2013-04-30

    Cactus (Opuntia spp) is widely cultivated as a vegetable, fruit, and forage crop and has been used in traditional medicine in American Indian, Mexican, and Korean cultures. Accumulative evidence from both in vitro and in vivo studies using cacti suggests their biological and pharmacological activities, such as their anti-cancer and anti-inflammatory roles in different cancer cells. In this study, the Opuntia humifusa stem (OHS) was extracted with different solvents and screened for radical scavenging activity using 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS˙(+)) and 1,1-diphenyl-2-picryl hydrazyl (DPPH). In addition, the total phenolic and flavonoid contents of each extract were analyzed using the Folin-Ciocalteu method and high performance liquid chromatography, respectively. Further, the cacti's bioactive fractions were evaluated for cell cytotoxicity and to understand their mechanism of action on human colon cancer (SW480) and breast cancer (MCF7) cells. An ethyl acetate (EtOAc) extract exhibited the highest cytotoxicity and resulted in an up-regulated expression of the pro-apoptotic protein Bax (bcl-2 associated X protein) and a down-regulated expression of the anti-apoptotic protein Bcl2 in both SW480 and MCF7 cells. The apoptosis was mediated through activation of caspase 8, 9, and 3/7 activities as well as PARP cleavage in SW480 cells, while the same extract activated only a caspase 9 activity in MCF7 cells. Furthermore, incubation of cells with the EtOAc extract down-regulated the expression of inflammatory molecules such as cyclooxygenase-2 (COX2) and inducible nitric oxide synthase (iNOS) in SW480 cells but not in MCF7 cells. Taken together, these results suggest that SW480 colon cancer cells are more susceptible to bioactive compounds present in OHS and may have potential in the prevention of cancer through modulation of apoptosis markers and inhibition of inflammatory pathways. PMID:23435602

  16. Chemoprevention of mammary, cervix and nervous system carcinogenesis in animals using cultured Panax ginseng drugs and preliminary clinical trials in patients with precancerous lesions of the esophagus and endometrium.

    OpenAIRE

    V.G. Bespalov; Alexandrov, V A; Limarenko, A Y; Voytenkov, B O; Okulov, V B; Kabulov, M K; Peresunko, A. P.; Slepyan, L I; Davydov, V V

    2001-01-01

    The anticarcinogenic effects and mechanisms of the biotechnological drugs of Panax ginseng C.A. Meyer cultivated in Russia, bioginseng, panaxel and panaxel- 5, were studied. Bioginseng was produced from a tissue culture of ginseng root cultured on standard medium, whereas panaxel and panaxel-5 were produced from ginseng tissue root cultures using standard mediums enriched with 2-carboxyethylgermanium sesquioxide and 1-hydroxygermatran-monohydrate respectively. All three ginseng drugs inhibite...

  17. Concomitant chemopreventive and antibacterial effects of some Iranian plants from the genus Cousinia (Asteraceae Efeitos quimiopreventivo e antibacteriano concomintantes de algumas plantas iranianas do gênero Cousinia (Asteraceae

    Directory of Open Access Journals (Sweden)

    Ahmad Reza Shahverdi

    2007-09-01

    Full Text Available During the past several years, various species of Cousinia (Asteraceae have been authenticated in Iran. However, data concerning their biological activities remain limited. The main purpose of this research was to assess potential cytotoxicity and matrix metalloproteinases (MMP inhibitory effects of seven ethanol extracts of Cousinia using a cell line model (Fibrosarcoma-WEHI 164. We further investigated the antibacterial activity of these Cousinia ethanol extracts, using disk diffusion method. Among the ethanol extracts, the total extract of C. sulabadensis elicited significant inhibition of MMP activity in a dose-response fashion (49.2 ± 0.51, p Durante os últimos anos, várias espécies de Cousinia (Asteraceae têm sido identificadas no Irã. No entanto, dados acerca de suas atividades biológicas permanecem limitados. O principal propósito desta pesquisa foi avaliar a potencial citotoxidade e os efeitos inibitórios de metaloproteinases da matriz (MMP de sete extratos etanólicos de Cousinia utilizando um modelo de linhagem celular (Fibrosarcoma-WEHI 164. Além disso, investigamos a atividade antibacteriana destes extratos etanólicos de Cousinia, utilizando o método de difusão em disco. Dentre os extratos etanólicos, o extrato total de C. sulabadensis promoveu inibição significativa da atividade de MMP de maneira dose-resposta (49,2 ± 0,51, p < 0,05. Todavia, este extrato exibiu o menor efeito de citotoxicidade em todas as concentrações testadas. A concentração necessária para produzir uma taxa de 50% de morte celular (IC50 com C. shulabadensis foi 304,5 ± 0,61 µg/mL. A IC50 calculada para a citotoxicidade dos outros extratos de espécies de Cousinia situou-se entre 18,4 ± 0,59 e 87,9 ± 0,58 µg/mL. A maior atividade antibacteriana foi observada para o extrato total de Cousinia phyllocephala. Em conclusão, este estudo corrobora que espécies de Cousinia mostram uma notável inibição da atividade de metaloproteinases da matriz. Os concomitantes efeitos inibitórios de MMP e baixa citotoxicidade observados em C. sulabadensis devem direcionar este extrato para futuros estudos de potenciais fitoterápicos anti-invasivos.

  18. Proton-Induced X-ray Emission (PIXE) Analysis and DNA-chain Break study in rat hepatocarcinogenesis: A possible chemopreventive role by combined supplementation of vanadium and beta-carotene

    OpenAIRE

    Kanjilal NB; Doloi Manika; Vijayan V; Kulkarni Indira; Mukherjee Sutapa; Chattopadhyay Mitali; Chatterjee Malay

    2005-01-01

    Abstract Combined effect of vanadium and beta-carotene on rat liver DNA-chain break and Proton induced X-ray emission (PIXE) analysis was studied during a necrogenic dose (200 mg/kg of body weight) of Diethyl Nitrosamine (DENA) induced rat liver carcinogenesis. Morphological and histopathological changes were observed as an end point biomarker. Supplementation of vanadium (0.5 ppm ad libitum) in drinking water and beta-carotene in the basal diet (120 mg/Kg of body weight) were performed four ...

  19. Chemoprevention effect of Rosiglitazone on the experimental colon cancer in rat%罗格列酮对实验性大鼠结肠癌的化学预防作用

    Institute of Scientific and Technical Information of China (English)

    吴柯; 何百成; 周岐新

    2012-01-01

    AIM: To investigate the anti-colon cancer effects of rosiglitazone and possible relationship with COX-2. METHODS: Wistar rat colon cancer model was induced by 1 - 2 dimeth-ylhydrazine (DMH) (40 mg/kg s. C. ) + 1% dex-tran sodium sulfate solution (DSS) (freely drinking). All rats were randomly divided into 3 groups:control(DMH + DSS + solvant) , rosiglitazone ( Ros ) ( DMH + DSS + Ros 0. 75 mg · kg-1 · d-1 ) , meloxicam ( Mel ) : (DMH + DSS + Mel 1. 35 mg · kg-1 · d-1). The drugs were given orally once a day for 5 day per week. The body weight, the number of colon ACFs, the incidence and number of colon cancer in rats, as well as the morphological changes of rat colon tissues were evaluated. Human colon cancer Lovo cell line was treated by either Ros or Mel in various concentrations (10-6, 10-5,10-4, 10-3 mol/ L) for 6 h,12 h and 24 h,respectively, and the cell growth was assayed by MTT method. Western blot were used to evaluate the protein expressions of COX-2 from Lovo cells treated with Ros. RESULTS: Ros significantly improved the dyscrasia induced by DMH + DSS, the both of body weight and general condition were better than those of control group. Ros also significantly inhibited ACF and colon cancer incidence in the rats treated by DMH + DSS for 10 weeks or 20 weeks, which was similar to that of Mel. Ros inhibited the proliferation of Lovo cells in concentration- and time-dependent manners, and the IC50 values were significantly smaller than that of Mel at 6 h,12 h, and 24 h after Lovo cells were treated by either Ros or Mel. Ros also concentration-dependently decreased expressions of COX-2 protein. CONCLUSION: Ros can inhibit ACF and tumor formation induced by DMH + DSS, and decrease the Lovo cell proliferation index. The anti-tumor effects of Ros may involve in an unknown pathway through which the expressions of COX-2 were inhibited.%目的:观察罗格列酮对实验性结肠癌的化学预防作用及其与环氧化酶-2 (COX-2)表达的关系.方法:以二甲肼( 1-2 dimethylhydrazine,DMH) 40 mg/kg皮下注射+1%葡聚糖硫酸钠(dextran sodium sulfate,DSS)水溶液饮用诱导形成大鼠结肠癌模型,观察罗格列酮(0.75 mg· kg-1·d-1,1周5d)和美洛昔康(1.35 mg· kg-1·d-1,1周5 d)灌服、连续16周对大鼠体重、异常隐窝灶(ACF)和结肠癌发生率的影响.采用四甲基谷氮蓝法(MTT)研究罗格列酮和美洛昔康抑制培养的人结肠癌Lovo细胞增殖的量-效和时-效关系;用Western Blot法检测罗格列酮组细胞COX-2蛋白表达水平.结果:与模型组相比,罗格列酮明显改善DMH+DSS诱癌过程中大鼠的恶液质状态并阻遏体重减轻,显著减少实验第10周大鼠结肠ACF数和明显降低结肠癌的发生率;其作用与美洛昔康组相似.罗格列酮呈浓度和时间依赖性明显抑制Lovo细胞增殖,其作用6h、12h和24 h的IC50均显著小于美洛昔康.罗格列酮呈浓度依赖性降低Lovo细胞中COX-2蛋白表达.结论:罗格列酮能抑制DMH和DSS联合使用诱导大鼠早期ACF的形成和结肠癌发生,其作用途径可能与抑制COX-2表达有关.

  20. 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.

  1. Natural compounds as anticancer agents: Experimental evidence

    OpenAIRE

    Wang, Jiao; Jiang, Yang-Fu

    2012-01-01

    Cancer prevention research has drawn much attention worldwide. It is believed that some types of cancer can be prevented by following a healthy life style. Cancer chemoprevention by either natural or synthetic agents is a promising route towards lowering cancer incidence. In recent years, the concept of cancer chemoprevention has evolved greatly. Experimental studies in animal models demonstrate that the reversal or suppression of premalignant lesions by chemopreventive agents is achievable. ...

  2. 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....

  3. Chemotherapeutic prevention studies of prostate cancer

    DEFF Research Database (Denmark)

    Djavan, Bob; Zlotta, Alexandre; Schulman, Claude; Teillac, Pierre; Iversen, Peter; Boccon Gibod, Laurent; Bartsch, Georg; Marberger, Michael

    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....

  4. Altered membrane lipid dynamics and chemoprevention by non-steroidal anti inflammatory drugs during colon carcinogenesis Alteración de la dinámica de los lípidos de membrana y quimioprevención mediante los fármacos antiinflamatorios no esteroideos en la carcinogénesis de colon

    OpenAIRE

    S. Singh Kanwar; V. Vaish; S. Nath Sanya

    2011-01-01

    The present work focuses on the anti-neoplastic role of non steroidal anti-inflammatory drugs (NSAIDs) in modulating the biophysical parameters of the colonic membranes in 1,2-dimethylhydrazine dihydrochloride (DMH) induced carcinogenesis. The steady-state fluorescence polarization technique was applied to assess membrane fluidity, membrane polarity and lipid phase states. The decline in cholesterol content, biosynthesis and cholesterol: phospholipids ratio with DMH treatment indicates more f...

  5. Chemopreventive effect of Dongju compound against DMBA / Croton Oil induced skin papillomagenesis in mice%复方冬菊抑制DMBA/巴豆油诱导小鼠皮肤乳头状瘤生成的作用观察

    Institute of Scientific and Technical Information of China (English)

    沈雪敏; 姚辉; 周曾同

    2009-01-01

    目的:应用小鼠皮肤乳头状瘤生成模型,验证复方冬菊对化学致癌剂的对抗作用.方法:ICR雄性小鼠60只,随机分成模型组、复方冬菊给药组和阳性药物(增生平)对照组.小鼠背部脱毛,涂抹致癌剂DMBA/巴豆油至实验结束.12周后清点小鼠背部乳头状瘤数,以各组荷瘤动物占该组存活动物数的百分比值计算肿瘤发生率,用各组小鼠乳头瘤发生总数和该组存活小鼠数计算每鼠平均荷瘤数.比较复方冬菊给药组、阳性药物对照组和模型组肿瘤发生情况,评价药物对肿瘤生长的抑制作用.结果:实验第6周,模型组小鼠背部开始出现乳头状瘤,每鼠平均荷瘤数1.4个;复方冬菊给药组于第8周开始出现肿瘤,复方冬菊给药组和阳性药物对照组每鼠平均荷瘤数较模型组下降,分别为0.25个和0.5个,抑瘤率分别达到82.1%和64.3%.结论:复方冬菊能在一定程度上推迟肿瘤发生时间,减少小鼠皮肤乳头状瘤的发生.可见,复方冬菊对化学致癌剂有一定的对抗作用.

  6. Potential chemoprevention of LPS-stimulated nitric oxide and prostaglandin E₂ production by α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranosyl-3-indolecarbonate in BV2 microglial cells through suppression of the ROS/PI3K/Akt/NF-κB pathway.

    Science.gov (United States)

    Dilshara, Matharage Gayani; Lee, Kyoung-Tae; Choi, Yung Hyun; Moon, Dong-Oh; Lee, Hak-Ju; Yun, Sung Gyu; Kim, Gi-Young

    2014-02-01

    α-l-Rhamnopyranosyl-(1→6)-β-d-glucopyranosyl-3-indolecarbonate (RG3I) is a chemical constituent isolated from the commonly used Asian traditional medicinal plant, Clematis mandshurica; however, no studies have been reported on its anti-inflammatory properties. In the present study, we found that RG3I attenuates the lipopolysaccharide (LPS)-induced DNA-binding activity of nuclear factor-κB (NF-κB) via the dephosphorylation of PI3K/Akt in BV2 microglial cells, leading to a suppression of nitric oxide (NO) and prostaglandin E2 (PGE2) production, along with that of their regulatory genes, inducible NO synthase (iNOS) and cyclooxygenase-2 (Cox-2). Further, the PI3K/Akt inhibitor, LY294002 diminished the expression of LPS-stimulated iNOS and COX-2 genes by suppressing NF-κB activity. Moreover, RG3I significantly inhibited LPS-induced reactive oxygen species (ROS) generation similar to the ROS inhibitors, N-acetylcysteine (NAC) and glutathione (GSH). Notably, NAC and GSH abolished the LPS-induced expression of iNOS and Cox-2 in BV2 microglial cells by inhibiting NF-κB activity. Taken together, our data indicate that RG3I suppresses the production of proinflammatory mediators such as NO and PGE2 as well as their regulatory genes in LPS-stimulated BV2 microglial cells by inhibiting the PI3K/Akt- and ROS-dependent NF-κB signaling pathway, suggesting that RG3I may be a good candidate to regulate LPS-induced inflammatory response. PMID:24486459

  7. Epigenetic potential of resveratrol and analogs in preclinical models of prostate cancer

    Science.gov (United States)

    Prostate cancer is affected by lifestyle, particularly diet. Dietary polyphenols such as resveratrol possess anticancer properties and, therefore, chemopreventive and therapeutic potentials. Resveratrol has pleiotropic effect exerting its biological activity through multiple pathways and targets ass...

  8. Metabolomic profile of response to supplementation with β-carotene in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study123

    OpenAIRE

    Mondul, Alison M.; Sampson, Joshua N.; Moore, Steven C.; Weinstein, Stephanie J.; Evans, Anne M.; Karoly, Edward D; Virtamo, Jarmo; Albanes, Demetrius

    2013-01-01

    Background: Two chemoprevention trials found that supplementation with β-carotene increased the risk of lung cancer and overall mortality. The biologic basis of these findings remains poorly understood.

  9. Role of retinoic receptors in lung carcinogenesis

    Directory of Open Access Journals (Sweden)

    Renyi-Vamos Ferenc

    2008-07-01

    Full Text Available Abstract Several in vitro and in vivo studies have examined the positive and negative effects of retinoids (vitamin A analogs in premalignant and malignant lesions. Retinoids have been used as chemopreventive and anticancer agents because of their pleiotropic regulator function in cell differentiation, growth, proliferation and apoptosis through interaction with two types of nuclear receptors: retinoic acid receptors and retinoid X receptors. Recent investigations have gradually elucidated the function of retinoids and their signaling pathways and may explain the failure of earlier chemopreventive studies. In this review we have compiled basic and recent knowledge regarding the role of retinoid receptors in lung carcinogenesis. Sensitive and appropriate biological tools are necessary for screening the risk population and monitoring the efficacy of chemoprevention. Investigation of retinoid receptors is important and may contribute to the establishment of new strategies in chemoprevention for high-risk patients and in the treatment of lung cancer.

  10. Anticancer Effect of Rutin Isolated from the Methanolic Extract of Triticum aestivum Straw in Mice

    OpenAIRE

    Savita Dixit

    2014-01-01

    Rutin is the bioactive flavanoid isolated from the straw part of Triticum aestivum and possess various pharmacological applications. The aim of this study is to evaluate the chemopreventive potential of rutin in an experimental skin carcinogenesis mice model system. Skin tumor was induced by topical application of 7,12-dimethyl benz(a) anthracene (DMBA) and promoted by croton oil in Swiss albino mice. To assess the chemopreventive potential of rutin, it was orally administered at a concentrat...

  11. Retinoids, breast cancer and NK cells.

    OpenAIRE

    Villa, M. L.; Ferrario, E; Trabattoni, D.; Formelli, F.; G. De Palo; Magni, A.; Veronesi, U; Clerici, E.

    1993-01-01

    N-(4-hydroxyphenyl) retinamide (4-HPR) is a synthetic retinoid which reduces the incidence of experimental tumours in animals and has been chosen for its weak toxicity to be tested as a chemopreventive agent in humans. The mechanism of antineoplastic action is still unknown but a possible immunoenhancing effect may be postulated. We investigated the NK activity of PBMC from a group of women treated with 4-HPR as a part of a large scale randomised phase III trial on chemoprevention of contrala...

  12. Retinoid X Receptor Agonists Upregulate Genes Responsible for the Biosynthesis of All-Trans-Retinoic Acid in Human Epidermis

    OpenAIRE

    Wu, Lizhi; Chaudhary, Sandeep C.; Atigadda, Venkatram R.; Belyaeva, Olga V.; Steven R Harville; Elmets, Craig A.; Muccio, Donald D.; Athar, Mohammad; Kedishvili, Natalia Y.

    2016-01-01

    UAB30 is an RXR selective agonist that has been shown to have potential cancer chemopreventive properties. Due to high efficacy and low toxicity, it is currently being evaluated in human Phase I clinical trials by the National Cancer Institute. While UAB30 shows promise as a low toxicity chemopreventive drug, the mechanism of its action is not well understood. In this study, we investigated the effects of UAB30 on gene expression in human organotypic skin raft cultures and mouse epidermis. Th...

  13. Opposing effects of androgen deprivation and targeted therapy on prostate cancer prevention

    OpenAIRE

    Jia, Shidong; Gao, Xueliang; Lee, Sang Hyun; Maira, Sauveur-Michel; Wu, Xiaoqiu; Stack, Edward C.; Signoretti, Sabina; Loda, Massimo; Zhao, Jean J.; Roberts, Thomas M.

    2012-01-01

    Prostate cancer is an ideal target for chemoprevention. To date, chemoprevention clinical trials with 5α-reductase inhibitors (5-ARI) have yielded encouraging yet ultimately confounding results. Using a pre-clinical mouse model of high-grade prostatic intraepithelial neoplasia (HG-PIN) induced by PTEN loss, we observed unprecedented deteriorating effects of androgen deprivation, where surgical castration or MDV3100 treatment accelerated disease progression of the otherwise stable HG-PIN to in...

  14. Oral Cancer Chernoprevention: Current Status and Future Direction.

    Science.gov (United States)

    Messadi, Diana V; Sato, Kazumichi

    2016-02-01

    The aim of this study is to review the current status of cancer chemoprevention and its effectiveness in treatment of oral premalignant lesions and prevention of their progression to oral cancer. The challenges encountered in the different oral cancer chemoprevention clinical trials, including lack of surrogate endpoints, reversal of histologic premalignant changes as study endpoints, tobacco use, human papillomavirus, delivery system, adverse effects and risk of bias in clinical studies, are presented. PMID:26930753

  15. Methods to Predict and Lower the Risk of Prostate Cancer

    OpenAIRE

    Barbara Ercole; Dipen J Parekh

    2011-01-01

    Chemoprevention for prostate cancer (PCa) continues to generate interest from both physicians and the patient population. The goal of chemoprevention is to stop the malignant transformation of prostate cells into cancer. Multiple studies on different substances ranging from supplements to medical therapy have been undertaken. Thus far, only the studies on 5α-reductase inhibitors (the Prostate Cancer Prevention Trial [PCPT] and Reduction by Dutasteride of Prostate Cancer Events [REDUCE] trial)...

  16. Total isothiocyanate yield from raw cruciferous vegetables commonly consumed in the United States

    OpenAIRE

    Tang, Li; Paonessa, Joseph D.; Zhang, Yuesheng; Ambrosone, Christine B; McCann, Susan E.

    2013-01-01

    Dietary isothiocyanates are a group of promising chemopreventive agents obtained primarily from cruciferous vegetables. Due to their potent chemopreventive and/or anti-cancer activities, there is a growing interest in assessing dietary isothiocyanate exposure and its impact on human health. Using the HPLC-based cyclocondensation assay, the current study measured total isothiocyanate yield from raw cruciferous vegetables. A total of 73 samples comprising nine types of cruciferous vegetables we...

  17. Selenoproteins reduce susceptibility to DMBA-induced mammary carcinogenesis

    OpenAIRE

    Hudson, Tamaro S.; Carlson, Bradley A.; Hoeneroff, Mark J.; Young, Heather A.; Sordillo, Lorraine; Muller, William J.; Hatfield, Dolph L.; Green, Jeffrey E.

    2012-01-01

    Selenium is an essential micronutrient in the diet of humans and other mammals. Based largely on animal studies and epidemiological evidence, selenium is purported to be a promising cancer chemopreventive agent. However, the biological mechanisms by which chemopreventive activity takes place are poorly understood. It remains unclear whether selenium acts in its elemental form, through incorporation into organic compounds, through selenoproteins or any combination of these. The purpose of this...

  18. Nanochemoprevention by Bioactive Food Components: A Perspective

    OpenAIRE

    Siddiqui, Imtiaz A.; Mukhtar, Hasan

    2010-01-01

    Chemoprevention through the use of bioactive food components is a practical approach for cancer control. Despite abundant efficacy data under preclinical settings, this strategy has resulted in limited success for human cancer control. Amongst many reasons, inefficient systemic delivery and bioavailability of promising chemopreventive agents are considered to significantly contribute to such a disconnect. We recently introduced a novel concept in which we utilized nanotechnology for enhancing...

  19. Manipolazione del metabolismo degli xenobiotici da frutta convenzionale ed attività chemiopreventiva

    OpenAIRE

    Bonamassa, Barbara

    2010-01-01

    A reduced cancer risk associated with fruit and vegetable phytochemicals initially dictated chemopreventive approaches focused on specific green variety consumption or even single nutrient supplementations. However, these strategies not only failed to provide any health benefits but gave rise to detrimental effects. In parallel, public-health chemoprevention programmes were developed in the USA and Europe to increase whole vegetable consumption. Among these, the National Cancer Institute (NCI...

  20. Targeting Nrf2-Mediated Gene Transcription by Triterpenoids and Their Derivatives

    OpenAIRE

    Loboda, Agnieszka; Rojczyk-Golebiewska, Ewa; Bednarczyk-Cwynar, Barbara; Lucjusz, Zaprutko; Jozkowicz, Alicja; Dulak, Jozef

    2012-01-01

    Chemoprevention represents a strategy designed to protect cells or tissues against various carcinogens and carcinogenic metabolites derived from exogenous or endogenous sources. Recent studies indicate that plant-derived triterpenoids, like oleanolic acid, may exert cytoprotective functions via regulation of the activity of different transcription factors. The chemopreventive effects may be mediated through induction of the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription fact...

  1. Plants Against Cancer: A Review on Natural Phytochemicals in Preventing and Treating Cancers and Their Druggability

    OpenAIRE

    Wang, Hu; Khor, Tin Oo; Shu, Limin; Su, Zhengyuen; Fuentes, Francisco; Lee, Jong-Hun; Kong, Ah-Ng Tony

    2012-01-01

    Cancer remains to be one of the leading causes of death in the United States and around the world. The advent of modern drug-targeted therapies has undeniably improved cancer patients’ cares. However, advanced metastasized cancer remains untreatable. Hence, continued searching for a safer and more effective chemoprevention and treatment is clearly needed for the improvement of the efficiency and to lower the treatment cost for cancer care. Cancer chemoprevention with natural phytochemical com...

  2. Breast cancer prevention with anti-estrogens: review of the current evidence and future directions.

    Science.gov (United States)

    Mallick, Supriya; Benson, Rony; Julka, P K

    2016-03-01

    There is a potential for reducing the incidence of breast cancer by modifying or changing the reversible risk factors like dietary modifications, modifications in the sedentary life habits, etc. One of such methods which has gained popularity now is chemoprevention. Many agents have been evaluated in the chemoprevention setting in females with increased risk of breast cancers. Metformin, NSAIDS, Bisphosphonates, and statins were evaluated by various investigators with variable results. One of the agents that have been proven to be beneficial in this setting is the anti-estrogens. A major disadvantage of chemoprevention is that unlike prophylactic mastectomy it can never reduce the risk to near zero although it reduces the risk significantly. Another issue is the compliance as chemoprevention with anti-estrogens will need to be continued for 5 years while surgery is a one-time procedure. Another disadvantage is the possible side effects peculiar to each drug used which may not be a significant concern in prophylactic mastectomy group. All these factors must also be kept in mind and properly explained to the patient before starting chemoprevention using anti-estrogens. Here in this review we intend to look into the large randomized controlled trials to quantify the present status of chemoprevention with anti-estrogens. PMID:26439380

  3. Impact of nanotechnology on the delivery of natural products for cancer prevention and therapy.

    Science.gov (United States)

    Siddiqui, Imtiaz A; Sanna, Vanna

    2016-06-01

    Chemoprevention of human cancer by dietary products is a practical approach of cancer control, especially when chemoprevention is involved during the early stages of the carcinogenesis process. Research over the last few decades has clearly demonstrated the efficacy of dietary products for chemoprevention in cell culture and preclinical animal model systems. However, these in vitro and in vivo effects have not been able to be translated to bedside for clinical use. Among many reasons, inefficient systemic delivery and bioavailability of promising chemopreventive agents are considered to significantly contribute to such a disconnection. Since its advent in the field of cancer, nanotechnology has provided researchers with expertise to explore new avenues for diagnosis, prevention, and therapy of the disease. In a similar trait, we introduced a novel concept in which nanotechnology was utilized for enhancing the outcome of chemoprevention (Cancer Res. 2009; 69:1712-1716). This idea, which we termed as 'nanochemoprevention', was exploited by several laboratories and has now become an advancing field in chemoprevention research. This review summarizes some of these applications of nanotechnology in medicine, particularly focused on controlled and sustained release of bioactive compounds with emphasis on current and future utilization of nanochemoprevention for prevention and therapy of cancer. PMID:26935239

  4. 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

  5. Chemopreventive activity of phenylalanine against damage mutagenic prompted by the acute administration of cyclophosphamide in pregnant and non-pregnant mice using the micronucleus test Atividade quimiopreventiva da fenilalanina contra danos mutagênicos pela administração aguda de ciclofosfamida em ratas grávidas e não grávidas, utilizando o teste do micronúcleo

    OpenAIRE

    Mariana de Oliveira Mauro; João Renato Pesarini; Priscila Lumi Ishii; Ariane Fernanda da Silva; Rodrigo Juliano Oliveira

    2010-01-01

    This study aimed to evaluate the quimiopreventive ability of phenylalanine. We used pregnant and non-pregnant female mice divided into the following groups: G1-PBS, (0.1 mL/kg b.w); G2, cyclophosphamide (35 mg/kg p.c.-i.p.); G3 and G4, phenylalanine (150 and 300 mg/kg b.w respectively-v.o.) and G5 and G6, association between the two doses of phenylalanine and cyclophosphamide, respectively. The peripheral blood samples were taken at T0, before the administration of any drug test and / or vehi...

  6. Tamoxifen and curcumin binding to serum albumin. Spectroscopic study

    Science.gov (United States)

    Maciążek-Jurczyk, M.; Maliszewska, M.; Pożycka, J.; Równicka-Zubik, J.; Góra, A.; Sułkowska, A.

    2013-07-01

    Tamoxifen (TMX) is widely used for the breast cancer treatment and is known as chemopreventive agent. Curcumin (CUR) is natural phenolic compound with broad spectrum of biological activity e.g. anti-inflammatory, antimicrobial, antiviral, antifungal and chemopreventive. Combination of tamoxifen and curcumin could be more effective with lower toxicity than each agent alone in use for the treatment or chemoprevention of breast cancer. Binding of drugs to serum albumin is an important factor, which determines toxicity and therapeutic dosage of the drugs. When two drugs are administered together the competition between them for the binding site on albumin can result in a decrease in bound fraction and an increase in the concentration of free biologically active fraction of drug.

  7. 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.

  8. A component of green tea (-)-epigallocatechin-3-gallate, promotes apoptosis in T24 human bladder cancer cells via modulation of the PI3K/Akt pathway and Bcl-2 family proteins

    International Nuclear Information System (INIS)

    Bladder cancer is the fourth most common cancer in men and ninth most common in women. It has a protracted course of progression and is thus an ideal candidate for chemoprevention strategies and trials. This study was conducted to evaluate the chemopreventive/antiproliferative potential of (-)-epigallocatechin gallate (EGCG, the major phytochemical in green tea) against bladder cancer and its mechanism of action. Using the T24 human bladder cancer cell line, we found that EGCG treatment caused dose- and time-dependent inhibition of cellular proliferation and cell viability, and induced apoptosis. Mechanistically, EGCG inhibits phosphatidylinositol 3'-kinase/Akt activation that, in turn, results in modulation of Bcl-2 family proteins, leading to enhanced apoptosis of T24 cells. These findings suggest that EGCG may be an important chemoprevention agent for the management of bladder cancer

  9. Instructions for Applying | Division of Cancer Prevention

    Science.gov (United States)

    This is NOT a grant application - if successful, funds will not be transferred to your institution to support your project. Rather, this is an application to access the scientific capabilities and resources of the NCI with the goal of moving promising cancer chemopreventive agents into clinical testing. If successful, you will partner with the NCI in developing a drug development pipeline. | Apply to access the scientific capabilities and resources of the NCI with the goal of moving promising cancer chemopreventive agents into clinical testing.

  10. 硒防治癌症的困扰与求变:纳米硒的创新

    Institute of Scientific and Technical Information of China (English)

    张劲松

    2004-01-01

    Selenium is a promising agent for chemoprevention and chemotherapy of cancer. However, present research data indicate the supranutritional dose and even higher level are necessary for better efficacy. These doses approaches toxic dose. The dilemma in selenium argues the exploration of novel selenium form with lower toxicity and higher biological functions is urgent. The long-held opinion is elemental selenium is biological inert. We show that elemental in nano particles has high bioavailability and substantial low toxicity, indicating its promising application in chemoprevention and chemotherapy.

  11. Methods to Predict and Lower the Risk of Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Barbara Ercole

    2011-01-01

    Full Text Available Chemoprevention for prostate cancer (PCa continues to generate interest from both physicians and the patient population. The goal of chemoprevention is to stop the malignant transformation of prostate cells into cancer. Multiple studies on different substances ranging from supplements to medical therapy have been undertaken. Thus far, only the studies on 5α-reductase inhibitors (the Prostate Cancer Prevention Trial [PCPT] and Reduction by Dutasteride of Prostate Cancer Events [REDUCE] trial have demonstrated a reduction in the risk of PCa, while results from the Selenium and Vitamin E Cancer Prevention Trial (SELECT concluded no decreased risk for PCa with selenium or vitamin E.

  12. Antioxidant generation and regeneration in lipid bilayers: the amazing case of lipophilic thiosulfinates and hydrophilic thiols.

    Science.gov (United States)

    Zheng, Feng; Pratt, Derek A

    2013-09-25

    We demonstrate that the garlic-derived chemopreventive agent allicin and the related anamu-derived petivericin are poor radical-trapping antioxidants in lipid bilayers, but that the in situ reaction of a lipophilic analog and a hydrophilic thiol yields an extremely potent radical-trapping antioxidant that can be recycled in the presence of excess thiol. PMID:23938951

  13. Anti-oncogenic perspectives of spices/herbs: A comprehensive review

    OpenAIRE

    Butt, Masood Sadiq; Naz, Ambreen; Sultan, Muhammad Tauseef; Qayyum, Mir Muhammad Nasir

    2013-01-01

    Contemporary nutrition regime has focused the attention of the researchers on phytochemicals enriched spices to mitigate various oncological threats. Numerous chemopreventive strategies against malignancy have been developed considering the anticancer perspectives of allied nutraceutical constituents. Current evidences have proven an inverse association of spices with that of oncological incidences. The high antioxidant activity of spices derived bioactives triggers the free radicals scavengi...

  14. Anti-oncogenic perspectives of spices/herbs

    OpenAIRE

    Butt, Masood Sadiq; Naz, Ambreen; Sultan, Muhammad Tauseef; Qayyum, Mir Muhammad Nasir

    2013-01-01

    Contemporary nutrition regime has focused the attention of the researchers on phytochemicals enriched spices to mitigate various oncological threats. Numerous chemopreventive strategies against malignancy have been developed considering the anticancer perspectives of allied nutraceutical constituents. Current evidences have proven an inverse association of spices with that of oncological incidences. The high antioxidant activity of spices derived bioactives triggers the free radicals scavengi...

  15. Differential effects of resveratrol on androgen-responsive LNCaP human prostrate cancer cells in vitro and in vivo.

    Science.gov (United States)

    Resveratrol is a phytochemical that has been under consideration for use as a prostate cancer chemopreventive agent. However, the efficacy, as well as the mechanisms of action of resveratrol on prostate cancer prevention, remains largely unknown. This study seeks to address these questions and exami...

  16. Pleiotropic effects of the sirtuin inhibitor sirtinol involves concentration-dependent modulation of multiple nuclear receptor-mediated pathways in the androgen-responsive prostate cancer cell LNCaP

    Science.gov (United States)

    Sirtinol, a purported specific inhibitor of the nicotinamide adenine dinucleotide (NAD)-dependent type III histone deacetylase (also known as sirtuin), has been used extensively to identify chemopreventive/chemotherapeutic agents that modulate the activity of this group of enzymes. However, the mole...

  17. Psychological Issues in Cancer Genetics: Current Research and Future Priorities.

    Science.gov (United States)

    Hopwood, Penelope

    1997-01-01

    Data concerning the psychological impact of high risk of cancer are reviewed, including implications of genetic testing, breast screening,and accuracy of women's risk estimates. Work in progress on prophylactic mastectomy and chemoprevention is reviewed. Research on cancer families, and interventions and prevention strategies for high-risk…

  18. Lycopene and Lung Cancer

    Science.gov (United States)

    Although epidemiological studies have shown dietary intake of lycopene is associated with decreased risk of lung cancer, the effect of lycopene on lung carcinogenesis has not been well studied. A better understanding of lycopene metabolism and the mechanistic basis of lycopene chemoprevention must ...

  19. Apo-10'-lycopenoic acid suppresses lung cancer cell growth by activating retinoic acid receptor Beta in vitro, and inhibits lung tumorigenesis in vivo in the A/J mouse model

    Science.gov (United States)

    Lycopene, which has been associated with a lower risk of a variety of cancers including lung cancer, can be cleaved enzymatically at its 9',10'-double bond and converted into apo-10'-lycopenoids both in vivo and in vitro. Here, we evaluated the potential chemopreventive effect of apo-10'-lycopenoic...

  20. Dietary lycopene and tomato extract supplementations inhibit nonalcoholic steatohepatitis-promoted hepatocarcinogenesis in rats

    Science.gov (United States)

    Epidemiological and experimental studies provide supportive evidence that lycopene (LY), a major carotenoid from tomatoes and tomato products, may act as a chemopreventive agent against certain types of cancers. We recently showed that high-fat diet (HFD)-induced nonalcoholic steatohepatitis (NASH) ...

  1. Yerba mate tea and mate saponins prevented azoxymethane-induced inflammation of rat colon through suppression of NF-kB p65ser(311) signaling via IkB-a and GSK-3ß reduced phosphorylation

    Science.gov (United States)

    Yerba mate tea (YMT) has a chemopreventive role in a variety of inflammatory diseases. The objective was to determine the capability of YMT and mate saponins to prevent azoxymethane (AOM)-induced colonic inflammation in rats. YMT (2% dry leaves, w/v, as a source of drinking fluid) (n = 15) and mat...

  2. Assessing the anticancer compounds Se-methylselenocysteine and glucosinolates in Se-biofortified broccoli (brassica oleracea L. var. italica) sprouts and florets

    Science.gov (United States)

    Broccoli (Brassica oleracea L. var. italica) is a rich source of chemopreventive compounds. Here, we evaluated and compared the effect of selenium (Se) treatment on the accumulation of anticancer compound Se-methylselenocysteine (SeMSCys) and glucosinolates in broccoli sprouts and florets. Total Se ...

  3. 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. |

  4. 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...

  5. About the Prostate and Urologic Cancer Research Group | Division of Cancer Prevention

    Science.gov (United States)

    The Prostate and Urologic Cancer Research Group conducts and supports research on prostate and bladder cancers, and new approaches to clinical prevention studies including cancer immunoprevention. The group develops, implements and monitors research efforts in chemoprevention, nutrition, genetic, and immunologic interventions, screening, early detection and other prevention strategies. |

  6. The selenium metabolite methylselenol regulates the expression of ligands that trigger immune activation through the lymphocyte receptor NKG2D

    DEFF Research Database (Denmark)

    Hagemann-Jensen, Michael Henrik; Uhlenbrock, Franziska Katharina; Kehlet, Stephanie; Andresen, Lars; Gabel-Jensen, Charlotte; Ellgaard, Lars; Gammelgaard, Bente; Skov, Søren

    2014-01-01

    For decades Selenium (Se) research has been focused on the identification of active metabolites, which are crucial for Se chemoprevention of cancer. In this context, the metabolite methylselenol (CH3SeH) is known for its action to selectively kill transformed cells through mechanisms that include...

  7. Of the major phenolic acids formed during human microbial fermentation of tea, citrus, and soy flavonoid supplements, only 3,4-dihydroxyphenylacetic acid has antiproliferative activity

    NARCIS (Netherlands)

    Gao, K.; Xu, A.; Krul, C.A.M.; Venema, K.; Liu, Y.; Niu, Y.; Lu, J.; Bensoussan, L.; Seeram, N.P.; Heber, D.; Henning, S.M.

    2006-01-01

    Dietary flavonoids are poorly absorbed from the gastrointestinal tract. Colonic bacteria convert flavonoids into smaller phenolic acids (PA), which can be absorbed into the circulation and may contribute to the chemopreventive activity of the parent compounds. The purpose of our study was to determi

  8. Cafestol: a multi-faced compound kinetics and metabolic effects of cafestol in mice

    NARCIS (Netherlands)

    Cruchten, van S.T.J.

    2010-01-01

    Cafestol and kahweol are two diterpenes present in unfiltered coffees such as Scandinavian-style boiled coffee, French press coffee and espresso. The health effects of cafestol and kahweol can be positive but also potentially harmful. On the one hand cafestol shows chemo-preventive properties, which

  9. Main: 1D6R [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 1D6R 大豆 Soybean Glycine max (L.) Merrill Bowman-Birk Type Proteinase Inhibitor Precursor Glyci ... Warkentin, G.Wenzl, P.Flecker Crystal Structure Of Cancer ... Chemopreventive Bowman-Birk Inhibitor In Ternary C ...

  10. 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...

  11. Special Section: Colorectal Cancer Symptoms, Diagnosis and Treatment

    Science.gov (United States)

    ... two chemopreventive agents—an anti-inflammatory and an experimental compound—are very effective at preventing the recurrence of the lesions that are often a sign of colorectal cancer. The results showed that the treatment was most effective in preventing the recurrence of ...

  12. Butyrate plays differential roles in cellular signaling in cancerous HCT116 and noncancerous NCM460 colon cells

    Science.gov (United States)

    Butyrate, an intestinal microbiota metabolite of dietary fiber, exhibits chemoprevention effects in colon. However, the mechanistic action of butyrate at the cellular level remains to be determined. We hypothesize that butyrate plays differential roles in cancerous and non-cancerous cells through si...

  13. Methylselenol, a selenium metabolite, plays common and different roles in cancerous colon HCT116 cell and noncancerous NCM460 colon cell proliferation

    Science.gov (United States)

    Methylselenol has been hypothesized to be a critical selenium (Se) metabolite for anticancer activity in vivo. To determine differential chemopreventive effects of methylselenol on colon cancer cells versus colon noncancerous cells, colon-cancer-derived HCT-116 cells and noncancerous colonic NCM460 ...

  14. Prolonged sulforaphane treatment activates survival signaling in nontumorigenic NCM460 colon cells but apoptotic signaling in tumorigenic HCT116 colon 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...

  15. Modulation of cigarette smoke-related end-points in mutagenesis and carcinogenesis

    International Nuclear Information System (INIS)

    The epidemic of lung cancer and the increase of other tumours and chronic degenerative diseases associated with tobacco smoking have represented one of the most dramatic catastrophes of the 20th century. The control of this plague is one of the major challenges of preventive medicine for the next decades. The imperative goal is to refrain from smoking. However, chemoprevention by dietary and/or pharmacological agents provides a complementary strategy, which can be targeted not only to current smokers but also to former smokers and passive smokers. This article summarises the results of studies performed in our laboratories during the last 10 years, and provides new data generated in vitro, in experimental animals and in humans. We compared the ability of 63 putative chemopreventive agents to inhibit the bacterial mutagenicity of mainstream cigarette smoke. Modulation by ethanol and the mechanisms involved were also investigated both in vitro and in vivo. Several studies evaluated the effects of dietary chemopreventive agents towards smoke-related intermediate biomarkers in various cells, tissues and organs of rodents. The investigated end-points included metabolic parameters, adducts to haemoglobin, bulky adducts to nuclear DNA, oxidative DNA damage, adducts to mitochondrial DNA, apoptosis, cytogenetic damage in alveolar macrophages, bone marrow and peripheral blood erytrocytes, proliferation markers, and histopathological alterations. The agents tested in vivo included N-acetyl-L-cysteine, 1,2-dithiole-3-thione, oltipraz, phenethyl isothiocyanate, 5,6-benzoflavone, and sulindac. We started applying multigene expression analysis to chemoprevention research, and postulated that an optimal agent should not excessively alter per se the physiological background of gene expression but should be able to attenuate the alterations produced by cigarette smoke or other carcinogens. We are working to develop an animal model for the induction of lung tumours following exposure

  16. Resveratrol: A review of preclinical studies for human cancer prevention

    International Nuclear Information System (INIS)

    The search for novel and effective cancer chemopreventive agents has led to the identification of various naturally occurring compounds one of which is resveratrol (trans-3,4',5-trihydroxystilbene), a phytoalexin derived from the skin of grapes and other fruits. Resveratrol is known to have potent anti-inflammatory and antioxidant effects and to inhibit platelet aggregation and the growth of a variety of cancer cells. Its potential chemopreventive and chemotherapeutic activities have been demonstrated in all three stages of carcinogenesis (initiation, promotion, and progression), in both chemically and UVB-induced skin carcinogenesis in mice, as well as in various murine models of human cancers. Evidence from numerous in vitro and in vivo studies has confirmed its ability to modulate various targets and signaling pathways. This review discusses the current preclinical and mechanistic data available and assesses resveratrol's anticancer effects to support its potential as an anticancer agent in human populations

  17. A proposed staging system and stage-specific interventions for familial adenomatous polyposis

    DEFF Research Database (Denmark)

    Lynch, Patrick M; Morris, Jeffrey S; Wen, Sijin;

    2016-01-01

    scores were within ±1 stage of the mode. Sixty percent agreed on the intervention, and 86% chose an intervention within ±1 level of the mode. CONCLUSIONS: The proposed FAP colon polyposis staging system and stage-specific intervention is based on a high degree of agreement on the part of experts in the...... polyp burden as a sufficient chemoprevention trial treatment endpoint requiring a measure of "clinical-benefit." To develop endpoints for future industry-sponsored chemopreventive trials, the International Society for Gastrointestinal Hereditary Tumors (InSIGHT) developed an FAP staging and intervention...... classification scheme for lower GI tract polyposis. METHODS: Twenty-four colonoscopy or sigmoidoscopy videos were reviewed by 26 clinicians familiar with diagnosis and treatment of FAP. The reviewers independently assigned a stage to a case using the proposed system and chose a stage-specific intervention for...

  18. Mutagenic and antimutagenic effects of aqueous extract of rosemary (Rosmarinus officinalis L.) on meristematic cells of Allium cepa.

    Science.gov (United States)

    Felicidade, I; Lima, J D; Pesarini, J R; Monreal, A C D; Mantovani, M S; Ribeiro, L R; Oliveira, R J

    2014-01-01

    Polyphenolic compounds present in rosemary were found to have antioxidant properties, anticarcinogenic activity, and to increase the detoxification of pro-carcinogens. The aim of the study was to determine the effect the aqueous extract of rosemary (AER) on mutagenicity induced by methylmethane sulfonate in meristematic cells of Allium cepa, as well as to describe its mode of action. Anti-mutagenicity experiments were carried out with 3 different concentrations of AER, which alone showed no mutagenic effects. In antimutagenicity experiments, AER showed chemopreventive activity in cultured meristematic cells of A. cepa against exposure to methylmethane sulfonate. Additionally, post-treatment and simultaneous treatment using pre-incubation protocols were the most effective. Evaluation of different protocols and the percent reduction in DNA indicated bioantimutagenic as well desmutagenic modes of action for AER. AER may be chemopreventive and antimutagenic. PMID:25501210

  19. 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.

  20. Non-steroidal anti-inflammatory drugs in prevention of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Yun Dai; Wei-Hong Wang

    2006-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs)including cyclooxygenase 2 (COX-2) selective inhibitors,are potential agents for the chemoprevention of gastric cancer. Epidemiological and experimental studies have shown that NSAID use is associated with a reduced risk of gastric cancer although many questions remain unanswered such as the optimal dose and duration of treatment. The possible mechanisms for the suppressor effect of NSAIDs on carcinogenesis are the ability to induce apoptosis in epithelial cells and regulation of angiogenesis. Both COX-dependent and COX-independent pathways have a role in the biological activity of NSAIDs. Knowledge of how NSAIDs prevent neoplastic growth will greatly aid the design of better chemopreventive drugs and novel treatments for gastric cancer.

  1. Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in primary melanocytes.

    Science.gov (United States)

    Thompson, Benjamin C; Surjana, Devita; Halliday, Gary M; Damian, Diona L

    2014-07-01

    Cutaneous melanoma is a significant cause of morbidity and mortality. Nicotinamide is a safe, widely available vitamin that reduces the immune suppressive effects of UV, enhances DNA repair in keratinocytes and has shown promise in the chemoprevention of non-melanoma skin cancer. Here, we report the effect of nicotinamide on DNA damage and repair in primary human melanocytes. Nicotinamide significantly enhanced the repair of oxidative DNA damage (8-oxo-7,8-dihydro-2'-deoxyguanosine) and cyclobutane pyrimidine dimers induced by UV exposure. It also enhanced the repair of 8-oxo-7,8-dihydro-2'-deoxyguanosine induced by the culture conditions in unirradiated melanocytes. A significant increase in the percentage of melanocytes undergoing unscheduled but not scheduled DNA synthesis was observed, confirming that nicotinamide enhances DNA repair in human melanocytes. In summary, nicotinamide, by enhancing DNA repair in melanocytes, is a potential agent for the chemoprevention of cutaneous melanoma. PMID:24798949

  2. Chemical profile of mango (Mangifera indica L.) using electrospray ionisation mass spectrometry (ESI-MS).

    Science.gov (United States)

    Oliveira, Bruno G; Costa, Helber B; Ventura, José A; Kondratyuk, Tamara P; Barroso, Maria E S; Correia, Radigya M; Pimentel, Elisângela F; Pinto, Fernanda E; Endringer, Denise C; Romão, Wanderson

    2016-08-01

    Mangifera indica L., mango fruit, is consumed as a dietary supplement with purported health benefits; it is widely used in the food industry. Herein, the chemical profile of the Ubá mango at four distinct maturation stages was evaluated during the process of growth and maturity using negative-ion mode electrospray ionisation Fourier transform ion cyclotron resonance mass spectrometry (ESI(-)FT-ICR MS) and physicochemical characterisation analysis (total titratable acidity (TA), total soluble solids (TSS), TSS/TA ratio, and total polyphenolic content). Primary (organic acids and sugars) and secondary metabolites (polyphenolic compounds) were mostly identified in the third maturation stage, thus indicating the best stage for harvesting and consuming the fruit. In addition, the potential cancer chemoprevention of the secondary metabolites (phenolic extracts obtained from mango samples) was evaluated using the induction of quinone reductase activity, concluding that fruit polyphenols have the potential for cancer chemoprevention. PMID:26988473

  3. The Potential Mechanisms Underlying Aspirin-induced Inhibition of Ovarian Tumor Cell Growth

    Institute of Scientific and Technical Information of China (English)

    Yu LIU; Jin KE; Shi-Quan LIU; Fu-Xiang ZHOU; Cong-Hua XIE; Yun-Feng ZHOU

    2005-01-01

    @@ 1 Introduction Ovarian cancer remains the most lethal disease of the gynecological cancers. Owing to the lack of an effective screening approach combined with inadequate therapeutic approach for advanced disease, fewer than 25% of ovarian cancers are identified at an early curable stage. Thus these make ovarian cancer a strong candidate for chemoprevention. In 2001, Akhmedkhanov et al. demonstrated a 2-3 folds decrease in epithelial ovarian cancer associated with Aspirin use. These epidemiological observations suggest that an improved understanding of the mechanisms by which NSAID may decrease the development of ovarian cancer could lead to improved approaches for chemoprevention of this deadly disease. In this research, we explored the potential mechanism underlying epidemiological observations that ovarian cancer occurs at a lower frequency in women exposed to Aspirin(ASP).

  4. Aspirin and Cancer.

    Science.gov (United States)

    Patrignani, Paola; Patrono, Carlo

    2016-08-30

    The place of aspirin in primary prevention remains controversial, with North American and European organizations issuing contradictory treatment guidelines. More recently, the U.S. Preventive Services Task Force recommended "initiating low-dose aspirin use for the primary prevention of cardiovascular disease (CVD) and colorectal cancer in adults aged 50 to 59 years who have a 10% or greater 10-year CVD risk, are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years." This recommendation reflects increasing evidence for a chemopreventive effect of low-dose aspirin against colorectal (and other) cancer. The intent of this paper is to review the evidence supporting a chemopreventive effect of aspirin, discuss its potential mechanism(s) of action, and provide a conceptual framework for assessing current guidelines in the light of ongoing studies. PMID:27561771

  5. Silymarin nanoparticle prevents paracetamol-induced hepatotoxicity

    OpenAIRE

    Das S; Roy P.; Auddy RG; Mukherjee A

    2011-01-01

    Suvadra Das, Partha Roy, Runa Ghosh Auddy, Arup MukherjeeDepartment of Chemical Technology, University of Calcutta, Kolkata, West Bengal, IndiaAbstract: Silymarin (Sm) is a polyphenolic component extracted from Silybum marianum. It is an antioxidant, traditionally used as an immunostimulant, hepatoprotectant, and dietary supplement. Relatively recently, Sm has proved to be a valuable chemopreventive and a useful antineoplastic agent. Medical success for Sm is, however, constrained by very low...

  6. Keratinocyte proliferation, differentiation, and apoptosis-Differential mechanisms of regulation by curcumin, EGCG and apigenin

    International Nuclear Information System (INIS)

    We have proposed that it is important to examine the impact of chemopreventive agents on the function of normal human epidermal keratinocytes since these cells comprise the barrier that protects the body from a range of environmental insults. In this context, it is widely appreciated that cancer may be retarded by consumption or topical application of naturally occurring food-derived chemopreventive agents. Our studies show that (-)-epigallocatechin-3-gallate (EGCG), a green tea-derived polyphenol, acts to enhance the differentiation of normal human keratinocytes as evidenced by its ability to increase involucrin (hINV), transglutaminase type 1 (TG1) and caspase-14 gene expression. EGCG also stimulates keratinocyte morphological differentiation. These actions of EGCG are mediated via activation of a nPKC, Ras, MEKK1, MEK3, p38δ-ERK1/2 signaling cascade which leads to increased activator protein 1 (AP1) and CAATT enhancer binding protein (C/EBP) transcription factor expression, increased binding of these factors to DNA, and increased gene transcription. In contrast, apigenin, a dietary flavonoid derived from plants and vegetables, and curcumin, an agent derived from turmeric, inhibit differentiation by suppressing MAPK signal transduction and reducing API transcription factor level. Curcumin also acts to enhance apoptosis, although EGCG and apigenin do not stimulate apoptosis. In addition, all of these agents inhibit keratinocyte proliferation. These findings indicate that each of these diet-derived chemopreventive agents has a profound impact on normal human keratinocyte function and that they operate via distinct and sometimes opposing mechanisms. However, all are expected to act as chemopreventive agents

  7. The Proapoptotic Effect of Traditional and Novel Nonsteroidal Anti-Inflammatory Drugs in Mammalian and Yeast Cells

    OpenAIRE

    Gianluca Farrugia; Rena Balzan

    2013-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) have long been used to treat pain, fever, and inflammation. However, mounting evidence shows that NSAIDs, such as aspirin, have very promising antineoplastic properties. The chemopreventive, antiproliferative behaviour of NSAIDs has been associated with both their inactivation of cyclooxygenases (COX) and their ability to induce apoptosis via pathways that are largely COX-independent. In this review, the various proapoptotic pathways induced by tr...

  8. Gene Expression Profiling Predicts the Development of Oral Cancer

    OpenAIRE

    Saintigny, Pierre; Zhang, Li; Fan, You-Hong; El-Naggar, Adel K.; Papadimitrakopoulou, Vali; Feng, Lei; Lee, J. Jack; Kim, Edward S.; Hong, Waun Ki; Mao, Li

    2011-01-01

    Patients with oral preneoplastic lesion (OPL) have high risk of developing oral cancer. Although certain risk factors such as smoking status and histology are known, our ability to predict oral cancer risk remains poor. The study objective was to determine the value of gene expression profiling in predicting oral cancer development. Gene expression profile was measured in 86 of 162 OPL patients who were enrolled in a clinical chemoprevention trial that used the incidence of oral cancer develo...

  9. In Vitro Action of Flavonoids in the Canine Malignant Histiocytic Cell Line DH82

    OpenAIRE

    Gabriel Silva; Ana Lúcia Fachin; Beleboni, Renê de O; Suzelei C. França; Mozart Marins

    2013-01-01

    Cancer is commonly diagnosed in dogs over the age of 10 and is a leading cause of death due to the lack of effective drugs. Flavonoids possess antioxidant, anti-inflammatory and anticarcinogenic properties and have been studied as chemopreventive agents in human cancer therapy. However, the literature on dogs is sparse. In this study, we analyzed the effect of nine flavonoids on cell viability, DNA damage and topoisomerase IIa/IIb gene expression in a canine tumor cell line (DH82). Apigenin, ...

  10. d-Limonene: a bioactive food component from citrus and evidence for a potential role in breast cancer prevention and treatment

    OpenAIRE

    Miller, Jessica A; Thompson, Patricia A; Hakim, Iman A; H.-H. Sherry Chow; Thomson, Cynthia A.

    2011-01-01

    Although limited, observations from cell culture, animal, and epidemiological studies support the presence of anti-cancer properties in citrus peel and the primary bioactive food constituent, d-limonene. Early evidence from animal models suggests that when ingested, d-limonene exhibits a wide spectrum of biologic activity including chemotherapeutic and chemopreventive effects. In some of these early models, an analog of d-limonene, perillyl alcohol, demonstrated a more potent effect than d-li...

  11. Effects of Resveratrol on Bone Mineral Density in Ovarectomized Rats

    OpenAIRE

    Lin, Qian; Huang, Yi-Ming; Xiao, Ben-xi; Ren, Guo-Feng

    2005-01-01

    Hormone replacement therapy (HRT) has been used to prevent osteoporosis in postmenopausal women. However, HRT is not for everyone, due to concerns of side effects as well as increased risk of breast and possibly uterine cancer. Therefore, Dietary alternatives are considered, which include Trans-3,5,4’-Trihydroxystilbene (trans-resveratrol), a phytoestrogen naturally found in grapes, peanuts and wine with beneficial effects in both cardioprotective and chemopreventive. The purpose of this stud...

  12. NSAIDs, Mitochondria and Calcium Signaling: Special Focus on Aspirin/Salicylates

    OpenAIRE

    Yoshihiro Suzuki; Toshio Inoue; Chisei Ra

    2010-01-01

    Aspirin (acetylsalicylic acid) is a well-known nonsteroidal anti-inflammatory drug (NSAID) that has long been used as an anti-pyretic and analgesic drug. Recently, much attention has been paid to the chemopreventive and apoptosis-inducing effects of NSAIDs in cancer cells. These effects have been thought to be primarily attributed to the inhibition of cyclooxygenase activity and prostaglandin synthesis. However, recent studies have demonstrated unequivocally that certain NSAIDs, including asp...

  13. Synergistic interactions among flavonoids and acetogenins in Graviola (Annona muricata) leaves confer protection against prostate cancer

    OpenAIRE

    Yang, Chunhua; Gundala, Sushma Reddy; Mukkavilli, Rao; Vangala, Subrahmanyam; Reid, Michelle D.; Aneja, Ritu

    2015-01-01

    Phytochemical complexity of plant extracts may offer health-promoting benefits including chemotherapeutic and chemopreventive effects. Isolation of ‘most-active fraction’ or single constituents from whole extracts may not only compromise the therapeutic efficacy but also render toxicity, thus emphasizing the importance of preserving the natural composition of whole extracts. The leaves of Annona muricata, commonly known as Graviola, are known to be rich in flavonoids, isoquinoline alkaloids a...

  14. EVALUATION OF ANTIBACTERIAL ACTIVITY AND PHYTOCHEMICAL ACTIVITY OF GARCINIA LANCIFOLIA ROXB.

    OpenAIRE

    T. Chowdhury* and P. J. Handique

    2012-01-01

    Flavonoids have been reported to have many pharmacological activities, antimicrobial, antioxidant, cytotoxic, chemoprevention activities along with strong antiproliferative effects. The fruits of Garcinia lancaefolia Roxb., family Cluseaceae , a plant endemic to Assam has been used in locally to treat many diseases for which it was selected for investigationg its antimicrobial properties. No scientific validation has been made so far on its phytochemical content and the antibacterial activit...

  15. Flavonoids, Flavonoid Subclasses, and Esophageal Cancer Risk: A Meta-Analysis of Epidemiologic Studies

    OpenAIRE

    Lingling Cui; Xinxin Liu; Yalan Tian; Chen Xie; Qianwen Li; Han Cui; Changqing Sun

    2016-01-01

    Flavonoids have been suggested to play a chemopreventive role in carcinogenesis. However, the epidemiologic studies assessing dietary intake of flavonoids and esophageal cancer risk have yielded inconsistent results. This study was designed to examine the association between flavonoids, each flavonoid subclass, and the risk of esophageal cancer with a meta-analysis approach. We searched for all relevant studies with a prospective cohort or case-control study design published from January 1990...

  16. Hereditary cancer risk assessment: essential tools for a better approach

    OpenAIRE

    Gomy, Israel; Estevez Diz, Maria Del Pilar

    2013-01-01

    Hereditary cancer risk assessment (HCRA) is a multidisciplinary process of estimating probabilities of germline mutations in cancer susceptibility genes and assessing empiric risks of cancer, based on personal and family history. It includes genetic counseling, testing and management of at-risk individuals so that they can make well-informed choices about cancer surveillance, surgical treatment and chemopreventive measures, including biomolecular cancer therapies. Providing patients and famil...

  17. Potential Effects of Pomegranate Polyphenols in Cancer Prevention and Therapy

    OpenAIRE

    Eleonora Turrini; Lorenzo Ferruzzi; Carmela Fimognari

    2015-01-01

    Cancer is the second leading cause of death and is becoming the leading one in old age. Vegetable and fruit consumption is inversely associated with cancer incidence and mortality. Currently, interest in a number of fruits high in polyphenols has been raised due to their reported chemopreventive and/or chemotherapeutic potential. Pomegranate has been shown to exert anticancer activity, which is generally attributed to its high content of polyphenols. This review provides a comprehensive analy...

  18. The evidence for solid lipid nanoparticles mediated cell uptake of resveratrol

    OpenAIRE

    Kristl, Julijana; Teskač, Karmen

    2015-01-01

    The potential for colloidal carriers to increase drug bioavailability has spurred a renewed interest in their uptake mechanisms and movement within cells. Solid lipid nanoparticles (SLN) were used as a carrier for a promising chemopreventive drug, resveratrol (RSV). The effects of SLN, empty or loaded with RSV (SLN-RSV), on the internalization, growth, morphology, metabolic activity and genetic material of keratinocytes were compared to those of RSV in solution. Fluorescence images clearly sh...

  19. In vitro evaluation of the antioxidant potential, phenolic and flavonoid contents of the stem bark ethanol extract of Anogeissus leiocarpus

    OpenAIRE

    Olugbami, JO; Gbadegesin, MA; Odunola, OA

    2014-01-01

    Plant-derived antioxidants with free radical scavenging activities can be relevant as chemopreventive agents against the numerous diseases associated with free radicals and reactive oxygen species. Some phytoconstituents possess antioxidant activities in biological systems. On this basis, we evaluated the antioxidant potential, and determined the total phenolic and flavonoid contents of the ethanol extract of the stem bark of Anogeissus leiocarpus [EESAL]. Antioxidant assays carried out inclu...

  20. Activation of Intestinal Human Pregnane X Receptor Protects against Azoxymethane/Dextran Sulfate Sodium–Induced Colon Cancer

    OpenAIRE

    Cheng, Jie; Fang, Zhong-Ze; Nagaoka, Kenjiro; Okamoto, Minoru; Qu, Aijuan; Tanaka, Naoki; Kimura, Shioko; Frank J. Gonzalez

    2014-01-01

    The role of intestinal human pregnane X receptor (PXR) in colon cancer was determined through investigation of the chemopreventive role of rifaximin, a specific agonist of intestinal human PXR, toward azoxymethane (AOM)/dextran sulfate sodium (DSS)–induced colon cancer. Rifaximin treatment significantly decreased the number of colon tumors induced by AOM/DSS treatment in PXR-humanized mice, but not wild-type or Pxr-null mice. Additionally, rifaximin treatment markedly increased the survival r...

  1. Tamoxifen Resistance in Breast Cancer

    OpenAIRE

    Chang, Minsun

    2012-01-01

    Tamoxifen is a central component of the treatment of estrogen receptor (ER)-positive breast cancer as a partial agonist of ER. It has been clinically used for the last 30 years and is currently available as a chemopreventive agent in women with high risk for breast cancer. The most challenging issue with tamoxifen use is the development of resistance in an initially responsive breast tumor. This review summarizes the roles of ER as the therapeutic target of tamoxifen in cancer treatment, clin...

  2. Tamoxifen for women at high risk of breast cancer

    OpenAIRE

    Nazarali SA; Narod SA

    2014-01-01

    Safia A Nazarali, Steven A Narod Women's College Research Institute, Women's College Hospital, and The University of Toronto, Toronto, Ontario, Canada Abstract: Tamoxifen has been used as a treatment for women who have been diagnosed with breast cancer for roughly four decades and has been approved as chemoprevention for over ten years. Although tamoxifen has been proven to be beneficial in preventing breast cancer in high-risk women, its use has not been widely embraced. To ...

  3. Aerosolized 3-bromopyruvate inhibits lung tumorigenesis without causing liver toxicity.

    Science.gov (United States)

    Zhang, Qi; Pan, Jing; North, Paula E; Yang, Shoua; Lubet, Ronald A; Wang, Yian; You, Ming

    2012-05-01

    3-Bromopyruvate, an alkylating agent and a well-known inhibitor of energy metabolism, has been proposed as a specific anticancer agent. However, the chemopreventive effect of 3-bromopyruvate in lung tumorigenesis has not been tested. In this study, we investigated the chemopreventive activity of 3-bromopyruvate in a mouse lung tumor model. Benzo(a)pyrene was used to induce lung tumors, and 3-bromopyruvate was administered by oral gavage to female A/J mice. We found that 3-bromopyruvate significantly decreased tumor multiplicity and tumor load by 58% and 83%, respectively, at a dose of 20 mg/kg body weight by gavage. Due to the known liver toxicity of 3-bromopyruvate in animal models given large doses of 3-bromopyruvate, confirmed in this study, we decided to test the chemopreventive activity of aerosolized 3-bromopyruvate in the same lung tumor model. As expected, aerosolized 3-bromopyruvate similarly significantly decreased tumor multiplicity and tumor load by 49% and 80%, respectively, at a dose of 10 mg/mL by inhalation. Interestingly, the efficacy of aerosolized 3-bromopyruvate did not accompany any liver toxicity indicating that it is a safer route of administering this compound. Treatment with 3-bromopyruvate increased immunohistochemical staining for cleaved caspase-3, suggesting that the lung tumor inhibitory effects of 3-bromopyruvate were through induction of apoptosis. 3-Bromopyruvate also dissociated hexokinase II from mitochondria, reduced hexokinase activity, and blocked energy metabolism in cancer cells, finally triggered cancer cell death and induced apoptosis through caspase-3, and PARP in human lung cancer cell line. The ability of 3-bromopyruvate to inhibit mouse lung tumorigenesis, in part through induction of apoptosis, merits further investigation of this compound as a chemopreventive agent for human lung cancer. PMID:22401980

  4. Evaluation of curcumin acetates and amino acid conjugates as proteasome inhibitors

    OpenAIRE

    WAN, SHENG BIAO; Yang, Huanjie; Zhou, Zhongyuan; Cui, Qiuzhi Cindy; Chen, Di; Kanwar, Jyoti; Mohammad, Imthiyaz; Dou, Q. Ping; CHAN, TAK HANG

    2010-01-01

    Curcumin (diferuloylmethane) is the main active ingredient of turmeric, a traditional herbal medicine and food of south Asia. Curcumin has been found to have a wide range of biological activities, including antioxidant, anti-inflammatory, chemopreventive and chemotherapeutic activities. Curcumin is currently being tested in clinical trials for treatment of various types of cancers, including multiple myeloma, pancreatic cancer and colon cancer. Although no toxicity associated with curcumin (e...

  5. CO-DELIVERY OF NATURAL METABOLIC INHIBITORS IN A SELF-MICROEMULSIFYING DRUG DELIVERY SYSTEM FOR IMPROVED ORAL BIOAVAILABILITY OF CURCUMIN

    OpenAIRE

    Grill, Alex E.; Koniar, Brenda; Panyam, Jayanth

    2014-01-01

    In spite of its well-documented anticancer chemopreventive and therapeutic activity, the clinical development of curcumin has been limited by its poor oral bioavailability. Curcumin has low aqueous solubility and undergoes extensive first pass metabolism following oral dosing. We hypothesized that oral bioavailability of curcumin can be enhanced by increasing its absorption and decreasing its metabolic clearance simultaneously. To test this hypothesis, we formulated curcumin with naturally oc...

  6. Thioredoxin reductase-1 (TxnRd1) mediates curcumin-induced radiosensitization of squamous carcinoma cells

    OpenAIRE

    Javvadi, Prashanthi; Hertan, Lauren; Kosoff, Rachelle; Datta, Tatini; Kolev, Johann; Mick, Rosemarie; Tuttle, Stephen W; Koumenis, Constantinos

    2010-01-01

    Curcumin, a plant polyphenol, is a widely studied chemopreventive agent with demonstrated antitumor activities in preclinical studies and low toxicity profiles in multiple clinical trials against human malignancies. We previously demonstrated that curcumin radiosensitizes cervical tumor cells without increasing the cytotoxic effects of radiation on normal human fibroblasts. Here we report that an inhibitory activity of curcumin on the anti-oxidant enzyme Thioredoxin Reductase-1 (TxnRd1) is re...

  7. The Effect of Curcumin on Breast Cancer Cells

    OpenAIRE

    Liu, Dongwu; Chen, Zhiwei

    2013-01-01

    Curcumin, which is extracted from the plant Curcuma longa, has been used in the therapeutic arsenal for clinical oncology. Curcumin has chemopreventive and antitumoral activities against some aggressive and recurrent cancers. The expressions and activities of various proteins, such as inflammatory cytokines and enzymes, transcription factors, and gene-products linked with cell survivals and proliferation, can be modified by curcumin. Moreover, curcumin decreases the toxic effect of mitomycin ...

  8. Inhibition of Lung Carcinogenesis by 1alpha,25-dihydroxyvitamin D3 and 9-cis Retinoic Acid in the A/J Mouse Model: Evidence of Retinoid Mitigation of Vitamin D Toxicity

    Science.gov (United States)

    9-cis-retinoic acid (9cRA) and 1alpha,25-dihydroxyvitamin D3 (1,25D) show promise as potential chemopreventive agents. We examined 9cRA and 1,25D, alone and in combination, for their potential to inhibit carcinogen (NNK)-induced lung carcinogenesis in A/J mice. A/J mice (n=14/group) were treated wit...

  9. Antiproliferative, apoptotic and antioxidant activities of wheatgrass (Triticum aestivum L.) extract on CML (K562) cell line

    OpenAIRE

    Aydos, Oya Sena; AVCI, Aslıhan; ÖZKAN, Tülin; KARADAĞ, Aynur; GÜRLEYİK, Ebru; ALTINOK, Buket; Sunguroğlu, Asuman

    2011-01-01

    Plant-based diet supplements help the prevention and therapy of several kinds of cancer because they contain micronutrients, a class of substances that have been shown to exhibit chemopreventive and chemotherapeutic activities. In the present study the effects and oxidant/antioxidant status of aqueous and ethanol extracts of wheatgrass were tested in human chronic myeloid leukemia CML (K562) cell line. Materials and methods: K562 cell lines were treated with 10% (w/v) concentration of aqueou...

  10. Omega 3 fatty acids chemosensitize multidrug resistant colon cancer cells by down-regulating cholesterol synthesis and altering detergent resistant membranes composition

    OpenAIRE

    Gelsomino, Giada; Corsetto, Paola A.; Campia, Ivana; Montorfano, Gigliola; Kopecka, Joanna; Castella, Barbara; Gazzano, Elena; Ghigo, Dario; Rizzo, Angela M; Riganti, Chiara

    2013-01-01

    Background The activity of P-glycoprotein (Pgp) and multidrug resistance related protein 1 (MRP1), two membrane transporters involved in multidrug resistance of colon cancer, is increased by high amounts of cholesterol in plasma membrane and detergent resistant membranes (DRMs). It has never been investigated whether omega 3 polyunsatured fatty acids (PUFAs), which modulate cholesterol homeostasis in dyslipidemic syndromes and have chemopreventive effects in colon cancer, may affect the respo...

  11. Metformin inhibits pancreatic cancer cell and tumor growth and downregulates Sp transcription factors

    OpenAIRE

    Nair, Vijayalekshmi; Pathi, Satya; Jutooru, Indira; Sreevalsan, Sandeep; Basha, Riyaz; Abdelrahim, Maen; Samudio, Ismael; Safe, Stephen

    2013-01-01

    Metformin is a widely used antidiabetic drug, and epidemiology studies for pancreatic and other cancers indicate that metformin exhibits both chemopreventive and chemotherapeutic activities. Several metformin-induced responses and genes are similar to those observed after knockdown of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 by RNA interference, and we hypothesized that the mechanism of action of metformin in pancreatic cancer cells was due, in part, to downregulation o...

  12. The low-toxicity 9-cis UAB30 novel retinoid down-regulates the DNA methyltransferases and has anti-telomerase activity in human breast cancer cells

    OpenAIRE

    HANSEN, NATHAN J.; WYLIE, REBECCA C.; Phipps, Sharla M. O.; Love, William K.; Andrews, Lucy G.; Tollefsbol, Trygve O.

    2007-01-01

    Retinoic acids and their derivatives potentiate anti-cancer effects in breast cancer cells. The aberrant expression of telomerase is critical to the continued proliferation of most cancer cells. Thus, telomerase is an attractive target for chemo-prevention and treatment of breast cancer. 9cUAB30 is a novel synthetic retinoid X receptor-selective retinoic acid (RA) that effectively reduces the tumorigenic phenotype in mouse breast carcinoma with lower toxic effects than natural retinoid treatm...

  13. The rexinoid, bexarotene, prevents the development of premalignant lesions in MMTV-erbB2 mice

    OpenAIRE

    Li, Y.; Zhang, Y.; Hill, J; Kim, H-T; Shen, Q.; Bissonnette, R P; Lamph, W W; Brown, P. H.

    2008-01-01

    Retinoids, vitamin A analogues that bind to retinoic acid receptor (RAR) or retinoid X receptor (RXR), play important roles in regulating cell proliferation, apoptosis, and differentiation. Recently, RXR-selective ligands, also referred to as rexinoids, have been investigated as potential chemopreventive agents for breast cancer. Our previous studies demonstrated that the rexinoid bexarotene significantly prevented ER-negative mammary tumourigenesis with less toxicity than naturally occurring...

  14. Retinoids: present role and future potential

    OpenAIRE

    Evans, T R J; Kaye, S B

    1999-01-01

    Vitamin A and its biologically active derivatives, retinal and retinoic acid (RA), together with a large repertoire of synthetic analogues are collectively referred to as retinoids. Naturally occurring retinoids regulate the growth and differentiation of a wide variety of cell types and play a crucial role in the physiology of vision and as morphogenic agents during embryonic development. Retinoids and their analogues have been evaluated as chemoprevention agents, and also in the management o...

  15. Differential expression of 5-alpha reductase isozymes in the prostate and its clinical implications

    OpenAIRE

    Kai Wang; Dong-Dong Fan; Song Jin; Nian-Zeng Xing; Yi-Nong Niu

    2014-01-01

    The development of human benign or malignant prostatic diseases is closely associated with androgens, primarily testosterone (T) and dihydrotestosterone (DHT). T is converted to DHT by 5-alpha reductase (5-AR) isozymes. Differential expression of 5-AR isozymes is observed in both human benign and malignant prostatic tissues. 5-AR inhibitors (5-ARI) are commonly used for the treatment of benign prostatic hyperplasia (BPH) and were once promoted as chemopreventive agents for prostate cancer (PC...

  16. Battling Prostate Cancer with 5-Alpha-Reductase Inhibitors: a Pyrrhic Victory?

    OpenAIRE

    Hoffman, Richard M.; Richard G. Roberts; Barry, Michael J.

    2011-01-01

    Given the relatively small impact of prostate cancer screening on cancer mortality, experts are now suggesting that chemoprevention with 5-alpha-reductase inhibitors (5-ARI) may be a more effective strategy for cancer control. Two large placebo-controlled randomized trials found that men receiving 5-ARI were about 25% less likely than controls to be detected with cancer. However, most cancers were detected on routine biopsies required by study protocols. The benefit from receiving 5-ARI was m...

  17. Five-alpha Reductase Inhibitor Influences Expression of Androgen Receptor and HOXB13 in Human Hyperplastic Prostate Tissue

    OpenAIRE

    Chaeyong Jung; Youngwoong Park; Young-Rang Kim; Soo Bang Ryu; Taek Won Kang

    2013-01-01

    Objectives Five-alpha reductase inhibitors (5ARIs) are known as chemopreventive agents in prostate cancer with a risk of high-grade disease. This study evaluated the effects of 5ARI on androgen receptor (AR) and proteins involved in prostate cell growth such as HOXB13 expression in human prostate tissue and LNCaP prostate cancer cells. Materials and Methods We retrospectively selected 21 patients who underwent TURP between March 2007 and February 2010 for previously confirmed BPH by prostate...

  18. 5-α reductase inhibitors and prostate cancer prevention: where do we turn now?

    OpenAIRE

    Hamilton Robert J; Freedland Stephen J

    2011-01-01

    Abstract With the lifetime risk of being diagnosed with prostate cancer so great, an effective chemopreventive agent could have a profound impact on the lives of men. Despite decades of searching for such an agent, physicians still do not have an approved drug to offer their patients. In this article, we outline current strategies for preventing prostate cancer in general, with a focus on the 5-α-reductase inhibitors (5-ARIs) finasteride and dutasteride. We discuss the two landmark randomized...

  19. Anti-cancer activities of pH- or heat-modified pectin

    OpenAIRE

    Leclere, Lionel; Van Cutsem, Pierre; Michiels, Carine

    2013-01-01

    Despite enormous efforts that have been made in the search for novel drugs and treatments, cancer continues to be a major public health problem. Moreover, the emergence of resistance to cancer chemotherapy often prevents complete remission. Researchers have thus turned to natural products mainly from plant origin to circumvent resistance. Pectin and pH- or heat-modified pectin have demonstrated chemopreventive and antitumoral activities against some aggressive and recurrent cancers. The focus...

  20. Nanomedicine and cancer therapies

    CERN Document Server

    Sebastian, Mathew; Elias, Eldho

    2012-01-01

    Introduction Nanotechnological-Based Systems for CancerIn vivo Spectroscopy for Detection and Treatment of GBM with NPt® ImplantationNanobiotechnology for Antibacterial Therapy and DiagnosisChitosan NanoparticlesSynthesis and Biomedical Application of Silver NanoparticlesRecent Advances in Cancer Therapy Using PhytochemicalsMitochondrial Dysfunction and Cancer: Modulation by Palladium-Lipoic Acid ComplexUnity of Mind and Body: The Concept of Life Purpose DominantThuja Occidentalis and Breast Cancer ChemopreventionAntioxidants and Com