Molecular medicine and the development of cancer chemopreventive agents.

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Izzotti, Alberto

2012-07-01

Chemoprevention is effective in inhibiting the onset of cancer in experimental animal models, but the transferability of similar results to humans is questionable. Therefore, reliable intermediate molecular biomarkers are needed to evaluate the efficacy of chemopreventive agents before the onset of cancer. The use of genomic biomarkers is limited by their poor predictive value. Although post-genomic biomarkers (i.e., gene-expression analyses) are useful for evaluating the safety, efficacy, and mechanistic basis of chemopreventive agents, the biomarkers are often poorly related to the phenotype, due to posttranscriptional regulation. Proteome analyses can evaluate preclinical phenotype alterations, but only at low protein counts. MicroRNA alterations, which are essential for the development of cancer, may be modulated by chemopreventive agents. Furthermore, microRNA delivery may be used to counteract carcinogenesis. Exposure to cigarette smoke induces microRNA let-7 downregulation and cell proliferation that can be converted to cell growth arrest and apoptosis upon let-7a transfection. Therefore, microRNAs are reliable biomarkers for evaluating chemoprevention efficacy and may be used to counteract carcinogenesis. © 2012 New York Academy of Sciences.

A Chemopreventive Nanodiamond Platform for Oral Cancer Treatment.

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Yen, Albert; Zhang, Kangyi; Daneshgaran, Giulia; Kim, Ho-Joong; Ho, Dean

2016-02-01

Standard oral cancer therapy generally includes a combination of surgery with chemotherapy and/or radiotherapy. This treatment paradigm has not changed in some time. In this paper, we propose a chemopreventive nanodiamond platform for the delivery of celecoxib (Celebrex) to oral cancer lesions. This innovative platform allows for sustained drug release under physiological conditions, potentially enhancing chemopreventive efficacy of celecoxib without the physical and toxicological damage associated with conventional means of drug delivery.

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

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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.

Moringa oleifera Lam: Targeting Chemoprevention.

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

2016-01-01

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

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

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

2006-12-15

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

[Coffee in Cancer Chemoprevention].

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

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

Colon Cancer Chemoprevention by Flavonoid Silibinin | Division of Cancer Prevention

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

Cancer chemopreventive and therapeutic effects of diosgenin, a food saponin.

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Raju, Jayadev; Mehta, Rekha

2009-01-01

Cancer chemoprevention is a strategy taken to retard, regress, or resist the multistep process of carcinogenesis, including the blockage of its vital morphogenetic milestones viz. normal-preneoplasia-neoplasia-metastasis. For several reasons, including safety, minimal (or no) toxicity and side-effects, and better availability, alternatives such as naturally occurring phytochemicals that are found in foods are becoming increasingly popular over synthetic drugs. Food saponins have been used in complimentary and traditional medicine against a variety of diseases including several cancers. Diosgenin, a naturally occurring steroid saponin found abundantly in legumes and yams, is a well-known precursor of various synthetic steroidal drugs that are extensively used in the pharmaceutical industry. Over the past decade, a series of preclinical and mechanistic studies have been conducted to understand the role of diosgenin as a chemopreventive/therapeutic agent against several cancers. This review highlights the biological activity of diosgenin that contributes to cancer chemoprevention and control. The anticancer mode of action of diosgenin has been demonstrated via modulation of multiple cell signaling events involving critical molecular candidates associated with growth, differentiation, apoptosis, and oncogenesis. Altogether, these preclinical and mechanistic findings strongly implicate the use of diosgenin as a novel, multitarget-based chemopreventive or therapeutic agent against several cancer types. Future research in this field will help to establish not only whether diosgenin is safe and efficacious as a chemopreventive agent against several human cancers, but also to develop and evaluate standards of evidence for health claims for diosgenin-containing foods as they become increasingly popular and enter the marketplace labeled as functional foods and nutraceuticals.

Using Breast Cancer Risk Associated Polymorphisms to Identify Women for Breast Cancer Chemoprevention.

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Elad Ziv

Full Text Available Breast cancer can be prevented with selective estrogen receptor modifiers (SERMs and aromatase inhibitors (AIs. The US Preventive Services Task Force recommends that women with a 5-year breast cancer risk ≥3% consider chemoprevention for breast cancer. More than 70 single nucleotide polymorphisms (SNPs have been associated with breast cancer. We sought to determine how to best integrate risk information from SNPs with other risk factors to risk stratify women for chemoprevention.We used the risk distribution among women ages 35-69 estimated by the Breast Cancer Surveillance Consortium (BCSC risk model. We modeled the effect of adding 70 SNPs to the BCSC model and examined how this would affect how many women are reclassified above and below the threshold for chemoprevention.We found that most of the benefit of SNP testing a population is achieved by testing a modest fraction of the population. For example, if women with a 5-year BCSC risk of >2.0% are tested (~21% of all women, ~75% of the benefit of testing all women (shifting women above or below 3% 5-year risk would be derived. If women with a 5-year risk of >1.5% are tested (~36% of all women, ~90% of the benefit of testing all women would be derived.SNP testing is effective for reclassification of women for chemoprevention, but is unlikely to reclassify women with <1.5% 5-year risk. These results can be used to implement an efficient two-step testing approach to identify high risk women who may benefit from chemoprevention.

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

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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.

Aspirin Metabolomics in Colorectal Cancer Chemoprevention | Division of Cancer Prevention

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Substantial evidence supports the effectiveness of aspirin for cancer chemoprevention in addition to its well-established role in cardiovascular protection. In recent meta-analyses of randomized controlled trials in humans, daily aspirin use reduced incidence, metastasis and mortality from several common types of cancer, especially colorectal cancer. The mechanism(s) by which

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

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Sabita N. Saldanha

2012-01-01

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

Use of nonsteroidal antiinflamatory drugs for chemoprevention of colon cancer

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Milić Aleksandra

2013-01-01

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

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

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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.

Sulforaphane (SFN: An Isothiocyanate in a Cancer Chemoprevention Paradigm

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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.

Acceptance and adherence to chemoprevention among women at increased risk of breast cancer.

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Roetzheim, Richard G; Lee, Ji-Hyun; Fulp, William; Matos Gomez, Elizabeth; Clayton, Elissa; Tollin, Sharon; Khakpour, Nazanin; Laronga, Christine; Lee, Marie Catherine; Kiluk, John V

2015-02-01

Chemoprevention is an option for women who are at increased risk of breast cancer (five year risk ≥1.7%). It is uncertain, however, how often women accept and complete five years of therapy and whether clinical or demographic factors predict completion. Medical records were abstracted for 219 women whose five year risk of breast cancer was ≥1.7% and who were offered chemoprevention while attending a high risk breast clinic at the Moffitt Cancer Center. We examined the likelihood of accepting chemoprevention and completing five years of therapy, and potential clinical and demographic predictors of these outcomes, using multivariable logistic regression and survival analysis models. There were 118/219 women (54.4%) who accepted a recommendation for chemoprevention and began therapy. The likelihood of accepting chemoprevention was associated with lifetime breast cancer risk and was higher for women with specific high risk conditions (lobular carcinoma in situ and atypical ductal hyperplasia). Women with osteoporosis and those that consumed alcohol were also more likely to accept medication. There were 58/118 (49.2%) women who stopped medication at least temporarily after starting therapy. Based on survival curves, an estimated 60% of women who begin chemoprevention will complete five years of therapy. A substantial percentage of women at increased risk of breast cancer will decline chemoprevention and among those that accept therapy, approximately 40% will not be able to complete five years of therapy because of side effects. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

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

2017-05-03

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

Nanoencapsulation of pomegranate bioactive compounds for breast cancer chemoprevention.

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

2015-01-01

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

Arsenic and skin cancer – Case report with chemoprevention

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Uwe Wollina

2016-04-01

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

Epigenetic Regulation by Sulforaphane: Opportunities for Breast and Prostate Cancer Chemoprevention.

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Atwell, Lauren L; Beaver, Laura M; Shannon, Jackilen; Williams, David E; Dashwood, Roderick H; Ho, Emily

2015-04-01

Sulforaphane (SFN) is a phytochemical derived from cruciferous vegetables that has multiple molecular targets and anti-cancer properties. Researchers have demonstrated several chemopreventive benefits of SFN consumption, such as reductions in tumor growth, increases in cancer cell apoptosis, and disruption of signaling within tumor microenvironments both in vitro and in vivo . Emerging evidence indicates that SFN exerts several of its chemopreventive effects by altering epigenetic mechanisms. This review summarizes evidence of the impact of SFN on epigenetic events and how they relate to the chemopreventive effects of SFN observed in preclinical and clinical studies of breast and prostate cancers. Specific areas of focus include the role of SFN in the regulation of cell cycle, apoptosis, inflammation, antioxidant defense, and cancer cell signaling and their relationships to epigenetic mechanisms. Finally, remaining challenges and research needs for translating mechanistic work with SFN into human studies and clinical intervention trials are discussed.

Phyto-oestrogens and breast cancer chemoprevention

International Nuclear Information System (INIS)

Limer, Jane L; Speirs, Valerie

2004-01-01

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

Chemoprevention of hormone-dependent prostate cancer in the Wistar-Unilever rat.

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McCormick, D L; Rao, K V

1999-01-01

The high incidence and long latent period of prostate cancer make it an ideal target for chemoprevention. We have evaluated a series of agents for chemopreventive efficacy using a model in which hormone-dependent prostate cancers are induced in the Wistar-Unilever (WU) rat by sequential treatment with antiandrogen (cyproterone acetate), androgen (testosterone propionate), and direct-acting chemical carcinogen (N-methyl-N-nitrosourea), followed by chronic androgen stimulation (testosterone). This regimen reproducibly induces prostate cancers in high incidence, with no gross toxicity and a low incidence of neoplasia in the seminal vesicle and other non-target tissues. Dehydroepiandrosterone (DHEA) and 9-cis-retinoic acid (9-cis-RA) are the most active agents identified to date. DHEA inhibits prostate cancer induction both when chronic administration is begun prior to carcinogen exposure, and when administration is delayed until preneoplastic prostate lesions are present. 9-cis-RA is the most potent inhibitor of prostate carcinogenesis identified; a study to determine the efficacy of delayed administration of 9-cis-RA is in progress. Liarozole fumarate confers modest protection against prostate carcinogenesis, while N-(4-hydroxyphenyl)retinamide (fenretinide), alpha-difluoromethylornithine, oltipraz, DL-alpha-tocopherol acetate (vitamin E), and L-selenomethionine are inactive. Chemoprevention efficacy evaluations in the WU rat will support the identification of agents that merit study for prostate cancer chemoprevention in humans.

Oleuropein and Cancer Chemoprevention: The Link is Hot

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Ammad Ahmad Farooqi

2017-04-01

Full Text Available Cancer comprises a collection of related diseases characterized by the existence of altered cellular pathways resulting in an abnormal tendency for uncontrolled growth. A broad spectrum, coordinated, and personalized approach focused on targeting diverse oncogenic pathways with low toxicity and economic natural compounds can provide a real benefit as a chemopreventive and/or treatment of this complex disease. Oleuropein, a bioactive phenolic compound mainly present in olive oil and other natural sources, has been reported to modulate several oncogenic signalling pathways. This review presents and critically discusses the available literature about the anticancer and onco-suppressive activity of oleuropein and the underlying molecular mechanisms implicated in the anticarcinogenic and therapeutic effects. The existence of limitations and the promising perspectives of research on this phenolic compound are also critically analyzed and discussed.

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...

Cancer Chemopreventive Ability of Conjugated Linolenic Acids

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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.

Cancer chemoprevention through dietary flavonoids: what's limiting?

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Amawi, Haneen; Ashby, Charles R; Tiwari, Amit K

2017-06-19

Flavonoids are polyphenols that are found in numerous edible plant species. Data obtained from preclinical and clinical studies suggest that specific flavonoids are chemo-preventive and cytotoxic against various cancers via a multitude of mechanisms. However, the clinical use of flavonoids is limited due to challenges associated with their effective use, including (1) the isolation and purification of flavonoids from their natural resources; (2) demonstration of the effects of flavonoids in reducing the risk of certain cancer, in tandem with the cost and time needed for epidemiological studies, and (3) numerous pharmacokinetic challenges (e.g., bioavailability, drug-drug interactions, and metabolic instability). Currently, numerous approaches are being used to surmount some of these challenges, thereby increasing the likelihood of flavonoids being used as chemo-preventive drugs in the clinic. In this review, we summarize the most important challenges and efforts that are being made to surmount these challenges.

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....

Colorectal cancer chemoprevention: the potential of a selective approach.

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Ben-Amotz, Oded; Arber, Nadir; Kraus, Sarah

2010-10-01

Colorectal cancer (CRC) is a leading cause of cancer death, and therefore demands special attention. Novel recent approaches for the chemoprevention of CRC focus on selective targeting of key pathways. We review the study by Zhang and colleagues, evaluating a selective approach targeting APC-deficient premalignant cells using retinoid-based therapy and TNF-related apoptosis-inducing ligand (TRAIL). This study demonstrates that induction of TRAIL-mediated death signaling contributes to the chemopreventive value of all-trans-retinyl acetate (RAc) by sensitizing premalignant adenoma cells for apoptosis without affecting normal cells. We discuss these important findings, raise few points that deserve consideration, and may further contribute to the development of RAc-based combination therapies with improved efficacy. The authors clearly demonstrate a synergistic interaction between TRAIL, RAc and APC, which leads to the specific cell death of premalignant target cells. The study adds to the growing body of literature related to CRC chemoprevention, and provides solid data supporting a potentially selective approach for preventing CRC using RAc and TRAIL.

Lung Cancer Chemopreventive Activity of Patulin Isolated from Penicillium vulpinum

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Aymeric Monteillier

2018-03-01

Full Text Available Lung cancer is the most lethal form of cancer in the world. Its development often involves an overactivation of the nuclear factor kappa B (NF-κB pathway, leading to increased cell proliferation, survival, mobility, and a decrease in apoptosis. Therefore, NF-κB inhibitors are actively sought after for both cancer chemoprevention and therapy, and fungi represent an interesting unexplored reservoir for such molecules. The aim of the present work was to find naturally occurring lung cancer chemopreventive compounds by investigating the metabolites of Penicillium vulpinum, a fungus that grows naturally on dung. Penicillium vulpinum was cultivated in Potato Dextrose Broth and extracted with ethyl acetate. Bioassay-guided fractionation of this extract was performed by measuring NF-κB activity using a HEK293 cell line transfected with an NF-κB-driven luciferase reporter gene. The mycotoxin patulin was identified as a nanomolar inhibitor of TNF-α-induced NF-κB activity. Immunocytochemistry and Western blot analyses revealed that its mechanism of action involved an inhibition of p65 nuclear translocation and was independent from the NF-κB inhibitor α (IκBα degradation process. Enhancing its interest in lung cancer chemoprevention, patulin also exhibited antiproliferative, proapoptotic, and antimigration effects on human lung adenocarcinoma cells through inhibition of the Wnt pathway.

Comet Assay in Cancer Chemoprevention.

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

2016-01-01

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

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

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Rafieian-Kopaei, Mahmoud; Movahedi, Mino

2017-02-01

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

Advanced Drug-Delivery Systems of Curcumin for Cancer Chemoprevention

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

2011-01-01

From 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, anti-oxidant, anti-proliferative, anti-carcinogenic, and anti-angiogenic activity in various cell culture and some animal studies. Research over the past four 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 demonstrated 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

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

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

2017-11-01

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

The chemopreventive properties and therapeutic modulation of green tea polyphenols in oral squamous cell carcinoma.

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Lee, Ui-Lyong; Choi, Sung-Weon

2011-01-01

Chemoprevention is a relatively novel and promising approach for controlling cancer that uses specific natural products or synthetic agents to suppress, reverse, or prevent premalignancy before transformation into invasive cancer. Oral cavity squamous cell carcinoma (OCSCC) represents a large, worldwide health burden with approximately 274,000 cases diagnosed annually worldwide. Smoking and alcohol consumption are major inducers of OCSCC. Recently, the human papilloma virus was also shown to potentially be an etiologic factor. Due to its easily identifiable risk factors and the presence of premalignant regions, oral cancer makes a good candidate for chemoprevention. Green tea is the most widely consumed beverage in the world, and it has received considerable attention because of its abundant, scientifically proven, beneficial effects on human health. In this review, we discuss the role of green tea in oral cancer chemoprevention with regard to the multiple molecular mechanisms proposed in various in vitro, in vivo, and clinical trials.

Overview of mechanisms of cancer chemopreventive agents

International Nuclear Information System (INIS)

De Flora, Silvio; Ferguson, Lynnette R.

2005-01-01

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

Curcumin and Other Polyphenolic Compounds in Head and Neck Cancer Chemoprevention

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Philipp Baumeister

2012-01-01

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

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

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Zhenyu Wang

2017-05-01

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

Colon cancer chemoprevention by a novel NO chimera that shows anti-inflammatory and antiproliferative activity in vitro and in vivo.

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Hagos, Ghenet K; Carroll, Robert E; Kouznetsova, Tatiana; Li, Qian; Toader, Violeta; Fernandez, Patricia A; Swanson, Steven M; Thatcher, Gregory R J

2007-08-01

Chemopreventive agents in colorectal cancer possess either antiproliferative or anti-inflammatory actions. Nonsteroidal anti-inflammatory drugs (NSAID) and cyclooxygenase-2 inhibitors have shown promise, but are compromised by side effects. Nitric oxide donor NSAIDs are organic nitrates conjugated via a labile linker to an NSAID, originally designed for use in pain relief, that have shown efficacy in colorectal cancer chemoprevention. The NO chimera, GT-094, is a novel nitrate containing an NSAID and disulfide pharmacophores, a lead compound for the design of agents specifically for colorectal cancer. GT-094 is the first nitrate reported to reduce aberrant crypt foci (by 45%) when administered after carcinogen in the standard azoxymethane rat model of colorectal cancer. Analysis of proximal and distal colon tissue from 8- and 28-week rat/azoxymethane studies showed that GT-094 treatment reduced colon crypt proliferation by 30% to 69%, reduced inducible NO synthase (iNOS) levels by 33% to 67%, reduced poly(ADP-ribose)polymerase-1 expression and cleavage 2- to 4-fold, and elevated levels of p27 in the distal colon 3-fold. Studies in cancer cell cultures recapitulated actions of GT-094: antiproliferative activity and transient G(2)-M phase cell cycle block were measured in Caco-2 cells; apoptotic activity was examined but not observed; anti-inflammatory activity was seen in the inhibition of up-regulation of iNOS and endogenous NO production in lipopolysaccharide (LPS)-induced RAW 264.7 cells. In summary, antiproliferative, anti-inflammatory, and cytoprotective activity observed in vivo and in vitro support GT-094 as a lead compound for the design of NO chimeras for colorectal cancer chemoprevention.

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

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

2015-01-01

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

Chemoprevention of cancer: an ongoing saga.

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Kellen, J A

1999-01-01

The trivial adage "an ounce of prevention..." is certainly appropriate in oncology; cancer has and continues to have an enormous impact on morbidity, suffering, socioeconomics and mortality. Curative therapy is elusive--cancer remains a mainly lethal disease, which makes the objective of prevention even more important and attractive. Sober estimates put the potentially avoidable or preventable cancers in the Western World at 80% (1): the effects of smoking and alcohol, being overweight, diet promiscuity and other lifestyle choices are well known, yet at the individual level, corrective measures are disappointingly ignored. Lately, this issue is being further weakened by our acceptance of inherited susceptibility--why change our habits and indulgences, if we can not escape our genetic destiny? However, there is a massive and growing amount of information on chemoprevention which needs to be carefully evaluated, in the hope that someday, we should be able to avoid or at least delay cancer by the use of natural or synthetic compounds which intervene in the early precancerous process.

Targeting Chemoprevention of Colorectal Cancer to Those Who Are Likely to Respond

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Stockbrugger, Reinhold W.

2010-01-01

In the past four decades, chemoprevention of colorectal cancer (CRC) has been the subject of many epidemiologic and intervention trials of naturally occurring or pharmacologic agents. Recently, the positioning of cyclooxygenase 2 inhibitors as a viable option in this context was a major breakthrough; however, it was hampered by adverse cardiovascular events. This review questions whether chemopreventive measures for CRC are ready to be used in mass or individual applications, standing alone o...

A Review of the Potential of Phytochemicals from Prunus africana (Hook f. Kalkman Stem Bark for Chemoprevention and Chemotherapy of Prostate Cancer

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Richard Komakech

2017-01-01

Full Text Available Prostate cancer remains one of the major causes of death worldwide. In view of the limited treatment options for patients with prostate cancer, preventive and treatment approaches based on natural compounds can play an integral role in tackling this disease. Recent evidence supports the beneficial effects of plant-derived phytochemicals as chemopreventive and chemotherapeutic agents for various cancers, including prostate cancer. Prunus africana has been used for generations in African traditional medicine to treat prostate cancer. This review examined the potential roles of the phytochemicals from P. africana, an endangered, sub-Saharan Africa plant in the chemoprevention and chemotherapy of prostate cancer. In vitro and in vivo studies have provided strong pharmacological evidence for antiprostate cancer activities of P. africana-derived phytochemicals. Through synergistic interactions between different effective phytochemicals, P. africana extracts have been shown to exhibit very strong antiandrogenic and antiangiogenic activities and have the ability to kill tumor cells via apoptotic pathways, prevent the proliferation of prostate cancer cells, and alter the signaling pathways required for the maintenance of prostate cancer cells. However, further preclinical and clinical studies ought to be done to advance and eventually use these promising phytochemicals for the prevention and chemotherapy of human prostate cancer.

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

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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.

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

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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.

Null activity of selenium and vitamin e as cancer chemopreventive agents in the rat prostate.

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McCormick, David L; Rao, K V N; Johnson, William D; Bosland, Maarten C; Lubet, Ronald A; Steele, Vernon E

2010-03-01

To evaluate the potential efficacy of selenium and vitamin E as inhibitors of prostate carcinogenesis, four chemoprevention studies using a common protocol were done in a rat model of androgen-dependent prostate cancer. After stimulation of prostate epithelial cell proliferation by a sequential regimen of cyproterone acetate followed by testosterone propionate, male Wistar-Unilever rats received a single i.v. injection of N-methyl-N-nitrosourea (MNU) followed by chronic androgen stimulation via subcutaneous implantation of testosterone pellets. At 1 week post-MNU, groups of carcinogen-treated rats (39-44/group) were fed either a basal diet or a basal diet supplemented with l-selenomethionine (3 or 1.5 mg/kg diet; study 1), dl-alpha-tocopherol (vitamin E, 4,000 or 2,000 mg/kg diet; study 2), l-selenomethionine + vitamin E (3 + 2,000 mg/kg diet or 3 + 500 mg/kg diet; study 3), or selenized yeast (target selenium levels of 9 or 3 mg/kg diet; study 4). Each chemoprevention study was terminated at 13 months post-MNU, and prostate cancer incidence was determined by histopathologic evaluation. No statistically significant reductions in prostate cancer incidence were identified in any group receiving dietary supplementation with selenium and/or vitamin E. These data do not support the hypotheses that selenium and vitamin E are potent cancer chemopreventive agents in the prostate, and when considered with the recent clinical data reported in the Selenium and Vitamin E Cancer Prevention Trial (SELECT), show the predictive nature of this animal model for human prostate cancer chemoprevention.

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

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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.

Colon Cancer Chemoprevention by Sage Tea Drinking: Decreased DNA Damage and Cell Proliferation.

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Pedro, Dalila F N; Ramos, Alice A; Lima, Cristovao F; Baltazar, Fatima; Pereira-Wilson, Cristina

2016-02-01

Salvia officinalis and some of its isolated compounds have been found to be preventive of DNA damage and increased proliferation in vitro in colon cells. In the present study, we used the azoxymethane model to test effects of S. officinalis on colon cancer prevention in vivo. The results showed that sage treatment reduced the number of ACF formed only if administered before azoxymethane injection, demonstrating that sage tea drinking has a chemopreventive effect on colorectal cancer. A decrease in the proliferation marker Ki67 and in H2 O2 -induced and azoxymethane-induced DNA damage to colonocytes and lymphocytes were found with sage treatment. This confirms in vivo the chemopreventive effects of S. officinalis. Taken together, our results show that sage treatment prevented initiation phases of colon carcinogenesis, an effect due, at least in part, to DNA protection, and reduced proliferation rates of colon epithelial cell that prevent mutations and their fixation through cell replication. These chemopreventive effects of S. officinalis on colon cancer add to the many health benefits attributed to sage and encourage its consumption. Copyright © 2015 John Wiley & Sons, Ltd.

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

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Elena Maria Varoni

2013-07-01

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

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

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Bagde, Arvind; Mondal, Arindam; Singh, Mandip

2018-01-01

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

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

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

2011-06-22

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

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

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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.

Targeting Chemoprevention of Colorectal Cancer to Those Who Are Likely to Respond.

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Stockbrugger, Reinhold W

2010-01-01

In the past four decades, chemoprevention of colorectal cancer (CRC) has been the subject of many epidemiologic and intervention trials of naturally occurring or pharmacologic agents. Recently, the positioning of cyclooxygenase 2 inhibitors as a viable option in this context was a major breakthrough; however, it was hampered by adverse cardiovascular events. This review questions whether chemopreventive measures for CRC are ready to be used in mass or individual applications, standing alone or in combination with other CRC-preventive measures. It also discusses steps that may be undertaken to explore this field further.

Regulatory approval of cancer risk-reducing (chemopreventive) drugs: moving what we have learned into the clinic.

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Meyskens, Frank L; Curt, Gregory A; Brenner, Dean E; Gordon, Gary; Herberman, Ronald B; Finn, Olivera; Kelloff, Gary J; Khleif, Samir N; Sigman, Caroline C; Szabo, Eva

2011-03-01

This article endeavors to clarify the current requirements and status of regulatory approval for chemoprevention (risk reduction) drugs and discusses possible improvements to the regulatory pathway for chemoprevention. Covering a wide range of topics in as much depth as space allows, this report is written in a style to facilitate the understanding of nonscientists and to serve as a framework for informing the directions of experts engaged more deeply with this issue. Key topics we cover here are as follows: a history of definitive cancer chemoprevention trials and their influence on the evolution of regulatory assessments; a brief review of the long-standing success of pharmacologic risk reduction of cardiovascular diseases and its relevance to approval for cancer risk reduction drugs; the use and limitations of biomarkers for developing and the approval of cancer risk reduction drugs; the identification of individuals at a high(er) risk for cancer and who are appropriate candidates for risk reduction drugs; business models that should incentivize pharmaceutical industry investment in cancer risk reduction; a summary of scientific and institutional barriers to development of cancer risk reduction drugs; and a summary of major recommendations that should help facilitate the pathway to regulatory approval for pharmacologic cancer risk reduction drugs.

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

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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.

Endotoxin and cancer chemo-prevention.

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Mastrangelo, Giuseppe; Fadda, Emanuela; Cegolon, Luca

2013-10-01

Reduced rates of lung cancer have been observed in several occupational groups exposed to high levels of organic dusts contaminated by endotoxin. The underlying anti-neoplastic mechanism of endotoxin may be an increased secretion of endogenous anti-neoplastic mediators and activation of the toll-like receptors (TLR). A detoxified endotoxin derivative, Monophosphoryl Lipid A (MPL(®)) is marketed in Europe since 1999 as part of the adjuvant systems in allergy vaccines for treatment of allergic rhino-conjunctivitis and allergic asthma. Over 200,000 patients have used them to date (nearly 70% in Germany). Since detailed exposure (MPL(®) dose and timing of administration) and individual data are potentially available, an observational follow-up study could be conducted in Germany to investigate the protective effect of MPL(®) against cancer, comparing cancer incidence in two groups of patients with allergic rhinitis: those treated with allergoids plus MPL(®) and those treated with a vaccine including the same allergoids but not MPL(®). The protective effect of MPL(®) could be quantified in ever and never smokers. If this proposed observational study provides evidence of protective effects, MPL(®) could be immediately used as a chemo-preventive agent since it is already in use as adjuvant in human vaccines against cancer. Copyright © 2013 Elsevier Ltd. All rights reserved.

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.

Combination chemoprevention with grape antioxidants.

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Singh, Chandra K; Siddiqui, Imtiaz A; El-Abd, Sabah; Mukhtar, Hasan; Ahmad, Nihal

2016-06-01

Antioxidant ingredients present in grape have been extensively investigated for their cancer chemopreventive effects. However, much of the work has been done on individual ingredients, especially focusing on resveratrol and quercetin. Phytochemically, whole grape represents a combination of numerous phytonutrients. Limited research has been done on the possible synergistic/additive/antagonistic interactions among the grape constituents. Among these phytochemical constituents of grapes, resveratrol, quercetin, kaempferol, catechin, epicatechin, and anthocyanins (cyanidin and malvidin) constitute more than 70% of the grape polyphenols. Therefore, these have been relatively well studied for their chemopreventive effects against a variety of cancers. While a wealth of information is available individually on cancer chemopreventive/anti-proliferative effects of resveratrol and quercetin, limited information is available regarding the other major constituents of grape. Studies have also suggested that multiple grape antioxidants, when used in combination, alone or with other agents/drugs show synergistic or additive anti-proliferative response. Based on strong rationale emanating from published studies, it seems probable that a combination of multiple grape ingredients alone or together with other agents could impart 'additive synergism' against cancer. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Carnosol: a promising anti-cancer and anti-inflammatory agent.

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Johnson, Jeremy J

2011-06-01

The Mediterranean diet and more specifically certain meats, fruits, vegetables, and olive oil found in certain parts of the Mediterranean region have been associated with a decreased cardiovascular and diabetes risk. More recently, several population based studies have observed with these lifestyle choices have reported an overall reduced risk for several cancers. One study in particular observed an inverse relationship between consumption of Mediterranean herbs such as rosemary, sage, parsley, and oregano with lung cancer. In light of these findings there is a need to explore and identify the anti-cancer properties of these medicinal herbs and to identify the phytochemicals therein. One agent in particular, carnosol, has been evaluated for anti-cancer property in prostate, breast, skin, leukemia, and colon cancer with promising results. These studies have provided evidence that carnosol targets multiple deregulated pathways associated with inflammation and cancer that include nuclear factor kappa B (NFκB), apoptotic related proteins, phosphatidylinositol-3-kinase (PI3 K)/Akt, androgen and estrogen receptors, as well as molecular targets. In addition, carnosol appears to be well tolerated in that it has a selective toxicity towards cancer cells versus non-tumorigenic cells and is well tolerated when administered to animals. This mini-review reports on the pre-clinical studies that have been performed to date with carnosol describing mechanistic, efficacy, and safety/tolerability studies as a cancer chemoprevention and anti-cancer agent. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

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

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Isnatin Miladiyah

2016-01-01

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

Evidence supporting the conceptual framework of cancer chemoprevention in canines.

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

2016-05-24

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".

Molecular Mechanisms Behind the Chemopreventive Effects of Anthocyanidins

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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.

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.

Update on the chemopreventive effects of ginger and its phytochemicals.

Science.gov (United States)

Baliga, Manjeshwar Shrinath; Haniadka, Raghavendra; Pereira, Manisha Maria; D'Souza, Jason Jerome; Pallaty, Princy Louis; Bhat, Harshith P; Popuri, Sandhya

2011-07-01

The rhizomes of Zingiber officinale Roscoe (Zingiberaceae), commonly known as ginger, is one of the most widely used spice and condiment. It is also an integral part of many traditional medicines and has been extensively used in Chinese, Ayurvedic, Tibb-Unani, Srilankan, Arabic, and African traditional medicines, since antiquity, for many unrelated human ailments including common colds, fever, sore throats, vomiting, motion sickness, gastrointestinal complications, indigestion, constipation, arthritis, rheumatism, sprains, muscular aches, pains, cramps, hypertension, dementia, fever, infectious diseases, and helminthiasis. The putative active compounds are nonvolatile pungent principles, namely gingerols, shogaols, paradols, and zingerone. These compounds are some of the extensively studied phytochemicals and account for the antioxidant, anti-inflammatory, antiemetic, and gastroprotective activities. A number of preclinical investigations with a wide variety of assay systems and carcinogens have shown that ginger and its compounds possess chemopreventive and antineoplastic effects. A number of mechanisms have been observed to be involved in the chemopreventive effects of ginger. The cancer preventive activities of ginger are supposed to be mainly due to free radical scavenging, antioxidant pathways, alteration of gene expressions, and induction of apoptosis, all of which contribute towards decrease in tumor initiation, promotion, and progression. This review provides concise information from preclinical studies with both cell culture models and relevant animal studies by focusing on the mechanisms responsible for the chemopreventive action. The conclusion describes directions for future research to establish its activity and utility as a human cancer preventive and therapeutic drug. The above-mentioned mechanisms of ginger seem to be promising for cancer prevention; however, further clinical studies are warranted to assess the efficacy and safety of ginger.

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

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Mahmoud Mohamed Mokhtar

2017-06-01

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

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.

Beneficial and adverse effects of chemopreventive agents

International Nuclear Information System (INIS)

Lee, Byung Mu; Park, Kwang-Kyun

2003-01-01

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

Chemoprevention of skin cancer by the flavonoid fraction of Saraca asoka.

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Cibin, T R; Devi, D Gayathri; Abraham, Annie

2010-05-01

Saraca asoka (Family - Caesalpiniaceae) has been widely used in the Ayurvedic (traditional Indian) system of medicine especially due to its wound healing property. The present study investigated the chemopreventive property of flavonoids from the flowers of Saraca asoka on 7,12 dimethyl benz(a)anthracene (DMBA) induced skin cancer in mice models. A single topical application of DMBA (100 microg/50 microL of acetone) followed after 2 weeks by three times a week treatment with croton oil (1% in acetone), for 20 weeks resulted in tumor induction. The topical application of the flavonoid fraction of S. asoka (FF S. asoka), 30 min prior to the application of croton oil thrice weekly for 20 weeks, caused a significant reduction in the number of tumors per mouse and the percentage of tumor-bearing mice. Also the latency period for the appearance of the first tumor was delayed by S. asoka pretreatment. In the flavonoid fraction (5 mg and 10 mg/kg body weight) treated animals, the levels of biochemical markers - rhodanese, myeloperoxidase, beta-D-glucuronidase, sialic acid, hexokinase and caspase 3 were significantly restored to near normal levels. These findings suggest the chemopreventive activity of flavonoids from S. asoka on two stage skin carcinogenesis. Histological data also support the chemopreventive potential of S. asoka. Copyright (c) 2009 John Wiley & Sons, Ltd.

Trimethoxy-resveratrol and piceatannol administered orally suppress and inhibit tumor formation and growth in prostate cancer xenografts

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Resveratrol (Res) is recognized as a promising cancer chemoprevention dietary polyphenol with antioxidative, anti-inflammatory and anticancer properties. However, the role of its analogues in prostate cancer (PCa) chemoprevention is still unknown. METHODS. We synthesized natural and synthetic anal...

Nanoemulsions of cancer chemopreventive agent benzyl isothiocyanate display enhanced solubility, dissolution, and permeability.

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Qhattal, Hussaini Syed Sha; Wang, Shu; Salihima, Tri; Srivastava, Sanjay K; Liu, Xinli

2011-12-14

Benzyl isothiocyanate (BITC), a compound found in cruciferous vegetables, is an effective chemopreventive agent. The objective of this study was to develop nanoemulsion formulations for the oral delivery of BITC. Optimized oil-in-water BITC nanoemulsions were prepared by a spontaneous self-nanoemulsification method and a homogenization-sonication method. Both nanoemulsions entrapped high amounts of BITC (15-17 mg/mL), with low polydispersity and good colloidal stability. The BITC nanoemulsions showed enhanced solubility and dissolution compared to pure BITC. These formulations markedly increased the apical to basolateral transport of BITC in Caco-2 cell monolayers. The apparent permeability values were 3.6 × 10(-6) cm/s for pure BITC and (1.1-1.3) × 10(-5) cm/s for BITC nanoemulsions. The nanoemulsions were easily taken up by human cancer cells A549 and SKOV-3 and inhibited tumor growth in vitro. This work shows for the first time that BITC can be formulated into nanoemulsions and may show promise in enhancing absorption and bioavailability.

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

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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

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

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Prasan R. Bhandari

2015-04-01

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

New perspectives of curcumin in cancer prevention

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Park, Wungki; Amin, A.R.M Ruhul; Chen, Zhuo Georgia; Shin, Dong M.

2013-01-01

Numerous natural compounds have been extensively investigated for their potential for cancer prevention over decades. Curcumin, from Curcuma longa, is a highly promising natural compound that can be potentially used for chemoprevention of multiple cancers. Curcumin modulates multiple molecular pathways involved in the lengthy carcinogenesis process to exert its chemopreventive effects through several mechanisms: promoting apoptosis, inhibiting survival signals, scavenging reactive oxidative species (ROS), and reducing the inflammatory cancer microenvironment. Curcumin fulfills the characteristics for an ideal chemopreventive agent with its low toxicity, affordability, and easy accessibility. Nevertheless, the clinical application of curcumin is currently compromised by its poor bioavailability. Here we review the potential of curcumin in cancer prevention, its molecular targets, and action mechanisms. Finally, we suggest specific recommendations to improve its efficacy and bioavailability for clinical applications. PMID:23466484

Scientific Evidence of Rice By-Products for Cancer Prevention: Chemopreventive Properties of Waste Products from Rice Milling on Carcinogenesis In Vitro and In Vivo

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Bee Ling Tan

2017-01-01

Full Text Available Cancer is a significant global health concern affecting men and women worldwide. Although current chemopreventive drugs could inhibit the growth of cancer cells, they exert many adverse side effects. Dietary factor plays a crucial role in the management of cancers and has drawn the attention of researchers to be used as an option to combat this disease. Both in vitro and in vivo studies showed that rice and its by-products display encouraging results in the prevention of this disease. The mechanism of anticancer effect is suggested partly through potentiation of bioactive compounds like vitamin E, phytic acid, γ-aminobutyric acid (GABA, γ-oryzanol, and phenolics. Nevertheless, the bioactivity of rice and its by-products is still incompletely understood. In this review, we present the findings from a preclinical study both in in vitro and in animal experiments on the promising role of rice by-products with focus on cancer prevention.

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

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Horng-Jyh Tsai

2015-04-01

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

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

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Elsa Quiroz

2016-01-01

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

Chemical carcinogenesis and chemoprevention: Scientific priority ...

African Journals Online (AJOL)

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

Salicylic acid metabolites and derivatives inhibit CDK activity: Novel insights into aspirin's chemopreventive effects against colorectal cancer

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Dachineni, Rakesh; Kumar, D. Ramesh; Callegari, Eduardo; Kesharwani, Siddharth S.; Sankaranarayanan, Ranjini; Seefeldt, Teresa; Tummala, Hemachand; Bhat, G. Jayarama

2017-01-01

Aspirin's potential as a drug continues to be evaluated for the prevention of colorectal cancer (CRC). Although multiple targets for aspirin and its metabolite, salicylic acid, have been identified, no unifying mechanism has been proposed to clearly explain its chemopreventive effects. Our goal here was to investigate the ability of salicylic acid metabolites, known to be generated through cytochrome P450 (CYP450) enzymes, and its derivatives as cyclin dependent kinase (CDK) inhibitors to gain new insights into aspirin's chemopreventive actions. Using in vitro kinase assays, for the first time, we demonstrate that salicylic acid metabolites, 2,3-dihydroxy-benzoic acid (2,3-DHBA) and 2,5-dihydroxybenzoic acid (2,5-DHBA), as well as derivatives 2,4-dihydroxybenzoic acid (2,4-DHBA), 2,6-dihydroxybenzoic acid (2,6-DHBA), inhibited CDK1 enzyme activity. 2,3-DHBA and 2,6-DHBA did not inhibit CDK2 and 4; however, both inhibited CDK-6 activity. Interestingly, another derivative, 2,4,6-trihydroxybenzoic acid (2,4,6-THBA) was highly effective in inhibiting CDK1, 2, 4 and 6 activity. Molecular docking studies showed that these compounds potentially interact with CDK1. Immunoblotting experiments showed that aspirin acetylated CDK1, and pre-incubation with salicylic acid and its derivatives prevented aspirin-mediated CDK1 acetylation, which supported the data obtained from molecular docking studies. We suggest that intracellularly generated salicylic acid metabolites through CYP450 enzymes within the colonic epithelial cells, or the salicylic acid metabolites generated by gut microflora may significantly contribute to the preferential chemopreventive effect of aspirin against CRC through inhibition of CDKs. This novel hypothesis and mechanism of action in aspirin's chemopreventive effects opens a new area for future research. In addition, structural modification to salicylic acid derivatives may prove useful in the development of novel CDK inhibitors in cancer prevention and

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.

Chemoprevention of esophageal squamous cell carcinoma

International Nuclear Information System (INIS)

Stoner, Gary D.; Wang Lishu; Chen Tong

2007-01-01

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

Intrinsic mitochondrial membrane potential change and associated events mediate apoptosis in chemopreventive effect of diclofenac in colon cancer.

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Kaur, Jasmeet; Sanyal, S N

2010-01-01

The present study explored the role of intrinsic mitochondrial membrane potential (delta psi M) in NSAID-induced apoptosis in the early stages of colon cancer. 1,2-Dimethylhydrazine dihydrochloride (DMH) was used to induce colon cancer and its chemoprevention was studied by diclofenac in a rat model. After 6 weeks of treatment with DMH (early stage), morphological analysis revealed a marked occurrence of preneoplastic features [i.e., mucosal plaque lesions (MPLs) in the colonic tissue]. Coadministration of diclofenac with DMH resulted in a significant reduction of these lesions, thereby proving the chemopreventive efficacy of diclofenac at the chosen anti-inflammatory dose. DMH treatment also led to a significant increase in delta psi M in the isolated colonocytes as assessed by JC-1 fluorescent staining, measured both by fluorescence microscopy and spectrofluorometerically. Further, there was seen a reduction in the number of cells showing low delta psi M, and hence monomer intensity of JC-1 by DMH treatment. To study the mechanism of these alterations in delta psi M in the present work, we studied the protein expression of important proapoptotic proteins, cytochrome c and Bax, by Western blot analysis and immunohistochemistry. DMH treatment reduced the mitochondrial translocation of Bax whereas cytochrome c was found to be located prominently in the mitochondria. Protein expression of antiapoptotic Bcl-2 was also studied in the colonic mucosa, which was expectedly found to be overexpressed after DMH treatment. Diclofenac treatment ameliorated the elevated delta psi M and its associated events to exert its chemopreventive action against early stages of colon cancer.

Evaluation of chemopreventive potential of Strobilanthes crispus against colon cancer formation in vitro and in vivo.

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Al-Henhena, Nawal; Khalifa, Shaden A M; Ying, Rozaida Poh Yuen; Ismail, Salmah; Hamadi, Riad; Shawter, Abdrabu N; Idris, Azila Mohd; Azizan, Ainnul; Al-Wajeeh, Nahla Saeed; Abdulla, Mahmood Ameen; El-Seedi, Hesham R

2015-11-25

With cancer being one of the major causes of death around the world, studies are ongoing to find new chemotherapeutic leads. There are common mechanisms for colorectal cancer (CRC) formation. Several are connected with oxidative stress-induced cell apoptosis and others are related to imbalanced homeostasis or intake of drugs/toxins. Plants that have been used for decades in folk and traditional medicine have been accepted as one of the commonest sources of discovered natural agents of cancer chemotherapy and chemoprevention. The aim was to study the antioxidant and chemopreventive effects of Strobilanthes crispus on colorectal cancer formation. Five groups of rats were injected subcutaneously with AOM, 15 mg/kg body weight, each once weekly for 2 weeks. The cancer group was continued on 10 % Tween-20 feeding for 8 weeks. The standard drug group was continued on 35 mg/kg 5-fluorouracil intraperitoneal injection twice a week for 8 weeks, and the experimental groups were continued on 250 and 500 mg/kg S. crispus extract oral feeding for 8 weeks, respectively. The normal group was injected subcutaneously with normal saline once a week for 2 weeks, followed by oral administration of 10 % Tween-20 for 8 weeks. All the rats were sacrificed after 10 weeks. The colons were evaluated grossly and histopathologically for aberrant crypt foci (ACF). Gene expression was performed for Bax, Bcl2, Defa24, Slc24a3, and APC genes by real-time PCR. S. crispus and its fractions were evaluated for their chemopreventive effects against human colorectal adenocarcinoma cell line HT29 and cytotoxicity for normal human colon epithelial cell line CCD 841, and the active fraction was assessed for its components. We observed significant decrease in total colonic ACF formation, malonaldehyde (MDA) and lactate dehydrogenase (LDH), increase in superoxide dismutase (SOD), up-regulation of APC, Bax and Slc24a3, and down-regulation of Defa24 and Bcl-2 in rats treated with Strobilanthes

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

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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.

Intrinsic fluorescence biomarkers in cells treated with chemopreventive drugs

Science.gov (United States)

Kirkpatrick, Nathaniel D.; Brands, William R.; Zou, Changping; Brewer, Molly A.; Utzinger, Urs

2005-03-01

Non-invasive monitoring of cellular metabolism offers promising insights into areas ranging from biomarkers for drug activity to cancer diagnosis. Fluorescence spectroscopy can be utilized in order to exploit endogenous fluorophores, typically metabolic co-factors nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD), and estimate the redox status of the sample. Fluorescence spectroscopy was applied to follow metabolic changes in epithelial ovarian cells as well as bladder epithelial cancer cells during treatment with a chemopreventive drug that initiates cellular quiescence. Fluorescence signals consistent with NADH, FAD, and tryptophan were measured to monitor cellular activity, redox status, and protein content. Cells were treated with varying concentrations of N-4-(hydroxyphenyl) retinamide (4-HPR) and measured in a stable environment with a sensitive fluorescence spectrometer. A subset of measurements was completed on a low concentration of cells to demonstrate feasibility for medical application such as in bladder or ovary washes. Results suggest that all of the cells responded with similar dose dependence but started at different estimated redox ratio baseline levels correlating with cell cycle, growth inhibition, and apoptosis assays. NADH and tryptophan related fluorescence changed significantly while FAD related fluorescence remained unaltered. Fluorescence data collected from approximately 1000 - 2000 cells, comparable to a bladder or ovary wash, was measurable and useful for future experiments. This study suggests that future intrinsic biomarker measurements may need to be most sensitive to changes in NADH and tryptophan related fluorescence while using FAD related fluorescence to help estimate the baseline redox ratio and predict response to chemopreventive agents.

Oral Carcinogenesis and Oral Cancer Chemoprevention: A Review

OpenAIRE

Tanaka, Takuji; Tanaka, Mayu; Tanaka, Takahiro

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...

The 4Ps of Breast Cancer Chemoprevention: Putting Proven Principles into Practice.

Science.gov (United States)

Jordan, V Craig

2017-04-01

The pioneering Royal Marsden Tamoxifen Prevention Trial recruited 2,471 eligible high-risk women to be randomized to either placebo or tamoxifen (20 mg daily) for 8 years. Breast cancer incidence was evaluated at a median of 18.4 years from the start of the study. There was a 32% reduction in estrogen/progesterone receptor (ER/PR)-positive breast cancers after tamoxifen treatment finished. Translational research, to study "the good, the bad, and the ugly of tamoxifen" in the 1980s, subsequently ensured women's safety from possible increases in osteoperosis, coronary heart disease, and endometrial cancer. Other tamoxifen chemoprevention trials followed. The result of laboratory research was the unanticipated discovery of raloxifene to prevent osteoporosis and breast cancer at the same time. A new group of medicines, now known as selective ER modulators, was established. Indeed, the ability to prevent or delay multiple diseases with a single cheap medicine has the potential to alleviate pressure on health care systems that are overwhelmed. It is a priority to educate physicians appropriately to apply recommended proven medicines as preventives. Cancer Prev Res; 10(4); 219-22. ©2017 AACR See related article by Detre, et al., Cancer Prev Res 2017;10(3):171-6 . ©2017 American Association for Cancer Research.

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. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A review of the dietary flavonoid, kaempferol on human health and cancer chemoprevention

Science.gov (United States)

Chen, Allen Y.; Chen, Yi Charlie

2013-01-01

Kaempferol is a polyphenol antioxidant found in fruits and vegetables. Many studies have described the beneficial effects of dietary kaempferol in reducing the risk of chronic diseases, especially cancer. Epidemiological studies have shown an inverse relationship between kaempferol intake and cancer. Kaempferol may help by augmenting the body’s antioxidant defense against free radicals, which promote the development of cancer. At the molecular level, kaempferol has been reported to modulate a number of key elements in cellular signal transduction pathways linked to apoptosis, angiogenesis, inflammation, and metastasis. Significantly, kaempferol inhibits cancer cell growth and angiognesis and induces cancer cell apoptosis, but on the other hand, kaempferol appears to preserve normal cell viability, in some cases exerting a protective effect. The aim of this review is to synthesize information concerning the extraction of kaempferol, as well as to provide insights into the molecular basis of its potential chemo-preventative activities, with an emphasis on its ability to control intracellular signaling cascades that regulate the aforementioned processes. Chemoprevention using nanotechnology to improve the bioavailability of kaempferol is also discussed. PMID:23497863

Combination Chemoprevention with Grape Antioxidants

OpenAIRE

Singh, Chandra K.; Siddiqui, Imtiaz A.; El-Abd, Sabah; Mukhtar, Hasan; Ahmad, Nihal

2016-01-01

Antioxidant ingredients present in grape have been extensively investigated for their cancer chemopreventive effects. However, much of the work has been done on individual ingredients, especially focusing on resveratrol and quercetin. Phytochemically, whole grape represents a combination of numerous phytonutrients. Limited research has been done on the possible synergistic/additive/antagonistic interactions among the grape constituents. Among these phytochemical constituents of grapes, resver...

Skp2 is a Promising Therapeutic Target in Breast Cancer

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Wang, Zhiwei; Fukushima, Hidefumi; Inuzuka, Hiroyuki; Wan, Lixin; Liu, Pengda; Gao, Daming [Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (United States); Sarkar, Fazlul H. [Department of Pathology, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI (United States); Wei, Wenyi, E-mail: wwei2@bidmc.harvard.edu [Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (United States)

2012-01-04

Breast cancer is the most common type of cancer among American women, and remains the second leading cause of cancer-related death for female in the United States. It has been known that several signaling pathways and various factors play critical roles in the development and progression of breast cancer, such as estrogen receptor, Notch, PTEN, human epidermal growth factor receptor 2, PI3K/Akt, BRCA1, and BRCA2. Emerging evidence has shown that the F-box protein S-phase kinase associated protein 2 (Skp2) also plays an important role in the pathogenesis of breast cancer. Therefore, in this brief review, we summarize the novel functions of Skp2 in the pathogenesis of breast cancer. Moreover, we provide further evidence regarding the state of our knowledge toward the development of novel Skp2 inhibitors especially natural “chemopreventive agents” as targeted approach for the prevention and/or treatment of breast cancer.

Proteomic Profiling Reveals That Resveratrol Inhibits HSP27 Expression and Sensitizes Breast Cancer Cells to Doxorubicin Therapy

OpenAIRE

D?az-Ch?vez, Jos?; Fonseca-S?nchez, Miguel A.; Arechaga-Ocampo, Elena; Flores-P?rez, Ali; Palacios-Rodr?guez, Yadira; Dom?nguez-G?mez, Guadalupe; Marchat, Laurence A.; Fuentes-Mera, Lizeth; Mendoza-Hern?ndez, Guillermo; Gariglio, Patricio; L?pez-Camarillo, C?sar

2013-01-01

The use of chemopreventive natural compounds represents a promising strategy in the search for novel therapeutic agents in cancer. Resveratrol (3,4',5-trans-trihydroxystilbilene) is a dietary polyphenol found in fruits, vegetables and medicinal plants that exhibits chemopreventive and antitumor effects. In this study, we searched for modulated proteins with preventive or therapeutic potential in MCF-7 breast cancer cells exposed to resveratrol. Using two-dimensional electrophoresis we found s...

Resveratrol: Chemoprevention with red wine

OpenAIRE

Arısan, Elif Damla; Palavan-Ünsal, Narçin

2007-01-01

According to epidemiological studies, western diet has disadvantages because of cancer prevalence more than Mediterranean or Asia people who consume more vegetables and fruits. Resveratrol (trans-3,4,5-trihydroxystilbene) which is highly found in grapes, berries has received attention for its potential chemopreventive and antitumor effects in experimental systems. Because of high resveratrol content, researchers noted that red wine has multidimensional benefits for ...

Inhibition of Pro-inflammatory and Anti-apoptotic Biomarkers during Experimental Oral Cancer Chemoprevention by Dietary Black Raspberries

Directory of Open Access Journals (Sweden)

Steve Oghumu

2017-10-01

Full Text Available Oral cancer continues to be a significant public health problem worldwide. Recently conducted clinical trials demonstrate the ability of black raspberries (BRBs to modulate biomarkers of molecular efficacy that supports a chemopreventive strategy against oral cancer. However, it is essential that a preclinical animal model of black raspberry (BRB chemoprevention which recapitulates human oral carcinogenesis be developed, so that we can validate biomarkers and evaluate potential mechanisms of action. We therefore established the ability of BRBs to inhibit oral lesion formation in a carcinogen-induced rat oral cancer model and examined potential mechanisms. F344 rats were administered 4-nitroquinoline 1-oxide (4NQO (20 µg/ml in drinking water for 14 weeks followed by regular drinking water for 6 weeks. At week 14, rats were fed a diet containing either 5 or 10% BRB, or 0.4% ellagic acid (EA, a BRB phytochemical. Dietary administration of 5 and 10% BRB reduced oral lesion incidence and multiplicity by 39.3 and 28.6%, respectively. Histopathological analyses demonstrate the ability of BRBs and, to a lesser extent EA, to inhibit the progression of oral cancer. Oral lesion inhibition by BRBs was associated with a reduction in the mRNA expression of pro-inflammatory biomarkers Cxcl1, Mif, and Nfe2l2 as well as the anti-apoptotic and cell cycle associated markers Birc5, Aurka, Ccna1, and Ccna2. Cellular proliferation (Ki-67 staining in tongue lesions was inhibited by BRBs and EA. Our study demonstrates that, in the rat 4NQO oral cancer model, dietary administration of BRBs inhibits oral carcinogenesis via inhibition of pro-inflammatory and anti-apoptotic pathways.

Chemoprevention utility of silibinin and Cdk4 pathway inhibition in Apc−/+ mice

International Nuclear Information System (INIS)

Karim, Baktiar O; Rhee, Ki-Jong; Liu, Guosheng; Zheng, Dongfeng; Huso, David L

2013-01-01

Colorectal cancer (CRC) is the second leading cause of death from cancer in the United States. Colorectal cancers have a prolonged latency following initiation that may span decades providing ample time for implementing a chemoprevention strategy that could block or reverse the progression to CRC. Cdk4 pathway alterations have been linked to a number of cancers including CRC. In these experiments we focused on the Cdk4 pathway and its role in intestinal tumorigenesis as a possible target in chemoprevention strategies. We evaluated the effect of Cdk4 blockade on the prevention of intestinal tumor formation by crossing Cdk4 −/− mice to Apc −/+ mice. In addition, we tested the effect of the dietary compound silibinin on the Cdk4 pathway in Apc −/+ mice and HT-29 colon cancer cells in culture. Cdk4 −/− mice backcrossed to Apc −/+ mice reduced intestinal adenoma formation compared to Apc −/+ controls. Silibinin effectively targeted the Cdk4 pathway causing hypophosphorylation of the retinoblastoma protein, inhibited cell growth, and induced apoptosis. As a result silibinin blocked the development of intestinal adenomas by 52% in this genetic model (Apc −/+ mice) of early events in colorectal cancer formation. No toxic abnormalities were detected in mice which received silibinin. Modification of the Cdk4 pathway using a natural plant-derived compound such as silibinin may be a useful chemopreventive strategy for colorectal carcinomas

Chemoprevention by WR-2721

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

1993-05-01

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

Chemoprevention by WR-2721

Energy Technology Data Exchange (ETDEWEB)

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

1993-01-01

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

Phase 0 Clinical Chemoprevention Trial of the AKT Inhibitor SR13668

Science.gov (United States)

Reid, Joel M.; Walden, Chad; Qin, Rui; Allen Ziegler, Katie L.; Haslam, John L.; Rajewski, Roger A.; Warndahl, Roger; Fitting, Cindy L.; Boring, Daniel; Szabo, Eva; Crowell, James; Perloff, Marjorie; Jong, Ling; Mandrekar, Sumithra J.; Ames, Matthew M.; Limburg, Paul J.

2011-01-01

Purpose SR13668, an orally active AKT pathway inhibitor, has demonstrated cancer chemopreventive potential in preclinical studies. To accelerate the clinical development of this promising agent, we designed and conducted the first-ever phase 0 chemoprevention trial to evaluate and compare the effects of food and formulation on SR13668 bioavailability. Patients and Methods Healthy adult volunteers were randomly assigned to receive a single, 38 mg oral dose of SR13668 in one of five different formulations, with or without food. Based on existing animal data, SR13668 in a PEG400/Labrasol® oral solution was defined as the reference formulation. Blood samples were obtained pre- and post-agent administration for pharmacokinetic analyses. Area under the plasma concentration-time curve (AUC0-∞) was defined as the primary endpoint. Data were analyzed and compared using established statistical methods for phase 0 trials with a limited sample size. Results Participants (N=20) were rapidly accrued over a 5-month period. Complete pharmacokinetic data were available for 18 randomized participants. AUC0-∞ values were highest in the fed state (range = 122–439 ng/mL × hours) and were statistically significantly different across formulations (p = 0.007), with Solutol® HS15 providing the highest bioavailability. SR13668 time to peak plasma concentration (3 hours; range, 2 – 6 hours) and half-life were (11.2 ± 3.1 hours) were not formulation dependent. Conclusions Using a novel, highly efficient study design, we rapidly identified a lead formulation of SR13668 for further clinical testing. Our findings support application of the phase 0 trial paradigm to accelerate chemoprevention agent development. PMID:21372034

Evaluation of sestamibi scanning as a predictor of risk of development of breast cancer and as a non-invasive biomarker for breast cancer chemoprevention trials

International Nuclear Information System (INIS)

Kimler, B.F.; Preston, D.; McMillin, C.H.; Dusing, R.; Zalles, C.M.; Fabian, C.J.

2003-01-01

Sestamibi scintimammography is becoming increasingly accepted as an adjunct to conventional breast imaging by mammography and ultrasound. We sought to determine whether it might serve to detect/quantify pre-cancerous breast lesions, specifically hyperplasia with atypia which, when detected by random periareolar fine needle aspiration (FNA), is known to be associated with increased risk for subsequent development of breast cancer. If a parameter derived from sestamibi scanning could be shown to correlate with and predict for atypia, then this could serve 1) to refine estimates of risk of development of breast cancer; and 2) as a surrogate endpoint biomarker in clinical breast cancer chemoprevention trials. To this end, we performed sestamibi scanning on both breasts of 65 women at high risk for development of breast cancer who also underwent FNA. Seventeen women (26%) exhibited non-proliferative cytology; 30 (46%) had hyperplasia; and 18 (28%) had hyperplasia with atypia in the FNA specimen. Since the fine needle aspiration specimens from both breasts are pooled to provide a single result, we likewise pooled the sestamibi results from both breasts so as to consider the most abnormal finding. Twenty-five women (39%) were characterized as having an abnormal sestamibi scan with heterogenous, focal, intense uptake. There was no correlation between an abnormal scan and cytologic evidence of hyperplasia with atypia. Neither was there a correlation between any of a variety of quantitative measures of the sestamibi scans and the cytological classification. At this time, there is no indication for the use of sestamibi scanning for the prediction of risk of subsequent development of breast cancer, or as a surrogate endpoint biomarker in clinical breast cancer chemoprevention trials

Chemopreventive Effect of Aster glehni on Inflammation-Induced Colorectal Carcinogenesis in Mice

Directory of Open Access Journals (Sweden)

Kyung-Sook Chung

2018-02-01

Full Text Available Although Aster glehni is a common dietary herb that has various bioactivities, including anti-diabetic, anti-adipogenic, and anti-inflammatory effects, A. glehni has not been studied in colon cancer. Therefore, we hypothesized the chemopreventive effects of an ethanol extract of A. glehni (AG on azoxymethane/dextran sulfate sodium (AOM/DSS-induced colitis-associated cancer (CAC in mice. In this study, we found that treatment with AG significantly attenuated the AOM/DSS-induced enlargement of the spleen and shortening of the colon. In addition, colonic tumor formation, colonic damage, and increased muscle thickness were significantly reduced in AOM/DSS-induced mice fed AG. Treatment with AG also reduced intestinal interleukin (IL-1β, IL-6, and tumor necrosis factor (TNF-α production and decreased inducible nitric oxide synthase (iNOS and cyclooxygenase (COX-2 protein expression in mice with AOM/DSS-induced CAC. Furthermore, AG reduced nuclear factor (NF-κB activation via phosphorylation and degradation of inhibitor of kappa Bα (IκBα, leading to inhibition of NF-κB p65 nuclear translocation. It also downregulated the expression of NF-κB-related proteins, including the B-cell lymphoma 2 (Bcl-2 family and inhibitors of apoptosis proteins (IAPs, in mice with AOM/DSS-induced CAC. Taken together, these findings suggest that the treatment with AG inhibited colitis-associated colon carcinogenesis in mice, and this chemopreventive effect was strongly mediated by suppression of the NF-κB signaling pathway, indicating that AG could be a promising protective agent against CAC.

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

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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

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

Science.gov (United States)

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

2014-01-01

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

The beta-carotene and retinol efficacy trial (CARET) for chemoprevention of lung cancer in high risk populations: smokers and asbestos-exposed workers.

Science.gov (United States)

Omenn, G S; Goodman, G; Thornquist, M; Grizzle, J; Rosenstock, L; Barnhart, S; Balmes, J; Cherniack, M G; Cullen, M R; Glass, A

1994-04-01

CARET is a multicenter, two-armed, double-masked randomized chemoprevention trial in Seattle, Portland, San Francisco, Baltimore, Connecticut, and Irvine, to test whether oral administration of beta-carotene (30 mg/day) plus retinyl palmitate (25,000 IU/day) can decrease the incidence of lung cancer in high risk populations, namely, heavy smokers and asbestos-exposed workers. The intervention combines the antioxidant action of beta-carotene and the tumor suppressor mechanism of vitamin A. As of April 30, 1993, CARET had randomized 1,845 participants in the 1985-1988 pilot phase plus 13,260 "efficacy" participants since 1989; of these, 4,000 are asbestos-exposed males and 11,105 are smokers and former smokers (44% female). Accrual is complete everywhere except Irvine, which was the last center added (1991), and the safety profile of the regimen to date has been excellent. With 14,420 smokers, 4,010 asbestos-exposed participants, and 114,100 person-years through February 1998, we expect CARET to be capable of detecting a 23% reduction in lung cancer incidence in the two populations combined and 27, 49, 32, and 35% reductions in the smokers, female smokers, male smokers, and asbestos-exposed subgroups, respectively. CARET is highly complementary to the alpha-tocopherol-beta-carotene study in Finland and the Harvard Physicians Health Study (beta-carotene alone) in the National Cancer Institute portfolio of major cancer chemoprevention trials.

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

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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.

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

Energy Technology Data Exchange (ETDEWEB)

Nguyen, Carvell T.; Isariyawongse, Brandon [Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation, Cleveland, OH (United States); Yu, Changhong; Kattan, Michael W., E-mail: kattanm@ccf.org [Department of Quantitative Health Sciences, Cleveland Clinic Foundation, Cleveland, OH (United States)

2012-10-11

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 biopsy cohort, Cox proportional hazards (PH) and competing risks regression (CRR) models were used to build 18 nomograms, whose predictive ability was measured by concordance index (CI) 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.

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

International Nuclear Information System (INIS)

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

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 biopsy cohort, Cox proportional hazards (PH) and competing risks regression (CRR) models were used to build 18 nomograms, whose predictive ability was measured by concordance index (CI) 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.

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

International Nuclear Information System (INIS)

Ahmad, Shiekh Tanveer; Arjumand, Wani; Seth, Amlesh; Nafees, Sana; Rashid, Summya; Ali, Nemat; Sultana, Sarwat

2011-01-01

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

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.

Anti-inflammatory, antiproliferative, and cytoprotective activity of NO chimera nitrates of use in cancer chemoprevention.

Science.gov (United States)

Hagos, Ghenet K; Abdul-Hay, Samer O; Sohn, Johann; Edirisinghe, Praneeth D; Chandrasena, R Esala P; Wang, Zhiqiang; Li, Qian; Thatcher, Gregory R J

2008-11-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown promise in colorectal cancer (CRC), but they are compromised by gastrotoxicity. NO-NSAIDs are hybrid nitrates conjugated to an NSAID designed to exploit the gastroprotective properties of NO bioactivity. The NO chimera ethyl 2-((2,3-bis(nitrooxy)propyl)disulfanyl)benzoate (GT-094), a novel nitrate containing an NSAID and disulfide pharmacophores, is effective in vivo in rat models of CRC and is a lead compound for design of agents of use in CRC. Preferred chemopreventive agents possess 1) antiproliferative and 2) anti-inflammatory actions and 3) the ability to induce cytoprotective phase 2 enzymes. To determine the contribution of each pharmacophore to the biological activity of GT-094, these three biological activities were studied in vitro in compounds that deconstructed the structural elements of the lead GT-094. The anti-inflammatory and antiproliferative actions of GT-094 in vivo were recapitulated in vitro, and GT-094 was seen to induce phase 2 enzymes via the antioxidant responsive element. In the variety of colon, macrophage-like, and liver cell lines studied, the evidence from structure-activity relationships was that the disulfide structural element of GT-094 is the dominant contributor in vitro to the anti-inflammatory activity, antiproliferation, and enzyme induction. The results provide a direction for lead compound refinement. The evidence for a contribution from the NO mimetic activity of nitrates in vitro was equivocal, and combinations of nitrates with acetylsalicylic acid were inactive.

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

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Paulraj Gabriel M

2010-06-01

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

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

Science.gov (United States)

2010-01-01

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

Study on the interaction of chemopreventive compounds and food born carcinogens with cytochrome P450 enzymes

OpenAIRE

Brabencová, Eliška

2013-01-01

The use of food supplements containing natural chemopreventive compounds increased in recent years. Some of the most popular chemopreventive compounds are flavonoids. Due to their natural origin, flavonoids are generally accepted as safe compounds. They exert antioxidant, anti-cancer and anti-inflammatory properties. However, flavonoids should be considered as foreign compounds (xenobiotics). Flavonoids interact with many enzymes, among the most important belong cytochromes P450 (CYPs), key e...

Chemopreventive Effects of Germinated Rough Rice Crude Extract in Inhibiting Azoxymethane-Induced Aberrant Crypt Foci Formation in Sprague-Dawley Rats

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Elnaz Saki

2017-01-01

Full Text Available Chemoprevention has become an important area in cancer research due to low success rate of current therapeutic modalities. Diet plays a vital role in the etiology of cancer. This research was carried out to study the chemopreventive properties of germinated rough rice (GRR crude extract in Sprague-Dawley rats induced with azoxymethane. Germination of rough rice causes significant changes in several chemical compositions of presently bioactive compounds. These compounds may prevent or postpone the inception of cancer. Fifty male Sprague-Dawley rats (6 weeks of age were randomly divided into 5 groups which were (G1 induced with azoxymethane (AOM and not given GRR (positive control, (G2 induced with AOM and given 2000 mg/kg GRR, (G3 induced with AOM and given 1000 mg/kg GRR, (G4 induced with AOM and given 500 mg/kg GRR, and (G5 not induced with AOM and not given GRR crude extract (negative control. To induce colon cancer, rats received two IP injections of AOM in saline (15 mg/kg for two subsequent weeks. Organs were removed and weighed. Aberrant crypt foci (ACF were evaluated histopathologically. β-Catenin expressions were determined by Western blot. Treatment with 2000 mg/kg GRR crude extract not only resulted in the greatest reduction in the size and number of ACF but also displayed the highest percentage of nondysplastic ACF. Treatment with 2000 mg/kg GRR also gave the lowest level of expression in β-catenin. Thus, GRR could be a promising dietary supplement for prevention of CRC.

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

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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.

Application Instructions | 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

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.

Chemopreventive and therapeutic activity of dietary blueberry against estrogen-mediated breast cancer.

Science.gov (United States)

Jeyabalan, Jeyaprakash; Aqil, Farrukh; Munagala, Radha; Annamalai, Lakshmanan; Vadhanam, Manicka V; Gupta, Ramesh C

2014-05-07

Berries are gaining increasing importance lately for their chemopreventive and therapeutic potential against several cancers. In earlier studies, a blueberry-supplemented diet has shown protection against 17β-estradiol (E2)-mediated mammary tumorigenesis. This study tested both preventive and therapeutic activities of diet supplemented with whole blueberry powder (50:50 blend of Tifblue and Rubel). Animals received 5% blueberry diet, either 2 weeks prior to or 12 weeks after E2 treatment in preventive and therapeutic groups, respectively. Both interventions delayed the tumor latency for palpable mammary tumors by 28 and 37 days, respectively. Tumor volume and multiplicity were also reduced significantly in both modes. The effect on mammary tumorigenesis was largely due to down-regulation of CYP 1A1 and ER-α gene expression and also favorable modulation of microRNA (miR-18a and miR-34c) levels. These data suggest that the blueberry blend tested is effective in inhibiting E2-mediated mammary tumorigenesis in both preventive and therapeutic modes.

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

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Yi-Nong Niu

2016-01-01

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

Epigallocatechin Gallate Nanodelivery Systems for Cancer Therapy

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Andreia Granja

2016-05-01

Full Text Available Cancer is one of the leading causes of morbidity and mortality all over the world. Conventional treatments, such as chemotherapy, are generally expensive, highly toxic and lack efficiency. Cancer chemoprevention using phytochemicals is emerging as a promising approach for the treatment of early carcinogenic processes. (−-Epigallocatechin-3-gallate (EGCG is the major bioactive constituent in green tea with numerous health benefits including anti-cancer activity, which has been intensively studied. Besides its potential for chemoprevention, EGCG has also been shown to synergize with common anti-cancer agents, which makes it a suitable adjuvant in chemotherapy. However, limitations in terms of stability and bioavailability have hampered its application in clinical settings. Nanotechnology may have an important role in improving the pharmacokinetic and pharmacodynamics of EGCG. Indeed, several studies have already reported the use of nanoparticles as delivery vehicles of EGCG for cancer therapy. The aim of this article is to discuss the EGCG molecule and its associated health benefits, particularly its anti-cancer activity and provide an overview of the studies that have employed nanotechnology strategies to enhance EGCG’s properties and potentiate its anti-tumoral activity.

Diet and prostate cancer - a holistic approach to management.

Science.gov (United States)

Cheetham, Philippa J; Katz, Aaron E

2011-10-01

There is now increasing evidence from epidemiologic surveys and from laboratory, intervention, and case-control studies that diet and lifestyle plays a crucial role in prostate cancer biology and tumorigenesis. This applies to both the development and progression of prostate cancer, although in many cases the specific initiating factors in the diet are poorly understood. Conversely, many nutrients and herbs also show significant promise in helping to treat prostate cancer by slowing progression and reducing recurrence, ultimately reducing the risk of morbidity and mortality from the disease. Furthermore for all grades of prostate cancer, nutritional interventions complement conventional treatment to improve response and quality of life. Slowing or even reversing the progression of, high-grade prostate intraepithelial neoplasia [HGPIN]). with chemo-preventative agents could be the best primary defense against prostate cancer, preventing it from occurring in the first place. The information given in this review about prostate cancer chemoprevention summarizes the key evidence for the role of different dietary components and their effect on prostate cancer prevention and progression. Most nutritional chemoprevention agents also have the added benefit of being beneficial for the cardiovascular system, bone health and for the prevention of other cancers.

Chemopreventive Potential of Powdered Red Wine Pomace Seasonings against Colorectal Cancer in HT-29 Cells.

Science.gov (United States)

Del Pino-García, Raquel; Rivero-Pérez, María D; González-SanJosé, María L; Ortega-Heras, Miriam; García Lomillo, Javier; Muñiz, Pilar

2017-01-11

This study evaluates the antiproliferative and antigenotoxic actions of powdered red wine pomace seasonings (Sk-S, seedless; W-S, whole; Sd-S, seeds). In vitro gastrointestinal digested and colonic fermented fractions of the seasonings were used as cell treatments. Phenolic acids from Sk-S showed the highest bioaccessibility in the small intestine, whereas polyphenols contained in Sd-S might be the most fermentable in the colon. Dietary fiber from Sk-S was the best substrate for short chain fatty acids production by gut microbiota. Colon cancerous (HT-29) cell viability was inhibited by 50% (IC 50 values) at treatment concentrations ranging from 845 (Sk-S) to 1085 (Sd-S) μg/mL prior digestion, but all digested fractions exhibited similar antiproliferative activities (mean IC 50 = 814 μg/mL). Oxidative DNA damage in cells was also attenuated by the treatments (200 μg/mL, 24 h preincubation), with all colonic fermented fractions displaying similar genoprotective action. These results suggest the potential of red wine pomace seasonings as chemopreventive agents in colorectal cancer.

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

Chemoprevention of colorectal cancer by black raspberry anthocyanins involved the modulation of gut microbiota and SFRP2 demethylation.

Science.gov (United States)

Chen, Lili; Jiang, Bowen; Zhong, Chunge; Guo, Jun; Zhang, Lihao; Mu, Teng; Zhang, Qiuhua; Bi, Xiuli

2018-03-08

Freeze-dried black raspberry (BRB) powder is considered as a potential cancer chemopreventive agent. In this study, we fed azoxymethane (AOM)/dextran sodium sulfate (DSS)-treated C57BL/6J mice with a diet containing BRB anthocyanins for 12 weeks, and this led to a reduction in colon carcinogenesis. These animals had consistently lower tumor multiplicity compared with AOM/DSS-treated mice not receiving BRB anthocyanins. In AOM/DSS-treated mice, the number of pathogenic bacteria, including Desulfovibrio sp. and Enterococcus spp., was increased significantly, whereas probiotics such as Eubacterium rectale, Faecalibacterium prausnitzii and Lactobacillus were dramatically decreased, but BRB anthocyanins supplement could reverse this imbalance in gut microbiota. BRB anthocyanins also caused the demethylation of the SFRP2 gene promoter, resulting in increased expression of SFRP2, both at the mRNA and protein levels. Furthermore, the expression levels of DNMT31 and DNMT3B, as well as of p-STAT3 were downregulated by BRB anthocyanins in these animals. Taken together, these results suggested that BRB anthocyanins could modulate the composition of gut commensal microbiota, and changes in inflammation and the methylation status of the SFRP2 gene may play a central role in the chemoprevention of CRC.

In vitro chemopreventive properties of peptides released from quinoa (Chenopodium quinoa Willd.) protein under simulated gastrointestinal digestion.

Science.gov (United States)

Vilcacundo, Rubén; Miralles, Beatriz; Carrillo, Wilman; Hernández-Ledesma, Blanca

2018-03-01

Because of the continuous and direct interaction between the digestive tract and foods, dietary compounds represent an interesting source of chemopreventive agents for gastrointestinal health. In this study, the influence of a standardized static in vitro gastrointestinal digestion model on the release of peptides with chemopreventive potential from quinoa protein was investigated. Gastroduodenal digests and fractions collected by ultrafiltration were evaluated for their in plate oxygen radical absorbance capacity and in vitro colon cancer cell viability inhibitory activity. Highest effects were observed in the digests obtained during the intestinal phase, with fraction containing peptides 5kDa showing the greatest anti-cancer effects. Seventeen potential bioactive peptides derived from quinoa proteins have been identified. These proteins might be utilized as new ingredients in the development of functional foods or nutraceuticals with the aim of reducing oxidative stress-associated diseases, including cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

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 < 0.001) were not significantly modified by BM or CU. Serum MDA levels increased by 4NQO (P = 0.000) were significantly lowered by CU (P = 0.04) and BM (P = 0.04) during initiation and by CU during post-initiation of carcinogenesis (P = 0.01). CU was more potent than BM during post-initiation of carcinogenesis (P = 0.01). Serum GSH lowered by 4NQO (P = 0.55) was significantly decreased by BM and CU (P < 0.012), with no significant difference between groups receiving BM or CU. Moderate dysplasia was the most advanced dysplasia induced and gingival localization the most frequent. Both BM and CU lowered dysplasia scores, with BM being the most efficient during post-initiation of carcinogenesis (P = 0.001). Ki67, cyclin D1, p63, Bcl2 and p53 expression increased with dysplasia scores. BM showed chemopreventive properties during initiation and post-initiation of oral carcinogenesis, reducing local and general oxidative stress and the intensity of dysplasia

Investigation of nuclear nano-morphology marker as a biomarker for cancer risk assessment using a mouse model

Science.gov (United States)

Bista, Rajan K.; Uttam, Shikhar; Hartman, Douglas J.; Qiu, Wei; Yu, Jian; Zhang, Lin; Brand, Randall E.; Liu, Yang

2012-06-01

The development of accurate and clinically applicable tools to assess cancer risk is essential to define candidates to undergo screening for early-stage cancers at a curable stage or provide a novel method to monitor chemoprevention treatments. With the use of our recently developed optical technology--spatial-domain low-coherence quantitative phase microscopy (SL-QPM), we have derived a novel optical biomarker characterized by structure-derived optical path length (OPL) properties from the cell nucleus on the standard histology and cytology specimens, which quantifies the nano-structural alterations within the cell nucleus at the nanoscale sensitivity, referred to as nano-morphology marker. The aim of this study is to evaluate the feasibility of the nuclear nano-morphology marker from histologically normal cells, extracted directly from the standard histology specimens, to detect early-stage carcinogenesis, assess cancer risk, and monitor the effect of chemopreventive treatment. We used a well-established mouse model of spontaneous carcinogenesis--ApcMin mice, which develop multiple intestinal adenomas (Min) due to a germline mutation in the adenomatous polyposis coli (Apc) gene. We found that the nuclear nano-morphology marker quantified by OPL detects the development of carcinogenesis from histologically normal intestinal epithelial cells, even at an early pre-adenomatous stage (six weeks). It also exhibits a good temporal correlation with the small intestine that parallels the development of carcinogenesis and cancer risk. To further assess its ability to monitor the efficacy of chemopreventive agents, we used an established chemopreventive agent, sulindac. The nuclear nano-morphology marker is reversed toward normal after a prolonged treatment. Therefore, our proof-of-concept study establishes the feasibility of the SL-QPM derived nuclear nano-morphology marker OPL as a promising, simple and clinically applicable biomarker for cancer risk assessment and

Cancer Chemoprevention by Traditional Chinese Herbal Medicine and Dietary Phytochemicals: Targeting Nrf2-Mediated Oxidative Stress/Anti-Inflammatory Responses, Epigenetics, and Cancer Stem Cells

Directory of Open Access Journals (Sweden)

Jong Hun Lee

2013-01-01

Full Text Available Excessive oxidative stress induced by reactive oxygen species (ROS, reactive nitrogen species (RNS, and reactive metabolites of carcinogens alters cellular homeostasis, leading to genetic/epigenetic changes, genomic instability, neoplastic transformation, and cancer initiation/progression. As a protective mechanism against oxidative stress, antioxidant/detoxifying enzymes reduce these reactive species and protect normal cells from endo-/exogenous oxidative damage. The transcription factor nuclear factor-erythroid 2 p45 (NF-E2-related factor 2 (Nrf2, a master regulator of the antioxidative stress response, plays a critical role in the expression of many cytoprotective enzymes, including NAD(PH:quinine oxidoreductase (NQO1, heme oxygenase-1 (HO-1, UDP-glucuronosyltransferase (UGT, and glutathione S-transferase (GST. Recent studies demonstrated that many dietary phytochemicals derived from various vegetables, fruits, spices, and herbal medicines induce Nrf2-mediated antioxidant/detoxifying enzymes, restore aberrant epigenetic alterations, and eliminate cancer stem cells (CSCs. The Nrf2-mediated antioxidant response prevents many age-related diseases, including cancer. Owing to their fundamental contribution to carcinogenesis, epigenetic modifications and CSCs are novel targets of dietary phytochemicals and traditional Chinese herbal medicine (TCHM. In this review, we summarize cancer chemoprevention by dietary phytochemicals, including TCHM, which have great potential as a safer and more effective strategy for preventing cancer.

Nitrates and NO-NSAIDs in Cancer Chemoprevention & Therapy: In Vitro Evidence Querying the NO Donor Functionality

Science.gov (United States)

Dunlap, Tareisha; Abdul-Hay, Samer; Chandrasena, R. Esala P.; Hagos, Ghenet K; Sinha, Vaishali; Wang, Zhiqiang; Wang, Huali; Thatcher, Gregory R. J.

2008-01-01

Properties of the NO-ASA family of NO-donating NSAIDs (NO-NSAIDs), notably NCX 4016 (mNO-ASA) and NCX 4040 (pNO-ASA), reported in more than a hundred publications, have included positive preclinical data in cancer chemoprevention and therapy. Evidence is presented that the antiproliferative, the chemopreventive (antioxidant/electrophile response element (ARE) activation), and the anti-inflammatory activity of NO-ASA in cell cultures is replicated by X-ASA derivatives that are incapable of acting as NO donors. pBr-ASA and mBr-ASA are conisogenic with NO-ASA, but are not NO donors. The biological activity of pNO-ASA is replicated by pBr-ASA; and both pNO-ASA and pBr-ASA are bioactivated to the same quinone methide electrophile. The biological activity of mNO-ASA is replicated by mBr-ASA; mNO-ASA and mBr-ASA are bioactivated to different benzyl electrophiles. The observed activity is likely initiated by trapping of thiol biomolecules by the quinone and benzyl electrophiles, leading to depletion of GSH and modification of Cys-containing sensor proteins. Whereas all NO-NSAIDs containing the same structural “linker” as NCX 4040 and NCX 4016 are anticipated to possess activity resulting from bioactivation to electrophilic metabolites, this expectation does not extend to other linker structures. Nitrates require metabolic bioactivation to liberate NO bioactivity, which is often poorly replicated in vitro, and NO bioactivity provided by NO-NSAIDs in vivo provides proven therapeutic benefits in mitigation of NSAID gastrotoxicity. The in vivo properties of X-ASA drugs await discovery. PMID:18485921

Emerging Cancer Vaccines: The Promise of Genetic Vectors

International Nuclear Information System (INIS)

Aurisicchio, Luigi; Ciliberto, Gennaro

2011-01-01

Therapeutic vaccination against cancer is an important approach which, when combined with other therapies, can improve long-term control of cancer. In fact, the induction of adaptive immune responses against Tumor Associated Antigens (TAAs) as well as innate immunity are important factors for tumor stabilization/eradication. A variety of immunization technologies have been explored in last decades and are currently under active evaluation, such as cell-based, protein, peptide and heat-shock protein-based cancer vaccines. Genetic vaccines are emerging as promising methodologies to elicit immune responses against a wide variety of antigens, including TAAs. Amongst these, Adenovirus (Ad)-based vectors show excellent immunogenicity profile and have achieved immunological proof of concept in humans. In vivo electroporation of plasmid DNA (DNA-EP) is also a desirable vaccine technology for cancer vaccines, as it is repeatable several times, a parameter required for the long-term maintenance of anti-tumor immunity. Recent findings show that combinations of different modalities of immunization (heterologous prime/boost) are able to induce superior immune reactions as compared to single-modality vaccines. In this review, we will discuss the challenges and requirements of emerging cancer vaccines, particularly focusing on the genetic cancer vaccines currently under active development and the promise shown by Ad and DNA-EP heterologous prime-boost

Chemoprevention of DMH-induced rat colon carcinoma initiation by combination administration of piroxicam and C-phycocyanin.

Science.gov (United States)

Saini, Manpreet Kaur; Vaiphei, Kim; Sanyal, Sankar Nath

2012-02-01

Cancer research illustrated that combinatorial studies can provide significant improvement in safety and effectiveness over the monotherapy regimens. A combination of two drugs may restrain precancerous colon polyps, opening a new possible opportunity for chemoprevention of colon cancer. In this context, chemopreventive efficacy of a combination regimen of C-phycocyanin, a biliprotein present in Spirulina platensis, a cyanobacterium, which is a selective cycloxygenase-2 (COX-2) inhibitor and piroxicam, a traditional non-steroidal anti-inflammatory drug was considered in 1,2 dimethylhyadrazine (DMH)-induced colon carcinogenesis in rats. Western blotting, immunohistochemistry, DNA fragmentation, fluorescent staining, PGE(2) enzyme immunoassay, and carrageenan-induced paw edema test were performed along with morphological and histological analysis. DMH treatment showed a rich presence of preneoplastic lesions such as multiple plaque lesions, aberrant crypt foci, and well-characterized dysplasia. These features were reduced with piroxicam and C-phycocyanin administration. The number of apoptotic cells was featured prominently in all the groups compared with DMH. DMH treatment revealed intact high molecular weight genomic DNA with no signs of laddering/DNA fragmentation while it was noticeable significantly in control and DMH + piroxicam + C-phycocyanin. DMH group showed highest COX-2 expression and PGE(2) level in comparison with other groups. Doses of piroxicam and C-phycocyanin used in the present study were established at an anti-inflammatory range. A combination regimen of piroxicam and C-phycocyanin, rather than individually has the much greater potential for reduction of DMH-induced colon cancer development and COX-2 being the prime possible target in such chemoprevention.

Breast cancer prevention.

Science.gov (United States)

Euhus, David M; Diaz, Jennifer

2015-01-01

Breast cancer is the most common cancer in women with 232,670 new cases estimated in the USA for 2014. Approaches for reducing breast cancer risk include lifestyle modification, chemoprevention, and prophylactic surgery. Lifestyle modification has a variety of health benefits with few associated risks and is appropriate for all women regardless of breast cancer risk. Chemoprevention options have expanded rapidly, but most are directed at estrogen receptor positive breast cancer and uptake is low. Prophylactic surgery introduces significant additional risks of its own and is generally reserved for the highest risk women. © 2014 Wiley Periodicals, Inc.

Chemopreventive effect of tadalafil in cisplatin-induced ...

African Journals Online (AJOL)

Summary: Nephrotoxicity remains a common untoward effect of cisplatin therapy with limited effective chemopreventive options available till date. This study aims to evaluate the possible chemopreventive effect and mechanism(s) of action of 2 mgkg-1 and 5 mgkg-1 of Tadalafil in cisplatin-induced nephrotoxic rats. In this ...

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

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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.

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

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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.

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....

Dietary factors and epigenetic regulation for prostate cancer prevention.

Science.gov (United States)

Ho, Emily; Beaver, Laura M; Williams, David E; Dashwood, Roderick H

2011-11-01

The role of epigenetic alterations in various human chronic diseases has gained increasing attention and has resulted in a paradigm shift in our understanding of disease susceptibility. In the field of cancer research, e.g., genetic abnormalities/mutations historically were viewed as primary underlying causes; however, epigenetic mechanisms that alter gene expression without affecting DNA sequence are now recognized as being of equal or greater importance for oncogenesis. Methylation of DNA, modification of histones, and interfering microRNA (miRNA) collectively represent a cadre of epigenetic elements dysregulated in cancer. Targeting the epigenome with compounds that modulate DNA methylation, histone marks, and miRNA profiles represents an evolving strategy for cancer chemoprevention, and these approaches are starting to show promise in human clinical trials. Essential micronutrients such as folate, vitamin B-12, selenium, and zinc as well as the dietary phytochemicals sulforaphane, tea polyphenols, curcumin, and allyl sulfur compounds are among a growing list of agents that affect epigenetic events as novel mechanisms of chemoprevention. To illustrate these concepts, the current review highlights the interactions among nutrients, epigenetics, and prostate cancer susceptibility. In particular, we focus on epigenetic dysregulation and the impact of specific nutrients and food components on DNA methylation and histone modifications that can alter gene expression and influence prostate cancer progression.

Nitrates and NO-NSAIDs in cancer chemoprevention and therapy: in vitro evidence querying the NO donor functionality.

Science.gov (United States)

Dunlap, Tareisha; Abdul-Hay, Samer O; Chandrasena, R Esala P; Hagos, Ghenet K; Sinha, Vaishali; Wang, Zhiqiang; Wang, Huali; Thatcher, Gregory R J

2008-09-01

Properties of the NO-ASA family of NO-donating NSAIDs (NO-NSAIDs), notably NCX 4016 (mNO-ASA) and NCX 4040 (pNO-ASA), reported in more than one hundred publications, have included positive preclinical data in cancer chemoprevention and therapy. Evidence is presented that the antiproliferative, the chemopreventive (antioxidant/electrophile response element (ARE) activation), and the anti-inflammatory activity of NO-ASA in cell cultures is replicated by X-ASA derivatives that are incapable of acting as NO donors. pBr-ASA and mBr-ASA are conisogenic with NO-ASA, but are not NO donors. The biological activity of pNO-ASA is replicated by pBr-ASA; and both pNO-ASA and pBr-ASA are bioactivated to the same quinone methide electrophile. The biological activity of mNO-ASA is replicated by mBr-ASA; mNO-ASA and mBr-ASA are bioactivated to different benzyl electrophiles. The observed activity is likely initiated by trapping of thiol biomolecules by the quinone and benzyl electrophiles, leading to depletion of GSH and modification of Cys-containing sensor proteins. Whereas all NO-NSAIDs containing the same structural "linker" as NCX 4040 and NCX 4016 are anticipated to possess activity resulting from bioactivation to electrophilic metabolites, this expectation does not extend to other linker structures. Nitrates require metabolic bioactivation to liberate NO bioactivity, which is often poorly replicated in vitro, and NO bioactivity provided by NO-NSAIDs in vivo provides proven therapeutic benefits in mitigation of NSAID gastrotoxicity. The in vivo properties of X-ASA drugs await discovery.

The chemopreventive action of bromelain, from pineapple stem (Ananas comosus L.), on colon carcinogenesis is related to antiproliferative and proapoptotic effects.

Science.gov (United States)

Romano, Barbara; Fasolino, Ines; Pagano, Ester; Capasso, Raffaele; Pace, Simona; De Rosa, Giuseppe; Milic, Natasa; Orlando, Pierangelo; Izzo, Angelo A; Borrelli, Francesca

2014-03-01

Colorectal cancer is an important health problem across the world. Here, we investigated the possible antiproliferative/proapoptotic effects of bromelain (from the pineapple stem Ananas comosus L., family Bromeliaceae) in a human colorectal carcinoma cell line and its potential chemopreventive effect in a murine model of colon cancer. Proliferation and apoptosis were evaluated in human colon adenocarcinoma (Caco-2) cells by the (3) H-thymidine incorporation assay and caspase 3/7 activity measurement, respectively. Extracellular signal-related kinase (ERK) and Akt expression were evaluated by Western blot analysis, reactive oxygen species production by a fluorimetric method. In vivo, bromelain was evaluated using the azoxymethane murine model of colon carcinogenesis. Bromelain reduced cell proliferation and promoted apoptosis in Caco-2 cells. The effect of bromelain was associated to downregulation of pERK1/2/total, ERK, and pAkt/Akt expression as well as to reduction of reactive oxygen species production. In vivo, bromelain reduced the development of aberrant crypt foci, polyps, and tumors induced by azoxymethane. Bromelain exerts antiproliferative and proapoptotic effects in colorectal carcinoma cells and chemopreventive actions in colon carcinogenesis in vivo. Bromelain-containing foods and/or bromelain itself may represent good candidates for colorectal cancer chemoprevention. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pomegranate-mediated chemoprevention of experimental hepatocarcinogenesis involves Nrf2-regulated antioxidant mechanisms

Science.gov (United States)

Bishayee, Anupam; Bhatia, Deepak; Thoppil, Roslin J.; Darvesh, Altaf S.; Nevo, Eviatar; Lansky, Ephraim P.

2011-01-01

Hepatocellular carcinoma (HCC), one of the most prevalent and lethal cancers, has shown an alarming rise in the USA. Without effective therapy for HCC, novel chemopreventive strategies may effectively circumvent the current morbidity and mortality. Oxidative stress predisposes to hepatocarcinogenesis and is the major driving force of HCC. Pomegranate, an ancient fruit, is gaining tremendous attention due to its powerful antioxidant properties. Here, we examined mechanism-based chemopreventive potential of a pomegranate emulsion (PE) against dietary carcinogen diethylnitrosamine (DENA)-induced rat hepatocarcinogenesis that mimics human HCC. PE treatment (1 or 10 g/kg), started 4 weeks prior to the DENA challenge and continued for 18 weeks thereafter, showed striking chemopreventive activity demonstrated by reduced incidence, number, multiplicity, size and volume of hepatic nodules, precursors of HCC. Both doses of PE significantly attenuated the number and area of γ-glutamyl transpeptidase-positive hepatic foci compared with the DENA control. PE also attenuated DENA-induced hepatic lipid peroxidation and protein oxidation. Mechanistic studies revealed that PE elevated gene expression of an array of hepatic antioxidant and carcinogen detoxifying enzymes in DENA-exposed animals. PE elevated protein and messenger RNA expression of the hepatic nuclear factor E2-related factor 2 (Nrf2). Our results provide substantial evidence, for the first time, that pomegranate constituents afford chemoprevention of hepatocarcinogenesis possibly through potent antioxidant activity achieved by upregulation of several housekeeping genes under the control of Nrf2 without toxicity. The outcome of this study strongly supports the development of pomegranate-derived products in the prevention and treatment of human HCC, which remains a devastating disease. PMID:21389260

Pharmacokinetics of Dietary Cancer Chemopreventive Compound Dibenzoylmethane in the Rats and Impacts of Nanoemulsion and Genetic knockout of Nrf2 on its Disposition

OpenAIRE

Lin, Wen; Hong, Jin-Liern; Shen, Guoxiang; Wu, Rachel T.; Wu, Yuwen; Huang, Mou-Tuan; Newmark, Harold L.; Huang, Qingrong; Khor, Tin Oo; Heimbach, Tycho; Kong, Ah-Ng

2010-01-01

The pharmacokinetic disposition of a dietary cancer chemopreventive compound dibenzoylmethane (DBM) was studied in male Sprague-Dawley rats after intravenous (i.v.) and oral (p.o.) administrations. Following a single i.v. bolus dose, the mean plasma clearance (CL) of DBM was low as compared to the hepatic blood flow. DBM displayed a high volume of distribution (Vss). The elimination terminal t1/2 was long. The mean CL, Vss and AUC0-∞/dose were similar between the i.v. 10 and 10 mg/kg doses. A...

ent-Rosane and abietane diterpenoids as cancer chemopreventive agents.

Science.gov (United States)

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

2011-04-01

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

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.

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

Science.gov (United States)

Li, Shenghong; Qiu, Shengxiang; Yao, Ping; Sun, Handong; Fong, Harry H S; Zhang, Hongjie

2013-01-01

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 9 α -hydroxy-13(14)-labden-16,15-amide (2) and 6 β -acetoxy-9 α -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.

Cancer preventive and curative attributes of plants of the Cactaceae family: a review.

Science.gov (United States)

Harlev, Eli; Nevo, Eviatar; Solowey, Elaine; Bishayee, Anupam

2013-06-01

The ever-increasing occurrence of cancer and the severe side effects and limited efficacy of current cancer chemotherapy based on chemical drugs shift the attention toward drugs of plant origin. The Cactaceae family comprises more than 1500 species, but until recently only a few of them have been tested for their chemopreventive and anticancer attributes, leaving a wide unexplored area still waiting for researchers to investigate. Considering this fact, and also the promising results obtained with the relatively few plants of this family already tested, it should justly be expected that some plants of the Cactaceae family yet unexplored might possess outstanding anticancer attributes, exceeding those displayed by the plants already tested. This review presents in vitro and in vivo experimental evidence on cancer chemopreventive and therapeutic potential of bioactive phytoconstituents and extracts derived from cactus plants. It also examines the underlying biochemical and molecular mechanisms involved in the antineoplastic effects of plants of the Cactaceae family. Current limitation and future directions of research towards effective use of cacti to develop efficient and side effect-free future cancer-preventive and anticancer drugs are also discussed. Georg Thieme Verlag KG Stuttgart · New York.

Targeting lipid metabolism of cancer cells: A promising therapeutic strategy for cancer.

Science.gov (United States)

Liu, Qiuping; Luo, Qing; Halim, Alexander; Song, Guanbin

2017-08-10

One of the most important metabolic hallmarks of cancer cells is deregulation of lipid metabolism. In addition, enhancing de novo fatty acid (FA) synthesis, increasing lipid uptake and lipolysis have also been considered as means of FA acquisition in cancer cells. FAs are involved in various aspects of tumourigenesis and tumour progression. Therefore, targeting lipid metabolism is a promising therapeutic strategy for human cancer. Recent studies have shown that reprogramming lipid metabolism plays important roles in providing energy, macromolecules for membrane synthesis, and lipid signals during cancer progression. Moreover, accumulation of lipid droplets in cancer cells acts as a pivotal adaptive response to harmful conditions. Here, we provide a brief review of the crucial roles of FA metabolism in cancer development, and place emphasis on FA origin, utilization and storage in cancer cells. Understanding the regulation of lipid metabolism in cancer cells has important implications for exploring a new therapeutic strategy for management and treatment of cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Breast Cancer Chemoprevention: A Network Meta-Analysis of Randomized Controlled Trials.

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Mocellin, Simone; Pilati, Pierluigi; Briarava, Marta; Nitti, Donato

2016-02-01

Several agents have been advocated for breast cancer primary prevention. However, few of them appear effective, the associated severe adverse effects limiting their uptake. We performed a comprehensive search for randomized controlled trials (RCTs) reporting on the ability of chemoprevention agents (CPAs) to reduce the incidence of primary breast carcinoma. Using network meta-analysis, we ranked CPAs based simultaneously on efficacy and acceptability (an inverse measure of toxicity). All statistical tests were two-sided. We found 48 eligible RCTs, enrolling 271 161 women randomly assigned to receive either placebo or one of 21 CPAs. Aromatase inhibitors (anastrozole and exemestane, considered a single CPA class because of the lack of between-study heterogeneity; relative risk [RR] = 0.468, 95% confidence interval [CI] = 0.346 to 0.634), arzoxifene (RR = 0.415, 95% CI = 0.253 to 0.682), lasofoxifene (RR = 0.208, 95% CI = 0.079 to 0.544), raloxifene (RR = 0.572, 95% CI = 0.372 to 0.881), tamoxifen (RR = 0.708, 95% CI = 0.595 to 0.842), and tibolone (RR = 0.317, 95% CI = 0.127 to 0.792) were statistically significantly associated with a therapeutic effect, which was restricted to estrogen receptor-positive tumors of postmenopausal women (except for tamoxifen, which is active also during premenopause). Network meta-analysis ranking showed that the new selective estrogen receptor modulators (SERMs) arzoxifene, lasofoxifene, and raloxifene have the best benefit-risk ratio. Aromatase inhibitors and tamoxifen ranked second and third, respectively. These results provide physicians and health care regulatory agencies with RCT-based evidence on efficacy and acceptability of currently available breast cancer CPAs; at the same time, we pinpoint how much work still remains to be done before pharmacological primary prevention becomes a routine option to reduce the burden of this disease. © The Author 2015. Published by Oxford University Press. All rights reserved. For

Kaempferol nanoparticles achieve strong and selective inhibition of ovarian cancer cell viability

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Luo, Haitao; Jiang, Bingbing; Li, Bingyun; Li, Zhaoliang; Jiang, Bing-Hua; Chen, Yi Charlie

2012-01-01

Ovarian cancer is one of the leading causes of cancer death for women throughout the Western world. Kaempferol, a natural flavonoid, has shown promise in the chemoprevention of ovarian cancer. A common concern about using dietary supplements for chemoprevention is their bioavailability. Nanoparticles have shown promise in increasing the bioavailability of some chemicals. Here we developed five different types of nanoparticles incorporating kaempferol and tested their efficacy in the inhibition of viability of cancerous and normal ovarian cells. We found that positively charged nanoparticle formulations did not lead to a significant reduction in cancer cell viability, whereas nonionic polymeric nanoparticles resulted in enhanced reduction of cancer cell viability. Among the nonionic polymeric nanoparticles, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) nanoparticles incorporating kaempferol led to significant reduction in cell viability of both cancerous and normal cells. Poly(DL-lactic acid-co-glycolic acid) (PLGA) nanoparticles incorporating kaempferol resulted in enhanced reduction of cancer cell viability together with no significant reduction in cell viability of normal cells compared with kaempferol alone. Therefore, both PEO-PPO-PEO and PLGA nanoparticle formulations were effective in reducing cancer cell viability, while PLGA nanoparticles incorporating kaempferol had selective toxicity against cancer cells and normal cells. A PLGA nanoparticle formulation could be advantageous in the prevention and treatment of ovarian cancers. On the other hand, PEO-PPO-PEO nanoparticles incorporating kaempferol were more effective inhibitors of cancer cells, but they also significantly reduced the viability of normal cells. PEO-PPO-PEO nanoparticles incorporating kaempferol may be suitable as a cancer-targeting strategy, which could limit the effects of the nanoparticles on normal cells while retaining their potency against cancer cells. We

Dietary Glucosinolates Sulforaphane, Phenethyl Isothiocyanate, Indole-3-Carbinol/3,3'-Diindolylmethane: Anti-Oxidative Stress/Inflammation, Nrf2, Epigenetics/Epigenomics and In Vivo Cancer Chemopreventive Efficacy.

Science.gov (United States)

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

2015-05-01

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

Kaiware Daikon (Raphanus sativus L.) extract: a naturally multipotent chemopreventive agent.

Science.gov (United States)

Barillari, Jessica; Iori, Renato; Papi, Alessio; Orlandi, Marina; Bartolini, Giovanna; Gabbanini, Simone; Pedulli, Gian Franco; Valgimigli, Luca

2008-09-10

Brassica vegetables are attracting major attention as healthy foods because of their content of glucosinolates (GLs) that release the corresponding isothiocyanates (ITCs) upon myrosinase hydrolysis. A number of studies have so far documented the chemopreventive properties of some ITCs. On the other hand, single nutrients detached from the food itself risk being somewhat "reductive", since plants contain several classes of compounds endowed with a polyhedral mechanism of action. Our recent finding that 4-methylthio-3-butenyl isothiocyanate (GRH-ITC) and 4-methylsulfinyl-3-butenyl isothiocyanate (GRE-ITC), released by the GLs purified from Japanese (Kaiware) Daikon (Raphanus sativus L.) seeds and sprouts, had selective cytotoxic/apoptotic activity on three human colon carcinoma cell lines prompted further research on the potential chemopreventive role of a standardized Kaiware Daikon extract (KDE), containing 10.5% w/w GRH and 3.8% w/w GRE, compared to its isolated components. KDE administered in combination with myrosinase at doses corresponding to 50 microM GRH-ITC plus 15 microM GRE-ITC (50 microM KDE-ITC) to three human cancer cell lines (LoVo, HCT-116 and HT-29) significantly reduced cell growth by 94-96% of control in six days (p oxygen consumption rate), as monitored by Clark-type microelectrode oxygen-uptake kinetics, and induced very fast quenching of DPPH. radical in methanol with t(1/2) (s) = (1.47 +/- 0.25) x 10(-2)/[KDE; (g/L)], measured by stopped-flow UV-vis kinetics at 298 K. The potential chemopreventive role of KDE is discussed.

Chemopreventive properties of curcumin analogues ...

African Journals Online (AJOL)

Chemopreventive properties of curcumin analogues, ... These compounds .... using microscope with 400 × magnification. APC ... Figure 3: Microscopic images of rat colorectal tissue stained with APC rabbit polyclonal antibody with different.

Red Wine Polyphenols for Cancer Prevention

Science.gov (United States)

He, Shan; Sun, Cuirong; Pan, Yuanjiang

2008-01-01

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. PMID:19325788

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.

Dietary Bioactive Diallyl Trisulfide in Cancer Prevention and Treatment.

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Puccinelli, Michael T; Stan, Silvia D

2017-07-28

Bioactive dietary agents have been shown to regulate multiple cancer hallmark pathways. Epidemiologic studies have linked consumption of Allium vegetables, such as garlic and onions, to decreased incidence of cancer. Diallyl trisulfide (DATS), a bioactive compound derived from Allium vegetables, has been investigated as an anti-cancer and chemopreventive agent. Preclinical studies provide ample evidence that DATS regulates multiple cancer hallmark pathways including cell cycle, apoptosis, angiogenesis, invasion, and metastasis. DATS has been shown to arrest cancer cells at multiple stages of the cell cycle with the G2/M arrest being the most widely reported. Additionally, increased pro-apoptotic capacity as a result of regulating intrinsic and extrinsic apoptotic pathway components has been widely reported following DATS treatment. Invasion, migration, and angiogenesis represent emerging targets of DATS and support its anti-cancer properties. This review summarizes DATS mechanisms of action as an anti-cancer and chemopreventive agent. These studies provide rationale for future investigation into its use as a cancer chemopreventive agent.

BMI-1, a promising therapeutic target for human cancer

Science.gov (United States)

WANG, MIN-CONG; LI, CHUN-LI; CUI, JIE; JIAO, MIN; WU, TAO; JING, LI; NAN, KE-JUN

2015-01-01

BMI-1 oncogene is a member of the polycomb-group gene family and a transcriptional repressor. Overexpression of BMI-1 has been identified in various human cancer tissues and is known to be involved in cancer cell proliferation, cell invasion, distant metastasis, chemosensitivity and patient survival. Accumulating evidence has revealed that BMI-1 is also involved in the regulation of self-renewal, differentiation and tumor initiation of cancer stem cells (CSCs). However, the molecular mechanisms underlying these biological processes remain unclear. The present review summarized the function of BMI-1 in different human cancer types and CSCs, and discussed the signaling pathways in which BMI-1 is potentially involved. In conclusion, BMI-1 may represent a promising target for the prevention and therapy of various cancer types. PMID:26622537

Beyond COX-1: the effects of aspirin on platelet biology and potential mechanisms of chemoprevention.

Science.gov (United States)

Ornelas, Argentina; Zacharias-Millward, Niki; Menter, David G; Davis, Jennifer S; Lichtenberger, Lenard; Hawke, David; Hawk, Ernest; Vilar, Eduardo; Bhattacharya, Pratip; Millward, Steven

2017-06-01

After more than a century, aspirin remains one of the most commonly used drugs in western medicine. Although mainly used for its anti-thrombotic, anti-pyretic, and analgesic properties, a multitude of clinical studies have provided convincing evidence that regular, low-dose aspirin use dramatically lowers the risk of cancer. These observations coincide with recent studies showing a functional relationship between platelets and tumors, suggesting that aspirin's chemopreventive properties may result, in part, from direct modulation of platelet biology and biochemistry. Here, we present a review of the biochemistry and pharmacology of aspirin with particular emphasis on its cyclooxygenase-dependent and cyclooxygenase-independent effects in platelets. We also correlate the results of proteomic-based studies of aspirin acetylation in eukaryotic cells with recent developments in platelet proteomics to identify non-cyclooxygenase targets of aspirin-mediated acetylation in platelets that may play a role in its chemopreventive mechanism.

Selenium Supranutrition: Are the Potential Benefits of Chemoprevention Outweighed by the Promotion of Diabetes and Insulin Resistance?

Science.gov (United States)

Rocourt, Caroline R. B.; Cheng, Wen-Hsing

2013-01-01

Selenium was considered a toxin until 1957, when this mineral was shown to be essential in the prevention of necrotic liver damage in rats. The hypothesis of selenium chemoprevention is principally formulated by the observations that cancer incidence is inversely associated with selenium status. However, recent clinical and epidemiological studies demonstrate a role for some selenoproteins in exacerbating or promoting other disease states, specifically type 2 diabetes, although other data support a role of selenium in stimulating insulin sensitivity. Therefore, it is clear that our understanding in the role of selenium in glucose metabolism and chemoprevention is inadequate and incomplete. Research exploring the role of selenium in individual healthcare is of upmost importance and possibly will help explain how selenium is a double-edged sword in the pathologies of chronic diseases. PMID:23603996

Polyethylene Glycol Mediated Colorectal Cancer Chemoprevention: Roles of Epidermal Growth Factor Receptor and Snail

Science.gov (United States)

Wali, Ramesh K.; Kunte, Dhananjay P.; Koetsier, Jennifer L.; Bissonnette, Marc; Roy, Hemant K.

2008-01-01

Polyethylene glycol (PEG) is a clinically widely used agent with profound chemopreventive properties in experimental colon carcinogenesis. We previously reported that Snail/β-catenin signaling may mediate the suppression of epithelial proliferation by PEG, although the upstream events remain unclear. We report herein the role of epidermal growth factor receptor (EGFR), a known mediator of Snail and overepressed in ~80% of human colorectal cancers (CRC), on PEG-mediated anti-proliferative and hence anti-neoplastic effects in azoxymethane (AOM)-rats and HT-29 colon cancer cells. AOM-rats were randomized to either standard diet or one with 10% PEG 3350 and euthanized 8 weeks later. The colonic samples were subjected to immunohistochemical or Western blot analyses. PEG decreased mucosal EGFR by 60% (pPEG effects were obtained in HT-29 cells. PEG suppressed EGFR protein via lysosmal degradation with no change in mRNA levels. To show that EGFR antagonism per se was responsible for the antiproliferative effect, we inhibited EGFR by either pre-treating cells with gefitinib or stably transfecting with EGFR-shRNA and measured the effect of PEG on proliferation. In either case PEG effect was blunted suggesting a vital role of EGFR. Flow cytometric analysis revealed that EGFR-shRNA cells, besides having reduced membrane EGFR also expressed low Snail levels (40%), corroborating a strong association. Furthermore, in EGFR silenced cells PEG effect on EGFR or Snail was muted, similar to that on proliferation. In conclusion, we show that EGFR is the proximate membrane signaling molecule through which PEG initiates antiproliferative activity with Snail/β-catenin pathway playing the central intermediary function. PMID:18790788

Polyethylene glycol-mediated colorectal cancer chemoprevention: roles of epidermal growth factor receptor and Snail.

Science.gov (United States)

Wali, Ramesh K; Kunte, Dhananjay P; Koetsier, Jennifer L; Bissonnette, Marc; Roy, Hemant K

2008-09-01

Polyethylene glycol (PEG) is a clinically widely used agent with profound chemopreventive properties in experimental colon carcinogenesis. We reported previously that Snail/beta-catenin signaling may mediate the suppression of epithelial proliferation by PEG, although the upstream events remain unclear. We report herein the role of epidermal growth factor receptor (EGFR), a known mediator of Snail and overexpressed in approximately 80% of human colorectal cancers, on PEG-mediated antiproliferative and hence antineoplastic effects in azoxymethane (AOM) rats and HT-29 colon cancer cells. AOM rats were randomized to either standard diet or one with 10% PEG-3350 and euthanized 8 weeks later. The colonic samples were subjected to immunohistochemical or Western blot analyses. PEG decreased mucosal EGFR by 60% (P PEG effects were obtained in HT-29 cells. PEG suppressed EGFR protein via lysosmal degradation with no change in mRNA levels. To show that EGFR antagonism per se was responsible for the antiproliferative effect, we inhibited EGFR by either pretreating cells with gefitinib or stably transfecting with EGFR-short hairpin RNA and measured the effect of PEG on proliferation. In either case, PEG effect was blunted, suggesting a vital role of EGFR. Flow cytometric analysis revealed that EGFR-short hairpin RNA cells, besides having reduced membrane EGFR, also expressed low Snail levels (40%), corroborating a strong association. Furthermore, in EGFR silenced cells, PEG effect on EGFR or Snail was muted, similar to that on proliferation. In conclusion, we show that EGFR is the proximate membrane signaling molecule through which PEG initiates antiproliferative activity with Snail/beta-catenin pathway playing the central intermediary function.

The epigenetic promise for prostate cancer diagnosis.

Science.gov (United States)

Van Neste, Leander; Herman, James G; Otto, Gaëtan; Bigley, Joseph W; Epstein, Jonathan I; Van Criekinge, Wim

2012-08-01

Prostate cancer is the most common cancer diagnosis in men and a leading cause of death. Improvements in disease management would have a significant impact and could be facilitated by the development of biomarkers, whether for diagnostic, prognostic, or predictive purposes. The blood-based prostate biomarker PSA has been part of clinical practice for over two decades, although it is surrounded by controversy. While debates of usefulness are ongoing, alternatives should be explored. Particularly with recent recommendations against routine PSA-testing, the time is ripe to explore promising biomarkers to yield a more efficient and accurate screening for detection and management of prostate cancer. Epigenetic changes, more specifically DNA methylation, are amongst the most common alterations in human cancer. These changes are associated with transcriptional silencing of genes, leading to an altered cellular biology. One gene in particular, GSTP1, has been widely studied in prostate cancer. Therefore a meta-analysis has been conducted to examine the role of this and other genes and the potential contribution to prostate cancer management and screening refinement. More than 30 independent, peer reviewed studies have reported a consistently high sensitivity and specificity of GSTP1 hypermethylation in prostatectomy or biopsy tissue. The meta-analysis combined and compared these results. GSTP1 methylation detection can serve an important role in prostate cancer managment. The meta-analysis clearly confirmed a link between tissue DNA hypermethylation of this and other genes and prostate cancer. Detection of DNA methylation in genes, including GSTP1, could serve an important role in clinical practice. Copyright © 2011 Wiley Periodicals, Inc.

MRI to assess chemoprevention in transgenic adenocarcinoma of mouse prostate (TRAMP)

International Nuclear Information System (INIS)

Arbab, Ali S; Shankar, Adarsh; Varma, Nadimpalli RS; Deeb, Dorrah; Gao, Xiaohua; Iskander, ASM; Janic, Branislava; Ali, Meser M; Gautam, Subhash C

2011-01-01

indicating higher number of tumor foci, which was also proven by histology. In vivo MRI is helpful in determining the efficacy of chemoprevention of prostate cancer in TRAMP mice

A randomized phase II chemoprevention trial of 13-CIS retinoic acid with or without alpha tocopherol or observation in subjects at high risk for lung cancer.

Science.gov (United States)

Kelly, Karen; Kittelson, John; Franklin, Wilbur A; Kennedy, Timothy C; Klein, Catherine E; Keith, Robert L; Dempsey, Edward C; Lewis, Marina; Jackson, Mary K; Hirsch, Fred R; Bunn, Paul A; Miller, York E

2009-05-01

No chemoprevention strategies have been proven effective for lung cancer. We evaluated the effect of 13-cis retinoic acid (13-cis RA), with or without alpha tocopherol, as a lung cancer chemoprevention agent in a phase II randomized controlled clinical trial of adult subjects at high risk for lung cancer as defined by the presence of sputum atypia, history of smoking, and airflow obstruction, or a prior surgically cured nonsmall cell lung cancer (disease free, >3 years). Subjects were randomly assigned to receive either 13-cis RA, 13-cis RA plus alpha tocopherol (13-cis RA/alpha toco) or observation for 12 months. Outcome measures are derived from histologic evaluation of bronchial biopsy specimens obtained by bronchoscopy at baseline and follow-up. The primary outcome measure is treatment "failure" defined as histologic progression (any increase in the maximum histologic score) or failure to return for follow-up bronchoscopy. Seventy-five subjects were randomized (27/22/26 to observations/13-cis RA/13-cis RA/alpha toco); 59 completed the trial; 55 had both baseline and follow-up bronchoscopy. The risk of treatment failure was 55.6% (15 of 27) and 50% (24 of 48) in the observation and combined (13 cis RA plus 13 cis RA/alpha toco) treatment arms, respectively (odds ratio adjusted for baseline histology, 0.97; 95% confidence interval, 0.36-2.66; P = 0.95). Among subjects with complete histology data, maximum histology score in the observation arm increased by 0.37 units and by 0.03 units in the treated arms (difference adjusted for baseline, -0.18; 95% confidence interval, -1.16 to 0.81; P = 0.72). Similar (nonsignificant) results were observed for treatment effects on endobronchial proliferation as assessed by Ki-67 immunolabeling. Twelve-month treatment with 13-cis RA produced nonsignificant changes in bronchial histology, consistent with results in other trials. Agents advancing to phase III randomized trials should produce greater histologic changes. The

A Randomized Phase II Chemoprevention Trial of 13-CIS Retinoic Acid with Or without α Tocopherol or Observation in Subjects at High Risk for Lung Cancer

Science.gov (United States)

Kelly, Karen; Kittelson, John; Franklin, Wilbur A.; Kennedy, Timothy C.; Klein, Catherine E.; Keith, Robert L.; Dempsey, Edward C.; Lewis, Marina; Jackson, Mary K.; Hirsch, Fred R.; Bunn, Paul A.; Miller, York E.

2011-01-01

No chemoprevention strategies have been proven effective for lung cancer. We evaluated the effect of 13-cis retinoic acid (13-cis RA), with or without α tocopherol, as a lung cancer chemoprevention agent in a phase II randomized controlled clinical trial of adult subjects at high risk for lung cancer as defined by the presence of sputum atypia, history of smoking, and airflow obstruction, or a prior surgically cured nonsmall cell lung cancer (disease free, >3 years). Subjects were randomly assigned to receive either 13-cis RA, 13-cis RA plus α tocopherol (13-cis RA/α toco) or observation for 12 months. Outcome measures are derived from histologic evaluation of bronchial biopsy specimens obtained by bronchoscopy at baseline and follow-up. The primary outcome measure is treatment “failure” defined as histologic progression (any increase in the maximum histologic score) or failure to return for follow-up bronchoscopy. Seventy-five subjects were randomized (27/22/26 to obervations/13-cis RA/13-cis RA/α toco); 59 completed the trial; 55 had both baseline and follow-up bronchoscopy. The risk of treatment failure was 55.6% (15 of 27) and 50% (24 of 48) in the observation and combined (13 cis RA plus 13 cis RA/α toco) treatment arms, respectively (odds ratio adjusted for baseline histology, 0.97; 95% confidence interval, 0.36–2.66; P = 0.95). Among subjects with complete histology data, maximum histology score in the observation arm increased by 0.37 units and by 0.03 units in the treated arms (difference adjusted for baseline, −0.18; 95% confidence interval, −1.16 to 0.81; P = 0.72). Similar (nonsignificant) results were observed for treatment effects on endobronchial proliferation as assessed by Ki-67 immunolabeling. Twelve-month treatment with 13-cis RA produced nonsignificant changes in bronchial histology, consistent with results in other trials. Agents advancing to phase III randomized trials should produce greater histologic changes. The addition of �

Targeting arachidonic acid pathway by natural products for cancer prevention and therapy.

Science.gov (United States)

Yarla, Nagendra Sastry; Bishayee, Anupam; Sethi, Gautam; Reddanna, Pallu; Kalle, Arunasree M; Dhananjaya, Bhadrapura Lakkappa; Dowluru, Kaladhar S V G K; Chintala, Ramakrishna; Duddukuri, Govinda Rao

2016-10-01

Arachidonic acid (AA) pathway, a metabolic process, plays a key role in carcinogenesis. Hence, AA pathway metabolic enzymes phospholipase A 2 s (PLA 2 s), cyclooxygenases (COXs) and lipoxygenases (LOXs) and their metabolic products, such as prostaglandins and leukotrienes, have been considered novel preventive and therapeutic targets in cancer. Bioactive natural products are a good source for development of novel cancer preventive and therapeutic drugs, which have been widely used in clinical practice due to their safety profiles. AA pathway inhibitory natural products have been developed as chemopreventive and therapeutic agents against several cancers. Curcumin, resveratrol, apigenin, anthocyans, berberine, ellagic acid, eugenol, fisetin, ursolic acid, [6]-gingerol, guggulsteone, lycopene and genistein are well known cancer chemopreventive agents which act by targeting multiple pathways, including COX-2. Nordihydroguaiaretic acid and baicalein can be chemopreventive molecules against various cancers by inhibiting LOXs. Several PLA 2 s inhibitory natural products have been identified with chemopreventive and therapeutic potentials against various cancers. In this review, we critically discuss the possible utility of natural products as preventive and therapeutic agents against various oncologic diseases, including prostate, pancreatic, lung, skin, gastric, oral, blood, head and neck, colorectal, liver, cervical and breast cancers, by targeting AA pathway. Further, the current status of clinical studies evaluating AA pathway inhibitory natural products in cancer is reviewed. In addition, various emerging issues, including bioavailability, toxicity and explorability of combination therapy, for the development of AA pathway inhibitory natural products as chemopreventive and therapeutic agents against human malignancy are also discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemopreventive effects of NSAIDs as inhibitors of cyclooxygenase-2 and inducers of apoptosis in experimental lung carcinogenesis.

Science.gov (United States)

Setia, Shruti; Vaish, Vivek; Sanyal, Sankar Nath

2012-07-01

Roles of cyclooxygenase (COX) enzyme and intrinsic pathway of apoptosis have been explored for the chemopreventive effects of non-steroidal anti-inflammatory drugs (NSAIDs) on 9,10-dimethyl benz(a)anthracene (DMBA)-induced lung cancer in rat model. 16 weeks after the administration of DMBA, morphological analysis revealed the occurrences of tumours and lesions, which were regressed considerably with the co-administration of indomethacin and etoricoxib, the two NSAIDs under investigation. DMBA group was marked by hyperplasia and dysplasia as observed by histological examination, and these features were corrected to a large extent by the two NSAIDs. Elevated levels of COX-2 were seen in the DMBA group, the enzyme responsible for prostaglandin synthesis during inflammation and cancer, whilst the expression of the constitutive isoform, COX-1, was equally expressed in all the groups. Apoptosis was quantified by studying the activities of apaf-1, caspase-9, and 3 by immunofluorescence and western blots. Their activities were found to diminish in the DMBA-treated animals as compared to the other groups. Fluorescent co-staining of the isolated broncho-alveolar lavage cells showed reduced number of apoptotic cells in the DMBA group, indicating decrease in apoptosis after carcinogen administration. The present results thus suggest that the mechanism of cancer chemoprevention of NSAIDs may include the suppression of COX-2 and the induction of apoptosis.

NSAIDs and Cell Proliferation in Colorectal Cancer

Directory of Open Access Journals (Sweden)

Raj Ettarh

2010-06-01

Full Text Available Colon cancer is common worldwide and accounts for significant morbidity and mortality in patients. Fortunately, epidemiological studies have demonstrated that continuous therapy with NSAIDs offers real promise of chemoprevention and adjunct therapy for colon cancer patients. Tumour growth is the result of complex regulation that determines the balance between cell proliferation and cell death. How NSAIDs affect this balance is important for understanding and improving treatment strategies and drug effectiveness. NSAIDs inhibit proliferation and impair the growth of colon cancer cell lines when tested in culture in vitro and many NSAIDs also prevent tumorigenesis and reduce tumour growth in animal models and in patients, but the relationship to inhibition of tumour cell proliferation is less convincing, principally due to gaps in the available data. High concentrations of NSAIDs are required in vitro to achieve cancer cell inhibition and growth retardation at varying time-points following treatment. However, the results from studies with colon cancer cell xenografts are promising and, together with better comparative data on anti-proliferative NSAID concentrations and doses (for in vitro and in vivo administration, could provide more information to improve our understanding of the relationships between these agents, dose and dosing regimen, and cellular environment.

Burden and Chemoprevention of Skin Cancer

NARCIS (Netherlands)

L.M. Hollestein (Loes)

2013-01-01

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

Nutrients, foods, and colorectal cancer prevention.

Science.gov (United States)

Song, Mingyang; Garrett, Wendy S; Chan, Andrew T

2015-05-01

Diet has an important role in the development of colorectal cancer. In the past few decades, findings from extensive epidemiologic and experimental investigations have linked consumption of several foods and nutrients to the risk of colorectal neoplasia. Calcium, fiber, milk, and whole grains have been associated with a lower risk of colorectal cancer, and red meat and processed meat have been associated with an increased risk. There is substantial evidence for the potential chemopreventive effects of vitamin D, folate, fruits, and vegetables. Nutrients and foods also may interact, as a dietary pattern, to influence colorectal cancer risk. Diet likely influences colorectal carcinogenesis through several interacting mechanisms. These include the direct effects on immune responsiveness and inflammation, and the indirect effects of overnutrition and obesity-risk factors for colorectal cancer. Emerging evidence also implicates the gut microbiota as an important effector in the relationship between diet and cancer. Dietary modification therefore has the promise of reducing colorectal cancer incidence. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Transforming Cancer Prevention through Precision Medicine and Immune-oncology.

Science.gov (United States)

Kensler, Thomas W; Spira, Avrum; Garber, Judy E; Szabo, Eva; Lee, J Jack; Dong, Zigang; Dannenberg, Andrew J; Hait, William N; Blackburn, Elizabeth; Davidson, Nancy E; Foti, Margaret; Lippman, Scott M

2016-01-01

We have entered a transformative period in cancer prevention (including early detection). Remarkable progress in precision medicine and immune-oncology, driven by extraordinary recent advances in genome-wide sequencing, big-data analytics, blood-based technologies, and deep understanding of the tumor immune microenvironment (TME), has provided unprecedented possibilities to study the biology of premalignancy. The pace of research and discovery in precision medicine and immunoprevention has been astonishing and includes the following clinical firsts reported in 2015: driver mutations detected in circulating cell-free DNA in patients with premalignant lesions (lung); clonal hematopoiesis shown to be a premalignant state; molecular selection in chemoprevention randomized controlled trial (RCT; oral); striking efficacy in RCT of combination chemoprevention targeting signaling pathway alterations mechanistically linked to germline mutation (duodenum); molecular markers for early detection validated for lung cancer and showing promise for pancreatic, liver, and ovarian cancer. Identification of HPV as the essential cause of a major global cancer burden, including HPV16 as the single driver of an epidemic of oropharyngeal cancer in men, provides unique opportunities for the dissemination and implementation of public health interventions. Important to immunoprevention beyond viral vaccines, genetic drivers of premalignant progression were associated with increasing immunosuppressive TME; and Kras vaccine efficacy in pancreas genetically engineered mouse (GEM) model required an inhibitory adjuvant (Treg depletion). In addition to developing new (e.g., epigenetic) TME regulators, recent mechanistic studies of repurposed drugs (aspirin, metformin, and tamoxifen) have identified potent immune activity. Just as precision medicine and immune-oncology are revolutionizing cancer therapy, these approaches are transforming cancer prevention. Here, we set out a brief agenda for the

The Prevention of Hereditary Breast and Ovarian Cancer: A Personal View

Directory of Open Access Journals (Sweden)

Narod Steven

2004-02-01

Full Text Available Abstract Options for the prevention of hereditary breast and ovarian cancer include screening, preventive surgery and chemoprevention. Screening studies with magnetic resonance imaging of the breast are promising but the technology is not widespread and MRI is unlikely to be available as a screening tool in the near future. Prophylactic oophorectomy and mastectomy are effective preventive measures and are gaining in acceptance by patients and physicians. Preventive mastectomy is effective against both primary and contralateral breast cancer. Oophorectomy prevents ovarian cancer, and if done prior to menopause, will prevent breast cancer as well. Tamoxifen has been shown to prevent contralateral breast cancers in BRCA1 and BRCA2 carriers but is not widely accepted as a means of primary prevention. Oral contraceptives and tubal ligation will reduce the risk of hereditary ovarian cancer and should be considered in women who wish to retain ovarian function.

Promising oncolytic agents for metastatic breast cancer treatment

Directory of Open Access Journals (Sweden)

Cody JJ

2015-06-01

Full Text Available James J Cody,1 Douglas R Hurst2 1ImQuest BioSciences, Frederick, MD, 2Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA Abstract: New therapies for metastatic breast cancer patients are urgently needed. The long-term survival rates remain unacceptably low for patients with recurrent disease or disseminated metastases. In addition, existing therapies often cause a variety of debilitating side effects that severely impact quality of life. Oncolytic viruses constitute a developing therapeutic modality in which interest continues to build due to their ability to spare normal tissue while selectively destroying tumor cells. A number of different viruses have been used to develop oncolytic agents for breast cancer, including herpes simplex virus, adenovirus, vaccinia virus, measles virus, reovirus, and others. In general, clinical trials for several cancers have demonstrated excellent safety records and evidence of efficacy. However, the impressive tumor responses often observed in preclinical studies have yet to be realized in the clinic. In order for the promise of oncolytic virotherapy to be fully realized for breast cancer patients, effectiveness must be demonstrated in metastatic disease. This review provides a summary of oncolytic virotherapy strategies being developed to target metastatic breast cancer. Keywords: oncolytic virus, virotherapy, breast cancer, metastasis 

Gene therapy a promising treatment for breast cancer: current scenario in pakistan

International Nuclear Information System (INIS)

Muzavir, S.R.; Zahra, S.A.; Ahmad, A.

2012-01-01

Breast cancer is one of the most common cancers among women around the world. It accounts for 22.9% of all the cancers and 18% of all female cancers in the world. One million new cases of breast cancer are diagnosed every year. Pakistan has more alarming situation with 90,000 new cases and ending up into 40,000 deaths annually. The risk factor for a female to develop breast cancer as compared with male is 100 : 1. The traditional way of treatment is by surgery, chemotherapy or radiotherapy. Advanced breast cancer is very difficult to treat with any of the traditional treatment options. A new treatment option in the form of gene therapy can be a promising treatment for breast cancer. Gene therapy provides treatment option in the form of targeting mutated gene, expression of cancer markers on the surface of cells, blocking the metastasis and induction of apoptosis, etc. Gene therapy showed very promising results for treatment of various cancers. All this is being trialed, experimented and practiced outside of Pakistan. Therefore, there is an immense need that this kind of work should be started in Pakistan. There are many good research institutes as well as well-reputed hospitals in Pakistan. Presently, there is a need to develop collaboration between research institutes and hospitals, so that the basic work and clinical trials can be done to treat breast cancer patients in the country. This collaboration will prove to be very healthy and will not only strength research institute but also will be very beneficial for cancer patients. (author)

Chemopreventive effect of Cynodon dactylon (L.) Pers. extract against DMH-induced colon carcinogenesis in experimental animals.

Science.gov (United States)

Albert-Baskar, Arul; Ignacimuthu, Savarimuthu

2010-07-01

The present study was aimed at evaluating the chemopreventive property of Cynodon dactylon. The antioxidant, antiproliferative and apoptotic potentials of the plant were investigated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, nitric oxide radical scavenging activity (NO(-)) and MTT assay on four cancer cell lines (COLO 320 DM, MCH-7, AGS, A549) and a normal cell line (VERO). In vivo chemopreventive property of the plant extract was studied in DMH-induced colon carcinogenesis. The methanolic extract of C. dactylon was found to be antiproliferative and antioxidative at lower concentrations and induced apoptotic cell death in COLO 320 DM cells. Treatment with methanolic extract of C. dactylon increased the levels of antioxidant enzymes and reduced the number of dysplastic crypts in DMH-induced colon of albino rats. The present investigation revealed the anticancer potential of methanolic extract of C. dactylon in COLO 320 DM cells and experimentally induced colon carcinogenesis in rats.

Development of New Treatments for Prostate Cancer

Energy Technology Data Exchange (ETDEWEB)

DiPaola, R. S.; Abate-Shen, C.; Hait, W. N.

2005-02-01

chemoprevention are underway. The specific goals of this program are: (1) To investigate the molecular mechanisms underlying normal prostate growth and differentiation and elucidate the molecular mechanisms underlying prostate oncogenesis. (2) To build on fundamental knowledge to develop effective therapeutic approaches for the treatment of prostate cancer. (3) To improve the control of prostate cancer through early detection, chemoprevention, and outreach and education. This new disease-based program is structured to improve interdisciplinary interactions and translational results. Already, through the dynamic leadership of Drs. Cory Abate-Shen and Robert DiPaola, new investigators were attracted to the field, new collaborations engendered, and numerous investigator-initiated trials implemented. Progress in GPCC and the program overall has been outstanding. The Center has success in uniting investigators with broad and complementary expertise in prostate cancer research. The overall goal and unifying theme is to elucidate basic mechanisms of prostate growth and oncogenesis, with the ultimate goal of promoting new and effective strategies for the eradication of prostate cancer in patients and populations at risk. Members wide range of research interests collectively optimize the chances of providing new insights into normal prostate biology and unraveling the molecular pathophysiology of prostate cancer. Studies in cell culture and powerful animal models developed recapitulate the various stages of prostate cancer progression, including prostatic intraepithelial neoplasia, adenocarcinoma, androgen-independence, invasion and metastases. These models promise to further strengthen an already robust program of investigator-initiated therapeutic clinical trials, including studies adopted by national cooperative groups. Efforts to translate laboratory results into clinical studies of early detection and chemoprevention are underway.

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

Directory of Open Access Journals (Sweden)

Carina Michl

Full Text Available 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.

Nrf2: bane or blessing in cancer?

Science.gov (United States)

Xiang, MingJun; Namani, Akhileshwar; Wu, ShiJun; Wang, XiaoLi

2014-08-01

The Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor-E2-related factor 2 (Nrf2)-antioxidant response element pathway serves a major function in endogenous cytoprotection in normal cells. Nrf2 is a transcription factor that mainly regulates the expression of a wide array of genes that produce the antioxidants and other proteins responsible for the detoxification of xenobiotics and reactive oxygen species. Nrf2 mediates the chemoprevention of cancer in normal cells. Growing body of evidence suggests that Nrf2 is not only involved in the chemoprevention of normal cells but also promotes the growth of cancer cells. However, the mechanism underlying the function of Nrf2 in oncogenesis and tumor protection in cancer cells remains unclear and thus requires further study. This review aims to rationalize the existing functions of Nrf2 in chemoprevention and tumorigenesis, as well as the somatic mutations of Nrf2 and Keap1 in cancer and Nrf2 cross talk with miRNAs. This review also discusses the future challenges in Nrf2 research.

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

Inhibition of Akt enhances the chemopreventive effects of topical rapamycin in mouse skin

Science.gov (United States)

Dickinson, Sally E; Janda, Jaroslav; Criswell, Jane; Blohm-Mangone, Karen; Olson, Erik R.; Liu, Zhonglin; Barber, Christie; Rusche, Jadrian J.; Petricoin, Emmanuel; Calvert, Valerie; Einspahr, Janine G.; Dickinson, Jesse; Stratton, Steven P.; Curiel-Lewandrowski, Clara; Saboda, Kathylynn; Hu, Chengcheng; Bode, Ann M.; Dong, Zigang; Alberts, David S.; Bowden, G. Timothy

2016-01-01

The PI3Kinase/Akt/mTOR pathway has important roles in cancer development for multiple tumor types, including UV-induced non-melanoma skin cancer. Immunosuppressed populations are at increased risk of aggressive cutaneous squamous cell carcinoma (SCC). Individuals who are treated with rapamycin, (sirolimus, a classical mTOR inhibitor) have significantly decreased rates of developing new cutaneous SCCs compared to those that receive traditional immunosuppression. However, systemic rapamycin use can lead to significant adverse events. Here we explored the use of topical rapamycin as a chemopreventive agent in the context of solar simulated light (SSL)-induced skin carcinogenesis. In SKH-1 mice, topical rapamycin treatment decreased tumor yields when applied after completion of 15 weeks of SSL exposure compared to controls. However, applying rapamycin during SSL exposure for 15 weeks, and continuing for 10 weeks after UV treatment, increased tumor yields. We also examined whether a combinatorial approach might result in more significant tumor suppression by rapamycin. We validated that rapamycin causes increased Akt (S473) phosphorylation in the epidermis after SSL, and show for the first time that this dysregulation can be inhibited in vivo by a selective PDK1/Akt inhibitor, PHT-427. Combining rapamycin with PHT-427 on tumor prone skin additively caused a significant reduction of tumor multiplicity compared to vehicle controls. Our findings indicate that patients taking rapamycin should avoid sun exposure, and that combining topical mTOR inhibitors and Akt inhibitors may be a viable chemoprevention option for individuals at high risk for cutaneous SCC.

Occult progression by Apc-deficient intestinal crypts as a target for chemoprevention

Science.gov (United States)

Liskay, R.Michael

2014-01-01

Although Apc mutation is widely considered an initiating event in colorectal cancer, little is known about the earliest stages of tumorigenesis following sporadic Apc loss. Therefore, we have utilized a novel mouse model that facilitates the sporadic inactivation of Apc via frameshift reversion of Cre in single, isolated cells and subsequently tracks the fates of Apc-deficient intestinal cells. Our results suggest that consistent with Apc being a ‘gatekeeper’, loss of Apc early in life during intestinal growth leads to adenomas or increased crypt fission, manifested by fields of mutant but otherwise normal-appearing crypts. In contrast, Apc loss occurring later in life has minimal consequences, with mutant crypts being less prone to either increased crypt fission or adenoma formation. Using the stem cell-specific Lgr5-CreER mouse, we generated different sized fields of Apc-deficient crypts via independent recombination events and found that field size correlates with progression to adenoma. To evaluate this early stage prior to adenoma formation as a therapeutic target, we examined the chemopreventive effects of sulindac on Apc-deficient occult crypt fission. We found that sulindac treatment started early in life inhibits the morphologically occult spread of Apc-deficient crypts and thus reduces adenoma numbers. Taken together these results suggest that: (i) earlier Apc loss promotes increased crypt fission, (ii) a field of Apc-deficient crypts, which can form via occult crypt fission or independent neighboring events, is an important intermediate between loss of Apc and adenoma formation and (iii) normal-appearing Apc-deficient crypts are potential unappreciated targets for cancer screening and chemoprevention. PMID:23996931

Selenium and Breast Cancer Chemoprevention

National Research Council Canada - National Science Library

Thompson, Henry J

2005-01-01

.... The intermediate biomarkers being studied are as follows: indicators of oxidative damage to cellular macromolecules such as DNA and lipids, indicators of IGF metabolic status, and cellular indicators of breast cancer risk...

Breast cancer prevention strategies in lobular carcinoma in situ: A decision analysis.

Science.gov (United States)

Wong, Stephanie M; Stout, Natasha K; Punglia, Rinaa S; Prakash, Ipshita; Sagara, Yasuaki; Golshan, Mehra

2017-07-15

Women diagnosed with lobular carcinoma in situ (LCIS) have a 3-fold to 10-fold increased risk of developing invasive breast cancer. The objective of this study was to evaluate the life expectancy (LE) and differences in survival offered by active surveillance, risk-reducing chemoprevention, and bilateral prophylactic mastectomy among women with LCIS. A Markov simulation model was constructed to determine average LE and quality-adjusted LE (QALE) gains for hypothetical cohorts of women diagnosed with LCIS at various ages under alternative risk-reduction strategies. Probabilities for invasive breast cancer, breast cancer-specific mortality, other-cause mortality and the effectiveness of preventive strategies were derived from published studies and from the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Assuming a breast cancer incidence from 1.02% to 1.37% per year under active surveillance, a woman aged 50 years diagnosed with LCIS would have a total LE of 32.78 years and would gain 0.13 years (1.6 months) in LE by adding chemoprevention and 0.25 years (3.0 months) in LE by adding bilateral prophylactic mastectomy. After quality adjustment, chemoprevention resulted in the greatest QALE for women ages 40 to 60 years at LCIS diagnosis, whereas surveillance remained the preferred strategy for optimizing QALE among women diagnosed at age 65 years and older. In this model, among women with a diagnosis of LCIS, breast cancer prevention strategies only modestly affected overall survival, whereas chemoprevention was modeled as the preferred management strategy for optimizing invasive disease-free survival while prolonging QALE form women younger than 65 years. Cancer 2017;123:2609-17. © 2017 American Cancer Society. © 2017 American Cancer Society.

Long Term Exposure to Polyphenols of Artichoke (Cynara scolymus L.) Exerts Induction of Senescence Driven Growth Arrest in the MDA-MB231 Human Breast Cancer Cell Line.

Science.gov (United States)

Mileo, Anna Maria; Di Venere, Donato; Abbruzzese, Claudia; Miccadei, Stefania

2015-01-01

Polyphenolic extracts from the edible part of artichoke (Cynara scolymus L.) have been shown to be potential chemopreventive and anticancer dietary compounds. High doses of polyphenolic extracts (AEs) induce apoptosis and decrease the invasive potential of the human breast cancer cell line, MDA-MB231. However, the molecular mechanism underlying AEs antiproliferative effects is not completely understood. We demonstrate that chronic and low doses of AEs treatment at sublethal concentrations suppress human breast cancer cell growth via a caspases-independent mechanism. Furthermore, AEs exposure induces a significant increase of senescence-associated β-galactosidase (SA-β-gal) staining and upregulation of tumour suppressor genes, p16(INK4a) and p21(Cip1/Waf1) in MDA-MB231 cells. AEs treatment leads to epigenetic alterations in cancer cells, modulating DNA hypomethylation and lysine acetylation levels in total proteins. Cell growth arrest correlates with increased reactive oxygen species (ROS) production in AEs treated breast cancer cells. Inhibition of ROS generation by N-acetylcysteine (NAC) attenuates the antiproliferative effect. These findings demonstrate that chronic AEs treatment inhibits breast cancer cell growth via the induction of premature senescence through epigenetic and ROS-mediated mechanisms. Our results suggest that artichoke polyphenols could be a promising dietary tool either in cancer chemoprevention or/and in cancer treatment as a nonconventional, adjuvant therapy.

Novel inhibitor of DNA ligase IV with a promising cancer therapeutic ...

Indian Academy of Sciences (India)

Home; Journals; Journal of Biosciences; Volume 39; Issue 3. Novel inhibitor of DNA ligase IV with a promising cancer therapeutic potential. Ashwin Kotnis Rita Mulherkar. Clipboards Volume 39 Issue 3 June 2014 pp 339-340. Fulltext. Click here to view fulltext PDF. Permanent link:

Arctigenin in combination with quercetin synergistically enhances the antiproliferative effect in prostate cancer cells.

Science.gov (United States)

Wang, Piwen; Phan, Tien; Gordon, David; Chung, Seyung; Henning, Susanne M; Vadgama, Jaydutt V

2015-02-01

We investigated whether a combination of two promising chemopreventive agents arctigenin (Arc) and quercetin (Q) increases the anticarcinogenic potency at lower concentrations than necessary when used individually in prostate cancer. Androgen-dependent LAPC-4 and LNCaP prostate cancer cells were treated with low doses of Arc and Q alone or in combination for 48 h. The antiproliferative activity of Arc was 10- to 20-fold stronger than Q in both cell lines. Their combination synergistically enhanced the antiproliferative effect, with a stronger effect in androgen receptor (AR) wild-type LAPC-4 cells than in AR mutated LNCaP cells. Arc demonstrated a strong ability to inhibit AR protein expression in LAPC-4 cells. The combination treatment significantly inhibited both AR and PI3K/Akt pathways compared to control. A protein array analysis revealed that the mixture targets multiple pathways particularly in LAPC-4 cells including Stat3 pathway. The mixture significantly inhibited the expression of several oncogenic microRNAs including miR-21, miR-19b, and miR-148a compared to control. The mixture also enhanced the inhibition of cell migration in both cell lines compared to individual compounds tested. The combination of Arc and Q that target similar pathways, at low physiological doses, provides a novel regimen with enhanced chemoprevention in prostate cancer. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Newly Emerging Immune Checkpoints: Promises for Future Cancer Therapy

Directory of Open Access Journals (Sweden)

Robert J. Torphy

2017-12-01

Full Text Available Cancer immunotherapy has been a great breakthrough, with immune checkpoint inhibitors leading the way. Despite the clinical effectiveness of certain immune checkpoint inhibitors, the overall response rate remains low, and the effectiveness of immunotherapies for many tumors has been disappointing. There is substantial interest in looking for additional immune checkpoint molecules that may act as therapeutic targets for cancer. Recent advances during the last decade have identified several novel immune checkpoint targets, including lymphocyte activation gene-3 (LAG-3, B and T lymphocyte attenuator (BTLA, programmed death-1 homolog (PD-1H, T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIM-3/carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1, and the poliovirus receptor (PVR-like receptors. The investigations into these molecules have generated promising results in preclinical studies. Herein, we will summarize our current progress and understanding of these newly-characterized immune checkpoints and their potential application in cancer immunotherapy.

MIP-Based Sensors: Promising New Tools for Cancer Biomarker Determination

Directory of Open Access Journals (Sweden)

Giulia Selvolini

2017-03-01

Full Text Available Detecting cancer disease at an early stage is one of the most important issues for increasing the survival rate of patients. Cancer biomarker detection helps to provide a diagnosis before the disease becomes incurable in later stages. Biomarkers can also be used to evaluate the progression of therapies and surgery treatments. In recent years, molecularly imprinted polymer (MIP based sensors have been intensely investigated as promising analytical devices in several fields, including clinical analysis, offering desired portability, fast response, specificity, and low cost. The aim of this review is to provide readers with an overview on recent important achievements in MIP-based sensors coupled to various transducers (e.g., electrochemical, optical, and piezoelectric for the determination of cancer biomarkers by selected publications from 2012 to 2016.

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

Science.gov (United States)

Smolarek, Amanda K; Suh, Nanjoo

2011-11-01

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

Arctigenin in combination with quercetin synergistically enhances the anti-proliferative effect in prostate cancer cells

Science.gov (United States)

Wang, Piwen; Phan, Tien; Gordon, David; Chung, Seyung; Henning, Susanne M.; Vadgama, Jaydutt V.

2014-01-01

Scope We investigated whether a combination of two promising chemopreventive agents arctigenin and quercetin increases the anti-carcinogenic potency at lower concentrations than necessary when used individually in prostate cancer. Methods and results Androgen-dependent LAPC-4 and LNCaP prostate cancer cells were treated with low doses of arctigenin and quercetin alone or in combination for 48h. The anti-proliferative activity of arctigenin was 10-20 fold stronger than quercetin in both cell lines. Their combination synergistically enhanced the anti-proliferative effect, with a stronger effect in androgen receptor (AR) wild-type LAPC-4 cells than in AR mutated LNCaP cells. Arctigenin demonstrated a strong ability to inhibit AR protein expression in LAPC-4 cells. The combination treatment significantly inhibited both AR and PI3K/Akt pathways compared to control. A protein array analysis revealed that the mixture targets multiple pathways particularly in LAPC-4 cells including Stat3 pathway. The mixture significantly inhibited the expression of several oncogenic microRNAs including miR-21, miR-19b, and miR-148a compared to control. The mixture also enhanced the inhibition of cell migration in both cell lines compared to individual compounds tested. Conclusion The combination of arctigenin and quercetin, that target similar pathways, at low physiological doses, provides a novel regimen with enhanced chemoprevention in prostate cancer. PMID:25380086

Identification, synthesis, and biological evaluation of the metabolites of 3-amino-6-(3'-aminopropyl)-5H-indeno[1,2-c]isoquinoline-5,11-(6H)dione (AM6-36), a promising rexinoid lead compound for the development of cancer chemotherapeutic and chemopreventive agents.

Science.gov (United States)

Chen, Lian; Conda-Sheridan, Martin; Reddy, P V Narasimha; Morrell, Andrew; Park, Eun-Jung; Kondratyuk, Tamara P; Pezzuto, John M; van Breemen, Richard B; Cushman, Mark

2012-06-28

Activation of the retinoid X receptor (RXR), which is involved in cell proliferation, differentiation, and apoptosis, is a strategy for cancer chemotherapy and chemoprevention, and 3-amino-6-(3'-aminopropyl)-5H-indeno[1,2-c]isoquinoline-5,11-(6H)dione (AM6-36) (3) is among the few RXR ligands known. The presently reported studies of 3 include its binding to human plasma proteins, metabolic stability using human liver microsomes, metabolism by human liver microsomes and hepatocytes, and in vivo disposition in rat serum, liver, and mammary tissue. Compound 3 was 75% bound to human plasma proteins, and its metabolic stability was much greater than propranolol. One phase I metabolite was formed by human liver microsomes, seven phase I and II metabolites were formed by human hepatocytes, and five metabolites were detected in rat serum and liver after oral administration. The putative metabolites predicted using LC-MS-MS were synthesized to confirm their structures and to provide sufficient material for investigation of induction of RXRE transcriptional activity and inhibition of NFκB.

Chemopreventive Activities of Sulforaphane and Its Metabolites in Human Hepatoma HepG2 Cells

Directory of Open Access Journals (Sweden)

Peng Liu

2018-05-01

Full Text Available Sulforaphane (SFN exhibits chemopreventive effects through various mechanisms. However, few studies have focused on the bioactivities of its metabolites. Here, three metabolites derived from SFN were studied, known as sulforaphane glutathione, sulforaphane cysteine and sulforaphane-N-acetylcysteine. Their effects on cell viability, DNA damage, tumorigenicity, cell migration and adhesion were measured in human hepatoma HepG2 cells, and their anti-angiogenetic effects were determined in a 3D co-culture model of human umbilical vein endothelial cells (HUVECs and pericytes. Results indicated that these metabolites at high doses decreased cancer cell viability, induced DNA damage and inhibited motility, and impaired endothelial cell migration and tube formation. Additionally, pre-treatment with low doses of SFN metabolites protected against H2O2 challenge. The activation of the nuclear factor E2-related factor 2 (Nrf2-antioxidant response element (ARE pathway and the induction of intracellular glutathione (GSH played an important role in the cytoprotective effects of SFN metabolites. In conclusion, SFN metabolites exhibited similar cytotoxic and cytoprotective effects to SFN, which proves the necessity to study the mechanisms of action of not only SFN but also of its metabolites. Based on the different tissue distribution profiles of these metabolites, the most relevant chemical forms can be selected for targeted chemoprevention.

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

Polyphenols as Promising Drugs against Main Breast Cancer Signatures

Directory of Open Access Journals (Sweden)

María Losada-Echeberría

2017-11-01

Full Text Available Breast cancer is one of the most common neoplasms worldwide, and in spite of clinical and pharmacological advances, it is still a clinical problem, causing morbidity and mortality. On the one hand, breast cancer shares with other neoplasms some molecular signatures such as an imbalanced redox state, cell cycle alterations, increased proliferation and an inflammatory status. On the other hand, breast cancer shows differential molecular subtypes that determine its prognosis and treatment. These are characterized mainly by hormone receptors especially estrogen receptors (ERs and epidermal growth factor receptor 2 (HER2. Tumors with none of these receptors are classified as triple negative breast cancer (TNBC and are associated with a worse prognosis. The success of treatments partially depends on their specificity and the adequate molecular classification of tumors. New advances in anticancer drug discovery using natural compounds have been made in the last few decades, and polyphenols have emerged as promising molecules. They may act on various molecular targets because of their promiscuous behavior, presenting several physiological effects, some of which confer antitumor activity. This review analyzes the accumulated evidence of the antitumor effects of plant polyphenols on breast cancer, with special attention to their activity on ERs and HER2 targets and also covering different aspects such as redox balance, uncontrolled proliferation and chronic inflammation.

Polyphenols as Promising Drugs against Main Breast Cancer Signatures

Science.gov (United States)

Herranz-López, María; Micol, Vicente

2017-01-01

Breast cancer is one of the most common neoplasms worldwide, and in spite of clinical and pharmacological advances, it is still a clinical problem, causing morbidity and mortality. On the one hand, breast cancer shares with other neoplasms some molecular signatures such as an imbalanced redox state, cell cycle alterations, increased proliferation and an inflammatory status. On the other hand, breast cancer shows differential molecular subtypes that determine its prognosis and treatment. These are characterized mainly by hormone receptors especially estrogen receptors (ERs) and epidermal growth factor receptor 2 (HER2). Tumors with none of these receptors are classified as triple negative breast cancer (TNBC) and are associated with a worse prognosis. The success of treatments partially depends on their specificity and the adequate molecular classification of tumors. New advances in anticancer drug discovery using natural compounds have been made in the last few decades, and polyphenols have emerged as promising molecules. They may act on various molecular targets because of their promiscuous behavior, presenting several physiological effects, some of which confer antitumor activity. This review analyzes the accumulated evidence of the antitumor effects of plant polyphenols on breast cancer, with special attention to their activity on ERs and HER2 targets and also covering different aspects such as redox balance, uncontrolled proliferation and chronic inflammation. PMID:29112149

Selenium and Lung Cancer: A Systematic Review and Meta Analysis

Science.gov (United States)

Fritz, Heidi; Kennedy, Deborah; Fergusson, Dean; Fernandes, Rochelle; Cooley, Kieran; Seely, Andrew; Sagar, Stephen; Wong, Raimond; Seely, Dugald

2011-01-01

Background Selenium is a natural health product widely used in the treatment and prevention of lung cancers, but large chemoprevention trials have yielded conflicting results. We conducted a systematic review of selenium for lung cancers, and assessed potential interactions with conventional therapies. Methods and Findings Two independent reviewers searched six databases from inception to March 2009 for evidence pertaining to the safety and efficacy of selenium for lung cancers. Pubmed and EMBASE were searched to October 2009 for evidence on interactions with chemo- or radiation-therapy. In the efficacy analysis there were nine reports of five RCTs and two biomarker-based studies, 29 reports of 26 observational studies, and 41 preclinical studies. Fifteen human studies, one case report, and 36 preclinical studies were included in the interactions analysis. Based on available evidence, there appears to be a different chemopreventive effect dependent on baseline selenium status, such that selenium supplementation may reduce risk of lung cancers in populations with lower baseline selenium status (serumselenium (≥121.6 ng/mL). Pooling data from two trials yielded no impact to odds of lung cancer, OR 0.93 (95% confidence interval 0.61–1.43); other cancers that were the primary endpoints of these trials, OR 1.51 (95%CI 0.70–3.24); and all-cause-death, OR 0.93 (95%CI 0.79–1.10). In the treatment of lung cancers, selenium may reduce cisplatin-induced nephrotoxicity and side effects associated with radiation therapy. Conclusions Selenium may be effective for lung cancer prevention among individuals with lower selenium status, but at present should not be used as a general strategy for lung cancer prevention. Although promising, more evidence on the ability of selenium to reduce cisplatin and radiation therapy toxicity is required to ensure that therapeutic efficacy is maintained before any broad clinical recommendations can be made in this context. PMID:22073154

Chemopreventive effects of in vitro digested and fermented bread in human colon cells.

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Schlörmann, Wiebke; Hiller, Beate; Jahns, Franziska; Zöger, Romy; Hennemeier, Isabell; Wilhelm, Anne; Lindhauer, Meinolf G; Glei, Michael

2012-10-01

Bread as a staple food product represents an important source for dietary fibre consumption. Effects of wheat bread, wholemeal wheat bread and wholemeal rye bread on mechanisms which could have impact on chemoprevention were analysed in colon cells after in vitro fermentation. Effects of fermented bread samples on gene expression, glutathione S-transferase activity and glutathione content, differentiation, growth and apoptosis were investigated using the human colon adenoma cell line LT97. Additionally, apoptosis was studied in normal and tumour colon tissue by determination of caspase activities. The expression of 76 genes (biotransformation, differentiation, apoptosis) was significantly upregulated (1.5-fold) in LT97 cells. The fermented bread samples were able to significantly increase glutathione S-transferase activity (1.8-fold) and glutathione content (1.4-fold) of the cells. Alkaline phosphatase activity as a marker of differentiation was also significantly enhanced (1.7-fold). The fermented bread samples significantly inhibited LT97 cell growth and increased the level of apoptotic cells (1.8-fold). Only marginal effects on apoptosis in tumour compared to normal tissue were observed. This is the first study which presents chemopreventive effects of different breads after in vitro fermentation. In spite of differences in composition, the results were comparable between the bread types. Nevertheless, they indicate a potential involvement of this staple food product regarding the prevention of colon cancer.

Preferences for breast cancer risk reduction among BRCA1/BRCA2 mutation carriers: a discrete-choice experiment.

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Liede, Alexander; Mansfield, Carol A; Metcalfe, Kelly A; Price, Melanie A; Snyder, Carrie; Lynch, Henry T; Friedman, Sue; Amelio, Justyna; Posner, Joshua; Narod, Steven A; Lindeman, Geoffrey J; Evans, D Gareth

2017-09-01

Unaffected women who carry BRCA1 or BRCA2 mutations face difficult choices about reducing their breast cancer risk. Understanding their treatment preferences could help us improve patient counseling and inform drug trials. The objective was to explore preferences for various risk-reducing options among women with germline BRCA1/2 mutations using a discrete-choice experiment survey and to compare expressed preferences with actual behaviors. A discrete-choice experiment survey was designed wherein women choose between hypothetical treatments to reduce breast cancer risk. The hypothetical treatments were characterized by the extent of breast cancer risk reduction, treatment duration, impact on fertility, hormone levels, risk of uterine cancer, and ease and mode of administration. Data were analyzed using a random-parameters logit model. Women were also asked to express their preference between surgical and chemoprevention options and to report on their actual risk-reduction actions. Women aged 25-55 years with germline BRCA1/2 mutations who were unaffected with breast or ovarian cancer were recruited through research registries at five clinics and a patient advocacy group. Between January 2015 and March 2016, 622 women completed the survey. Breast cancer risk reduction was the most important consideration expressed, followed by maintaining fertility. Among the subset of women who wished to have children in future, the ability to maintain fertility was the most important factor, followed by the extent of risk reduction. Many more women said they would take a chemoprevention drug than had actually taken chemoprevention. Women with BRCA1/2 mutations indicated strong preferences for breast cancer risk reduction and maintaining fertility. The expressed desire to have a safe chemoprevention drug available to them was not met by current chemoprevention options.

Hydrogen sulfide-releasing naproxen suppresses colon cancer cell growth and inhibits NF-κB signaling

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Kodela R

2015-08-01

Full Text Available Ravinder Kodela,1 Niharika Nath,2 Mitali Chattopadhyay,1 Diandra E Nesbitt,1 Carlos A Velázquez-Martínez,3 Khosrow Kashfi11Department of Physiology, Pharmacology and Neuroscience, Sophie Davis School of Biomedical Education, City University of New York Medical School, 2Department of Life Sciences, New York Institute of Technology, New York, NY, USA; 3Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada Abstract: Colorectal cancer (CRC is the second leading cause of death due to cancer and the third most common cancer in men and women in the USA. Nuclear factor kappa B (NF-κB is known to be activated in CRC and is strongly implicated in its development and progression. Therefore, activated NF-κB constitutes a bona fide target for drug development in this type of malignancy. Many epidemiological and interventional studies have established nonsteroidal anti-inflammatory drugs (NSAIDs as a viable chemopreventive strategy against CRC. Our previous studies have shown that several novel hydrogen sulfide-releasing NSAIDs are promising anticancer agents and are safer derivatives of NSAIDs. In this study, we examined the growth inhibitory effect of a novel H2S-releasing naproxen (HS-NAP, which has a repertoire as a cardiovascular-safe NSAID, for its effects on cell proliferation, cell cycle phase transitions, and apoptosis using HT-29 human colon cancer cells. We also investigated its effect as a chemopreventive agent in a xenograft mouse model. HS-NAP suppressed the growth of HT-29 cells by induction of G0/G1 arrest and apoptosis and downregulated NF-κB. Tumor xenografts in mice were significantly reduced in volume. The decrease in tumor mass was associated with a reduction of cell proliferation, induction of apoptosis, and decreases in NF-κB levels in vivo. Therefore, HS-NAP demonstrates strong anticancer potential in CRC. Keywords: nonsteroidal anti-inflammatory drugs, cell cycle, apoptosis, xenograft, NF

Piper betel leaf: a reservoir of potential xenohormetic nutraceuticals with cancer-fighting properties.

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Gundala, Sushma R; Aneja, Ritu

2014-05-01

Plants contain a much greater diversity of bioactive compounds than any man-made chemical library. Heart-shaped Piper betel leaves are magnificent reservoirs of phenolic compounds with antiproliferative, antimutagenic, antibacterial, and antioxidant properties. Widely consumed in South Asian countries, the glossy leaf contains a multitude of biophenolics such as hydroxychavicol, eugenol, chavibetol, and piperols. Convincing data underscore the remarkable chemotherapeutic and chemopreventive potential of betel leaves against a variety of cancer types. The leaf constituents modulate an extensive array of signaling molecules such as transcription factors as well as reactive oxygen species (ROS) to control multiple nodes of various cellular proliferation and death pathways. Herein, we provide an overall perspective on the cancer-fighting benefits of the phenolic phytochemicals in betel leaves and a comprehensive overview of the mechanisms responsive to dose-driven ROS-mediated signaling cascades conscripted by bioactive phenolics to confer chemotherapeutic and chemopreventive advantages. Intriguingly, these ROS-triggered responses are contextual and may either elicit a protective xenohormetic antioxidant response to premalignant cells to constitute a chemopreventive effect or generate a curative chemotherapeutic response by pro-oxidatively augmenting the constitutively elevated ROS levels in cancer cells to tip the balance in favor of selective apoptosis induction in cancer cells while sparing normal ones. In conclusion, this review provides an update on how distinct ROS levels exist in normal versus cancer cells and how these levels can be strategically modulated and exploited for therapeutic gains. We emphasize the yet untapped potential of the evergreen vine, betel leaf, for chemopreventive and chemotherapeutic management of cancer.

Pomegranate for Prevention and Treatment of Cancer: An Update

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Pooja Sharma

2017-01-01

Full Text Available Cancer is the second leading cause of death in the United States, and those who survive cancer may experience lasting difficulties, including treatment side effects, as well as physical, cognitive, and psychosocial struggles. Naturally-occurring agents from dietary fruits and vegetables have received considerable attention for the prevention and treatment of cancers. These natural agents are safe and cost efficient in contrast to expensive chemotherapeutic agents, which may induce significant side effects. The pomegranate (Punica granatum L. fruit has been used for the prevention and treatment of a multitude of diseases and ailments for centuries in ancient cultures. Pomegranate exhibits strong antioxidant activity and is a rich source of anthocyanins, ellagitannins, and hydrolysable tannins. Studies have shown that the pomegranate fruit as well as its juice, extract, and oil exert anti-inflammatory, anti-proliferative, and anti-tumorigenic properties by modulating multiple signaling pathways, which suggest its use as a promising chemopreventive/chemotherapeutic agent. This review summarizes preclinical and clinical studies highlighting the role of pomegranate in prevention and treatment of skin, breast, prostate, lung, and colon cancers.

Pomegranate for Prevention and Treatment of Cancer: An Update.

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Sharma, Pooja; McClees, Sarah F; Afaq, Farrukh

2017-01-24

Cancer is the second leading cause of death in the United States, and those who survive cancer may experience lasting difficulties, including treatment side effects, as well as physical, cognitive, and psychosocial struggles. Naturally-occurring agents from dietary fruits and vegetables have received considerable attention for the prevention and treatment of cancers. These natural agents are safe and cost efficient in contrast to expensive chemotherapeutic agents, which may induce significant side effects. The pomegranate ( Punica granatum L.) fruit has been used for the prevention and treatment of a multitude of diseases and ailments for centuries in ancient cultures. Pomegranate exhibits strong antioxidant activity and is a rich source of anthocyanins, ellagitannins, and hydrolysable tannins. Studies have shown that the pomegranate fruit as well as its juice, extract, and oil exert anti-inflammatory, anti-proliferative, and anti-tumorigenic properties by modulating multiple signaling pathways, which suggest its use as a promising chemopreventive/chemotherapeutic agent. This review summarizes preclinical and clinical studies highlighting the role of pomegranate in prevention and treatment of skin, breast, prostate, lung, and colon cancers.

Chemoprevention of colon carcinogenesis by polyethylene glycol: suppression of epithelial proliferation via modulation of SNAIL/beta-catenin signaling.

Science.gov (United States)

Roy, Hemant K; Kunte, Dhananjay P; Koetsier, Jennifer L; Hart, John; Kim, Young L; Liu, Yang; Bissonnette, Marc; Goldberg, Michael; Backman, Vadim; Wali, Ramesh K

2006-08-01

Polyethylene glycol (PEG) is one of the most potent chemopreventive agents against colorectal cancer; however, the mechanisms remain largely unexplored. In this study, we assessed the ability of PEG to target cyclin D1-beta-catenin-mediated hyperproliferation in the azoxymethane-treated rat model and the human colorectal cancer cell line, HT-29. Azoxymethane-treated rats were randomized to AIN-76A diet alone or supplemented with 5% PEG-8000. After 30 weeks, animals were euthanized and biopsies of aberrant crypt foci and uninvolved crypts were subjected to immunohistochemical and immunoblot analyses. PEG markedly suppressed both early and late markers of azoxymethane-induced colon carcinogenesis (fractal dimension by 80%, aberrant crypt foci by 64%, and tumors by 74%). In both azoxymethane-treated rats and HT-29 cells treated with 5% PEG-3350 for 24 hours, PEG decreased proliferation (45% and 52%, respectively) and cyclin D1 (78% and 56%, respectively). Because beta-catenin is the major regulator of cyclin D1 in colorectal cancer, we used the T-cell factor (Tcf)-TOPFLASH reporter assay to show that PEG markedly inhibited beta-catenin transcriptional activity. PEG did not alter total beta-catenin expression but rather its nuclear localization, leading us to assess E-cadherin expression (a major determinant of beta-catenin subcellular localization), which was increased by 73% and 71% in the azoxymethane-rat and HT-29 cells, respectively. We therefore investigated the effect of PEG treatment on levels of the negative regulator of E-cadherin, SNAIL, and observed a 50% and 75% decrease, respectively. In conclusion, we show, for the first time, a molecular mechanism through which PEG imparts its antiproliferative and hence profound chemopreventive effect.

Centrosome – a promising anti-cancer target

Directory of Open Access Journals (Sweden)

Rivera-Rivera Y

2016-12-01

Full Text Available Yainyrette Rivera-Rivera, Harold I Saavedra Department of Pharmacology, Ponce Health Sciences University-School of Medicine, Ponce Research Institute, Ponce, Puerto Rico Abstract: The centrosome, an organelle discovered >100 years ago, is the main microtubule-organizing center in mammalian organisms. The centrosome is composed of a pair of centrioles surrounded by the pericentriolar material (PMC and plays a major role in the regulation of cell cycle transitions (G1-S, G2-M, and metaphase-anaphase, ensuring the normality of cell division. Hundreds of proteins found in the centrosome exert a variety of roles, including microtubule dynamics, nucleation, and kinetochore–microtubule attachments that allow correct chromosome alignment and segregation. Errors in these processes lead to structural (shape, size, number, position, and composition, functional (abnormal microtubule nucleation and disorganized spindles, and numerical (centrosome amplification [CA] centrosome aberrations causing aneuploidy and genomic instability. Compelling data demonstrate that centrosomes are implicated in cancer, because there are important oncogenic and tumor suppressor proteins that are localized in this organelle and drive centrosome aberrations. Centrosome defects have been found in pre-neoplasias and tumors from breast, ovaries, prostate, head and neck, lung, liver, and bladder among many others. Several drugs/compounds against centrosomal proteins have shown promising results. Other drugs have higher toxicity with modest or no benefits, and there are more recently developed agents being tested in clinical trials. All of this emerging evidence suggests that targeting centrosome aberrations may be a future avenue for therapeutic intervention in cancer research. Keywords: centrosomes, cell cycle, mitosis, CA, CIN, cancer therapy

CRISPR-Cas9: a promising genetic engineering approach in cancer research

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Ratan, Zubair Ahmed; Son, Young-Jin; Uddin, Bhuiyan Mohammad Mahtab; Yusuf, Md. Abdullah; Zaman, Sojib Bin; Kim, Jong-Hoon; Banu, Laila Anjuman

2018-01-01

Bacteria and archaea possess adaptive immunity against foreign genetic materials through clustered regularly interspaced short palindromic repeat (CRISPR) systems. The discovery of this intriguing bacterial system heralded a revolutionary change in the field of medical science. The CRISPR and CRISPR-associated protein 9 (Cas9) based molecular mechanism has been applied to genome editing. This CRISPR-Cas9 technique is now able to mediate precise genetic corrections or disruptions in in vitro and in vivo environments. The accuracy and versatility of CRISPR-Cas have been capitalized upon in biological and medical research and bring new hope to cancer research. Cancer involves complex alterations and multiple mutations, translocations and chromosomal losses and gains. The ability to identify and correct such mutations is an important goal in cancer treatment. In the context of this complex cancer genomic landscape, there is a need for a simple and flexible genetic tool that can easily identify functional cancer driver genes within a comparatively short time. The CRISPR-Cas system shows promising potential for modeling, repairing and correcting genetic events in different types of cancer. This article reviews the concept of CRISPR-Cas, its application and related advantages in oncology. PMID:29434679

Andrographolide and analogues in cancer prevention.

Science.gov (United States)

Mishra, Siddhartha Kumar; Tripathi, Swati; Shukla, Archana; Oh, Seung Hyun; Kim, Hwan Mook

2015-01-01

Andrographis paniculata is a medicinal plant traditionally used for treatment of cough and cold, fever, laryngitis, and several infectious diseases. Extracts of A. paniculata have shown versatile potency against various diseases including cancer. The active biomolecules of A. paniculata mainly are lactone and diterpene. Andrographolide and analogues have been widely used for prevention of different diseases. Andrographolides have shown potent antiinflammatory and anticancer activities. It showed potentials as chemopreventive agents by suppressing growth of cancer cells by inhibiting NF-kappaB, PI3K/AKT and other kinase pathways and by inducing apoptosis. Andrographolide induced both intrinsic and extrinsic apoptosis pathway in different cancer cells via expression of different anti-apoptotic protein like Bax, p53, and activated caspases. Andrographolide was successfully used as an antineoplastic drug in cancer chemotherapy. Andrographolide inhibited the growth of human breast, prostate, and hepatoma tumors. Andrographolide and analogues need to be subjected to further clinical and biomedical studies in cancer chemoprevention. Andrographolide could be potent anticancer agent when used in combination with other chemotherapeutic agents.

Aspirin in the Chemoprevention of Colorectal Neoplasia: An Overview

Science.gov (United States)

Chan, Andrew T.; Arber, Nadir; Burn, John; Chia, John Whay-Kuang; Elwood, Peter; Hull, Mark A.; Logan, Richard F.; Rothwell, Peter M.; Schrör, Karsten; Baron, John A.

2011-01-01

Considerable evidence supports the effectiveness of aspirin for chemoprevention of colorectal cancer (CRC) in addition to its well-established benefits in the prevention of vascular disease. Epidemiologic studies have consistently observed an inverse association between aspirin use and risk of CRC. A recent pooled analysis of a long-term post-trial follow-up of nearly 14,000 patients from 4 randomized, cardiovascular disease prevention trials showed that daily aspirin treatment for about 5 years was associated with a 34% reduction in 20-year CRC mortality. A separate meta-analysis of nearly 3,000 patients with a history of colorectal adenoma or cancer in 4 randomized adenoma prevention trials demonstrated that aspirin reduced the occurrence of advanced adenomas by 28% and any adenoma by 17%. Aspirin has also been shown to be beneficial in a clinical trial of patients with Lynch syndrome, a hereditary CRC syndrome; in those treated with aspirin for at least 2 years, there was a ≥ 50% reduction in the risk of CRC commencing 5 years after randomization and after aspirin had been discontinued. A few observational studies have shown an increase in survival among patients with CRC who use aspirin. Taken together, these findings strengthen the case for consideration of long-term aspirin use in CRC prevention. Despite these compelling data, there is a lack of consensus about the balance of risks and benefits associated with long-term aspirin use, particularly in low-risk populations. The optimal dose to use for cancer prevention and the precise mechanism underlying aspirin’s anticancer effect require further investigation. PMID:22084361

Sulindac treatment in hereditary non-pollyposis colorectal cancer

NARCIS (Netherlands)

Rijcken, Fleur E. M.; Hollema, Harry; van der Zee, Ate G. J.; van der Sluis, Tineke; Ek, Wytske Boersma-van; Kleibeuker, Jan H.

Non-steroidal anti-inflammatory drugs, e.g. sulindac have been extensively studied for chemoprevention in familial adenomatous polyposis, but not in hereditary non-polyposis colorectal cancer (HNPCC). We evaluated these effects in HNPCC using surrogate end-points for cancer risk. In a randomised

Convergence of nanotechnology and cancer prevention: are we there yet?

Science.gov (United States)

Menter, David G; Patterson, Sherri L; Logsdon, Craig D; Kopetz, Scott; Sood, Anil K; Hawk, Ernest T

2014-10-01

Nanotechnology is emerging as a promising modality for cancer treatment; however, in the realm of cancer prevention, its full utility has yet to be determined. Here, we discuss the potential of integrating nanotechnology in cancer prevention to augment early diagnosis, precision targeting, and controlled release of chemopreventive agents, reduced toxicity, risk/response assessment, and personalized point-of-care monitoring. Cancer is a multistep, progressive disease; the functional and acquired characteristics of the early precancer phenotype are intrinsically different from those of a more advanced anaplastic or invasive malignancy. Therefore, applying nanotechnology to precancers is likely to be far more challenging than applying it to established disease. Frank cancers are more readily identifiable through imaging and biomarker and histopathologic assessment than their precancerous precursors. In addition, prevention subjects routinely have more rigorous intervention criteria than therapy subjects. Any nanopreventive agent developed to prevent sporadic cancers found in the general population must exhibit a very low risk of serious side effects. In contrast, a greater risk of side effects might be more acceptable in subjects at high risk for cancer. Using nanotechnology to prevent cancer is an aspirational goal, but clearly identifying the intermediate objectives and potential barriers is an essential first step in this exciting journey. ©2014 American Association for Cancer Research.

Programmed death-1 & its ligands: promising targets for cancer immunotherapy.

Science.gov (United States)

Shrimali, Rajeev K; Janik, John E; Abu-Eid, Rasha; Mkrtichyan, Mikayel; Khleif, Samir N

2015-01-01

Novel strategies for cancer treatment involving blockade of immune inhibitors have shown significant progress toward understanding the molecular mechanism of tumor immune evasion. The preclinical findings and clinical responses associated with programmed death-1 (PD-1) and PD-ligand pathway blockade seem promising, making these targets highly sought for cancer immunotherapy. In fact, the anti-PD-1 antibodies, pembrolizumab and nivolumab, were recently approved by the US FDA for the treatment of unresectable and metastatic melanoma resistant to anticytotoxic T-lymphocyte antigen-4 antibody (ipilimumab) and BRAF inhibitor. Here, we discuss strategies of combining PD-1/PD-ligand interaction inhibitors with other immune checkpoint modulators and standard-of-care therapy to break immune tolerance and induce a potent antitumor activity, which is currently a research area of key scientific pursuit.

Transcription Factor STAT3 as a Novel Molecular Target for Cancer Prevention

International Nuclear Information System (INIS)

Xiong, Ailian; Yang, Zhengduo; Shen, Yicheng; Zhou, Jia; Shen, Qiang

2014-01-01

Signal Transducers and Activators of Transcription (STATs) are a family of transcription factors that regulate cell proliferation, differentiation, apoptosis, immune and inflammatory responses, and angiogenesis. Cumulative evidence has established that STAT3 has a critical role in the development of multiple cancer types. Because it is constitutively activated during disease progression and metastasis in a variety of cancers, STAT3 has promise as a drug target for cancer therapeutics. Recently, STAT3 was found to have an important role in maintaining cancer stem cells in vitro and in mouse tumor models, suggesting STAT3 is integrally involved in tumor initiation, progression and maintenance. STAT3 has been traditionally considered as nontargetable or undruggable, and the lag in developing effective STAT3 inhibitors contributes to the current lack of FDA-approved STAT3 inhibitors. Recent advances in cancer biology and drug discovery efforts have shed light on targeting STAT3 globally and/or specifically for cancer therapy. In this review, we summarize current literature and discuss the potential importance of STAT3 as a novel target for cancer prevention and of STAT3 inhibitors as effective chemopreventive agents

Quantification of 4'-geranyloxyferulic acid, a new natural colon cancer chemopreventive agent, by HPLC-DAD in grapefruit skin extract.

Science.gov (United States)

Genovese, S; Epifano, F; Carlucci, G; Marcotullio, M C; Curini, M; Locatelli, M

2010-10-10

Oxyprenylated natural products (isopentenyloxy-, geranyloxy- and the less spread farnesyloxy-compounds and their biosynthetic derivatives) represent a family of secondary metabolites that have been consider for years merely as biosynthetic intermediates of the most abundant C-prenylated derivatives. Many of the isolated oxyprenylated natural products were shown to exert in vitro and in vivo remarkable anti-cancer and anti-inflammatory effects. 4'-Geranyloxyferulic acid [3-(4'-geranyloxy-3'-methoxyphenyl)-2-trans-propenoic] has been discovered as a valuable chemopreventive agent of several types of cancer. After development of a high yield and "eco-friendly" synthetic scheme of this secondary metabolite, starting from cheap and non-toxic reagents and substrates, we developed a new HPLC-DAD method for its quantification in grapefruit skin extract. A preliminary study on C18 column showed the separation between GOFA and boropinic acid (having the same core but with an isopentenyloxy side chain), used as internal standard. The tested column were thermostated at 28+/-1 degrees C and the separation was achieved in gradient condition at a flow rate of 1 mL/min with a starting mobile phase of H(2)O:methanol (40:60, v/v, 1% formic acid). The limit of detection (LOD, S/N=3) was 0.5 microg/mL and the limit of quantification (LOQ, S/N=10) was 1 microg/mL. Matrix-matched standard curves showed linearity up to 75 microg/mL. In the analytical range the precision (RSD%) values were extract of grapefruit. In conclusion, this method showed LOQ values able to selective quantification of this analyte in grapefruit skin extract.

[Latest international guidelines for screening, prevention and treatment of familial breast cancer - implications for the relevant practice in Hungary].

Science.gov (United States)

Romics, László; Kocsis, Judit; Ormándi, Katalin; Molnár, Béla Ákos

2016-07-01

Screening, prevention and treatment of familial breast cancer require a multidisciplinary approach. New guidelines were published in the United Kingdom for the management of familial breast cancer. The authors summarise these new guidelines and analyse the relevant practice in Hungary. Relevant guidelines of the National Institute for Health and Care Excellence and Familial Breast Cancer Report (NHS Scotland) are described. New guidelines will increase the number of genetic tests as well as genetic counselling. An increase in the number of breast magnetic resonance imaging is expected, too. Chemoprevention can be offered for individuals with medium risk and above. Promising trials are underway with platinum based chemotherapy and polyADP-ribose polimerase inhibitors for the systemic treatment of familial breast cancer. The increase in the number of genetic tests, counselling, and breast magnetic resonance imaging may have a significant impact on health care budget. These guidelines will change some aspects of the current management of familial breast cancer. Orv. Hetil., 2016, 157(28), 1117-1125.

Exploring the molecular targets of dietary flavonoid fisetin in cancer.

Science.gov (United States)

Syed, Deeba N; Adhami, Vaqar Mustafa; Khan, Naghma; Khan, Mohammad Imran; Mukhtar, Hasan

2016-10-01

The last few decades have seen a resurgence of interest among the scientific community in exploring the efficacy of natural compounds against various human cancers. Compounds of plant origin belonging to different groups such as alkaloids, flavonoids and polyphenols evaluated for their cancer preventive effects have yielded promising data, thereby offering a potential therapeutic alternative against this deadly disease. The flavonol fisetin (3,3',4',7-tetrahydroxyflavone), present in fruits and vegetables such as strawberries, apple, cucumber, persimmon, grape and onion, was shown to possess anti-microbial, anti-inflammatory, anti-oxidant and more significantly anti-carcinogenic activity when assessed in diverse cell culture and animal model systems. The purpose of this review is to update and discuss key findings obtained till date from in vitro and in vivo studies on fisetin, with special focus on its anti-cancer role. The molecular mechanism(s) described in the observed growth inhibitory effects of fisetin in different cancer cell types is also summarized. Moreover, an attempt is made to delineate the direction of future studies that could lead to the development of fisetin as a potent chemopreventive/chemotherapeutic agent against cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

Phytochemicals attenuating aberrant activation of β-catenin in cancer cells.

Directory of Open Access Journals (Sweden)

Dan Wang

Full Text Available Phytochemicals are a rich source of chemoprevention agents but their effects on modulating the Wnt/β-catenin signaling pathway have remained largely uninvestigated. Aberrantly activated Wnt signaling can result in the abnormal stabilization of β-catenin, a key causative step in a broad spectrum of cancers. Here we report the modulation of lithium chloride-activated canonical Wnt/β-catenin signaling by phytochemicals that have antioxidant, anti-inflammatory or chemopreventive properties. The compounds were first screened with a cervical cancer-derived stable Wnt signaling reporter HeLa cell line. Positive hits were subsequently evaluated for β-catenin degradation, suppression of β-catenin nuclear localization and down-regulation of downstream oncogenic targets of Wnt/β-catenin pathway. Our study shows a novel degradation path of β-catenin protein in HeLa cells by Avenanthramide 2p (a polyphenol and Triptolide (a diterpene triepoxide, respectively from oats and a Chinese medicinal plant. The findings present Avenanthramide 2p as a potential chemopreventive dietary compound that merits further study using in vivo models of cancers; they also provide a new perspective on the mechanism of action of Triptolide.

Evaluation of chemopreventive and cytotoxic effect of lemon seed extracts on human breast cancer (MCF-7) cells.

Science.gov (United States)

Kim, Jinhee; Jayaprakasha, Guddadarangavvanahally K; Uckoo, Ram M; Patil, Bhimanagouda S

2012-02-01

Extracts from lemon seed were investigated for the radical scavenging activity and apoptotic effects in human breast adenocarcinoma (MCF-7) cells and non-malignant breast (MCF-12F) cells for the first time. Defatted seed powder was successively extracted with ethyl acetate (EtOAc), acetone, methanol (MeOH), and MeOH:water (80:20). The chemical constituents were identified and quantified by LC-MS and HPLC analysis, respectively. The highest radical scavenging activity of 62.2% and 91.3% was exhibited by MeOH:water (80:20) at 833μg/mL in 1,1-diphenyl-2-picryl hydrazyl (DPPH) and 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS(+)), respectively. In addition, the MeOH:water (80:20) extract showed the highest (29.1%, Pwater (80:20) extract induced DNA fragmentation and poly(ADP-ribose) polymerase (PARP) cleavage. Increased levels of Bax and cytosolic cytochrome C and decreased levels of Bcl2 were also observed in MeOH:water (80:20) treated MCF-7 cells. In conclusion, the MeOH:water (80:20) extract from lemon seed has potent antioxidant activity and induces apoptosis in MCF-7 cells, leading to the inhibition of proliferation. These results suggest that aglycones and glucosides of the limonoids and flavonoid present in MeOH:water (80:20) extract may potentially serve as a chemopreventive agent for breast cancer. Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemoprevention Trial of Selenium and Prostate Cancer

Science.gov (United States)

1999-10-01

use in slowing the growth of prostate cancer. This study will not use selenium as a treatment option for the possible cure of prostate cancer...slice or 1 piece o Q rj Chocolate candy and candy bars o o o o o Q o o c 1 small bar or 1 ounce ._> . ■Q Hard candy, jam, jelly, honey , or...your stream? Have you noticed any stress incontinence? (leakage of urine when sneezing, coughing or laughing) _1 -NOT AT ALL _ 2-LESS THAN 1 IN 5

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)

Qin Jie; Xie Liping; Zheng Xiangyi; Wang Yunbin; Bai Yu; Shen Huafeng; Li Longcheng; Dahiya, Rajvir

2007-01-01

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

Breast Cancer Prevention (PDQ®)—Health Professional Version

Science.gov (United States)

Risk factors for breast cancer are female sex and advancing age, inherited risk, breast density, obesity, alcohol consumption, and exposure to ionizing radiation. Interventions to prevent breast cancer include chemoprevention (e.g. SERMs, AIs), risk-reducing surgery (e.g. mastectomy, oophorectomy). Review the evidence on risk factors and interventions to prevent breast cancer in this expert-reviewed summary.

Low Prostate Concentration of Lycopene Is Associated with Development of Prostate Cancer in Patients with High-Grade Prostatic Intraepithelial Neoplasia

Science.gov (United States)

Mariani, Simone; Lionetto, Luana; Cavallari, Michele; Tubaro, Andrea; Rasio, Debora; De Nunzio, Cosimo; Hong, Gena M.; Borro, Marina; Simmaco, Maurizio

2014-01-01

Prostate cancer (PC) is a frequent male malignancy and represents the second most diagnosed cancer in men. Since pre-cancerous lesions, i.e., the high-grade prostatic intraepithelial neoplasia (HGPIN), can be detected years before progression to PC, early diagnosis and chemoprevention are targeted strategies to reduce PC rates. Animal studies have shown that lycopene, a carotenoid contained in tomatoes, is a promising candidate for the chemoprevention of PC. However, its efficacy in humans remains controversial. The present study aimed to investigate the relevance of plasma and prostate concentration of lycopene after a lycopene-enriched diet in patients diagnosed with HGPIN. Thirty-two patients diagnosed with HGPIN were administered a lycopene-enriched diet (20–25 mg/day of lycopene; through 30 g/day of triple concentrated tomato paste) for 6 months. A 6-month follow-up prostate biopsy assessed progression to PC. Patients were classified into three groups according to the histopathological features of the 6-month follow-up biopsy results: prostatitis; HGPIN and PC. PSA and plasma lycopene levels were measured before and after the dietary lycopene supplementation. Prostatic lycopene concentration was only assessed after the supplementation diet. Only prostatic lycopene concentration showed significant differences between the three groups (p = 0.03). Prostatic lycopene concentration below a 1 ng/mg threshold was associated with PC at 6-month follow-up biopsy (p = 0.003). We observed no overall benefits from a 6-month lycopene supplementation, as the rate of HGPIN progression to PC in our population (9/32, 28%) was similar to rates reported in the literature. Baseline PSA levels also showed no significant changes after a lycopene-enriched diet. Our findings point to prostatic lycopene concentration as a promising biomarker of PC. Further prospective longitudinal studies are needed to assess the prognostic role of prostatic lycopene in PC. PMID:24451130

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.

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)

Heidor, Renato; Furtado, Kelly Silva; Ortega, Juliana Festa; Oliveira, Tiago Franco de; Tavares, Paulo Eduardo Latorre Martins; Vieira, Alessandra; Miranda, Mayara Lilian Paulino; Purgatto, Eduardo; Moreno, Fernando Salvador

2014-01-01

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

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...

The role of Clinical Geneticists in Hereditary Cancer Management and Research

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Hanne Meijers Heijboer

2017-02-01

Full Text Available Abstract Hereditary cancer refers to cancers caused by germline mutations in cancer predisposing genes. These mutations confer a significantly increased risk of cancer, are rare, and are in the majority of cases autosomal dominantly inherited.  Since the eighties of last century more than 115 cancer predisposing genes have been identified. In many Western countries genetic testing of patients and families with clustering of cancers started early, and was often performed by clinical geneticists (MDs performed the counselling and pedigree analyses and by molecular biologists (in laboratories within departments of clinical genetics.  It turned out to be a long path to fully realize the promise of cancer predisposing genes. The clinical utility of many cancer genetic tests and subsequent risk reducing interventions has not yet been validated and pitfalls in e.g. misinterpretation of genetic variants showed up. However, without doubt genetic testing for mutations will eventually turn out as a strong tool to save lives from early cancer death and will become part of standard cancer care throughout the developed world.  Apart from primary surgical prevention, major progress is to be expected in earlier diagnoses, tailored therapies, and possibly chemoprevention.  Ideally researchers, clinical geneticists, molecular biologists, surgeons, oncologists, gynaecologists and other professionals will work together to reach this goal. Keywords : clinical genetics, germline, hereditary cancers, cancer predisposing genes

The diagnosis and management of pre-invasive breast disease: Promise of new technologies in understanding pre-invasive breast lesions

International Nuclear Information System (INIS)

Jeffrey, Stefanie S; Pollack, Jonathan R

2003-01-01

Array-based comparative genomic hybridization, RNA expression profiling, and proteomic analyses are new molecular technologies used to study breast cancer. Invasive breast cancers were originally evaluated because they provided ample quantities of DNA, RNA, and protein. The application of these technologies to pre-invasive breast lesions is discussed, including methods that facilitate their implementation. Data indicate that atypical ductal hyperplasia and ductal carcinoma in situ are precursor lesions molecularly similar to adjacent invasive breast cancer. It is expected that molecular technologies will identify breast tissue at risk for the development of unfavorable subtypes of invasive breast cancer and reveal strategies for targeted chemoprevention or eradication

Protective molecular mechanisms of resveratrol in UVR-induced Skin carcinogenesis.

Science.gov (United States)

Aziz, Saba W; Aziz, Moammir H

2018-01-01

Skin cancer is a major health problem worldwide. It is the most common cancer in the United States and poses a significant healthcare burden. Excessive UVR exposure is the most common cause of skin cancer. Despite various precautionary measures to avoid direct UVR exposure, the incidence of skin cancer and mortality related to it remains high. Furthermore, the current treatment options are expensive and have side effects including toxicity to normal cells. Thus, a safe and effective approach is needed to prevent and treat skin cancer. Chemopreventive strategy using naturally occurring compounds, such as resveratrol, is a promising approach to reduce the incidence of UVR-induced skin cancer and delay its progression. This review highlights the current body of evidence related to chemopreventive role of resveratrol and its molecular mechanisms in UVR-induced skin carcinogenesis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Notch activation is dispensable for D, L-sulforaphane-mediated inhibition of human prostate cancer cell migration.

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Eun-Ryeong Hahm

Full Text Available D, L-Sulforaphane (SFN, a synthetic racemic analog of broccoli constituent L-sulforaphane, is a highly promising cancer chemopreventive agent with in vivo efficacy against chemically-induced as well as oncogene-driven cancer in preclinical rodent models. Cancer chemopreventive effect of SFN is characterized by G(2/M phase cell cycle arrest, apoptosis induction, and inhibition of cell migration and invasion. Moreover, SFN inhibits multiple oncogenic signaling pathways often hyperactive in human cancers, including nuclear factor-κB, Akt, signal transducer and activator of transcription 3, and androgen receptor. The present study was designed to determine the role of Notch signaling, which is constitutively active in many human cancers, in anticancer effects of SFN using prostate cancer cells as a model. Exposure of human prostate cancer cells (PC-3, LNCaP, and/or LNCaP-C4-2B to SFN as well as its naturally-occurring thio-, sulfinyl-, and sulfonyl-analogs resulted in cleavage (activation of Notch1, Notch2, and Notch4, which was accompanied by a decrease in levels of full-length Notch forms especially at the 16- and 24-hour time points. The SFN-mediated cleavage of Notch isoforms was associated with its transcriptional activation as evidenced by RBP-Jk-, HES-1A/B- and HEY-1 luciferase reporter assays. Migration of PC-3 and LNCaP cells was decreased significantly by RNA interference of Notch1 and Notch2, but not Notch4. Furthermore, SFN-mediated inhibition of PC-3 and LNCaP cell migration was only marginally affected by knockdown of Notch1 and Notch2. Strikingly, SFN administration to Transgenic Adenocarcinoma of Mouse Prostate transgenic mice failed to increase levels of cleaved Notch1, cleaved Notch2, and HES-1 proteins in vivo in prostatic intraepithelial neoplasia, well-differentiated carcinoma or poorly-differentiated prostate cancer lesions. These results indicate that Notch activation is largely dispensable for SFN-mediated inhibition of cell

Nano-BCG: A Promising Delivery System for Treatment of Human Bladder Cancer.

Science.gov (United States)

Buss, Julieti Huch; Begnini, Karine Rech; Bender, Camila Bonemann; Pohlmann, Adriana R; Guterres, Silvia S; Collares, Tiago; Seixas, Fabiana Kömmling

2017-01-01

Mycobacterium bovis bacillus Calmette-Guerin (BCG) remains at the forefront of immunotherapy for treating bladder cancer patients. However, the incidence of recurrence and progression to invasive cancer is commonly observed. There are no established effective intravesical therapies available for patients, whose tumors recur following BCG treatment, representing an important unmet clinical need. In addition, there are very limited options for patients who do not respond to or tolerate chemotherapy due to toxicities, resulting in poor overall treatment outcomes. Within this context, nanotechnology is an emergent and promising tool for: (1) controlling drug release for extended time frames, (2) combination therapies due to the ability to encapsulate multiple drugs simultaneously, (3) reducing systemic side effects, (4) increasing bioavailability, (5) and increasing the viability of various routes of administration. Moreover, bladder cancer is often characterized by high mutation rates and over expression of tumor antigens on the tumor cell surface. Therapeutic targeting of these biomolecules may be improved by nanotechnology strategies. In this mini-review, we discuss how nanotechnology can help overcome current obstacles in bladder cancer treatment, and how nanotechnology can facilitate combination chemotherapeutic and BCG immunotherapies for the treatment of non-muscle invasive urothelial bladder cancer.

Nano-BCG: A Promising Delivery System for Treatment of Human Bladder Cancer

Directory of Open Access Journals (Sweden)

Julieti Huch Buss

2018-01-01

Full Text Available Mycobacterium bovis bacillus Calmette–Guerin (BCG remains at the forefront of immunotherapy for treating bladder cancer patients. However, the incidence of recurrence and progression to invasive cancer is commonly observed. There are no established effective intravesical therapies available for patients, whose tumors recur following BCG treatment, representing an important unmet clinical need. In addition, there are very limited options for patients who do not respond to or tolerate chemotherapy due to toxicities, resulting in poor overall treatment outcomes. Within this context, nanotechnology is an emergent and promising tool for: (1 controlling drug release for extended time frames, (2 combination therapies due to the ability to encapsulate multiple drugs simultaneously, (3 reducing systemic side effects, (4 increasing bioavailability, (5 and increasing the viability of various routes of administration. Moreover, bladder cancer is often characterized by high mutation rates and over expression of tumor antigens on the tumor cell surface. Therapeutic targeting of these biomolecules may be improved by nanotechnology strategies. In this mini-review, we discuss how nanotechnology can help overcome current obstacles in bladder cancer treatment, and how nanotechnology can facilitate combination chemotherapeutic and BCG immunotherapies for the treatment of non-muscle invasive urothelial bladder cancer.

Flavonoids as Chemopreventive and Therapeutic Agents Against Lung Cancer

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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

Biological Basis for Chemoprevention of Ovarian Cancer

National Research Council Canada - National Science Library

Berchuck, Andrew

2006-01-01

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

Biomarkers of Selenium Chemoprevention of Prostate Cancer

National Research Council Canada - National Science Library

Dong, Yan

2003-01-01

The purpose of the present study was to examine the mechanism of selenium growth inhibition in PC-3 human prostate cancer cells Selenium retarded cell cycle progression at multiple transition points...

Molecular Mechanisms of Anticancer Effects of Phytoestrogens in Breast Cancer.

Science.gov (United States)

Hsieh, Chia-Jung; Hsu, Ya-Ling; Huang, Ya-Fang; Tsai, Eing-Mei

2018-01-01

Phytoestrogens derived from plants exert estrogenic as well as antiestrogenic effects and multiple actions within breast cancer cells. Chemopreventive properties of phytoestrogens have emerged from epidemiological observations. In recent clinical research studies, phytoestrogens are safe and may even protect against breast cancer. In this brief review, the molecular mechanisms of phytoestrogens on regulation of cell cycle, apoptosis, estrogen receptors, cell signaling pathways, and epigenetic modulations in relation to breast cancer are discussed. Phytoestrogens have a preferential affinity for estrogen receptor (ER)-β, which appears to be associated with antiproliferative and anticarcinogenic effects. Moreover, while phytoestrogens not only inhibit ER-positive but also ER-negative breast cancer cells, the possibility of epigenetic modulation playing an important role is also discussed. In conclusion, as there are multiple targets and actions of phytoestrogens, extensive research is still necessary. However, due to low toxicity, low cost, and easy availability, their potent chemoprevention effects deserve further study. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

New insights into the molecular mechanism of Boletus edulis ribonucleic acid fraction (BE3) concerning antiproliferative activity on human colon cancer cells.

Science.gov (United States)

Lemieszek, Marta Kinga; Ribeiro, Miguel; Marques, Guilhermina; Nunes, Fernando Milheiro; Pożarowski, Piotr; Rzeski, Wojciech

2017-05-24

One of the relatively new and promising strategies of cancer treatment is chemoprevention, which involves the use of natural or synthetic compounds to block, inhibit or reverse carcinogenesis. A valuable and still untapped source of chemopreventive compounds seems to be edible mushrooms belonging to higher Basidiomycetes. Boletus edulis biopolymers extracted with hot water and purified by anion-exchange chromatography showed antiproliferative activity in colon cancer cells, but only fraction BE3, mostly composed of ribonucleic acids, was able to inhibit DNA synthesis in HT-29 cells. The present work aims to elucidate the molecular mechanism of this Boletus edulis ribonucleic acid fraction and in this sense flow cytometry and western blotting were applied to cell cycle analysis in HT-29 cells. We found that the antiproliferative ability of fraction BE3 observed in HT-29 cells was associated with the modulation of expression of cell cycle regulatory proteins (Cyclin D1, Cyclin A, p21 and p27) leading to cell accumulation in the S phase of the cell cycle. Furthermore, the BE3 fraction showed effective silencing of the signal transduction in an MAPK/Erk pathway in HT-29 and LS180 colon cancer cell lines. Thus, the previously and currently obtained results indicate that the BE3 fraction from Boletus edulis has great potential and needs to be further exploited through animal and clinical studies in order to develop a new efficient and safe therapeutic strategy for people who have been threatened by or suffered from colon cancer.

The Role of Resveratrol in Cancer Therapy

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Jeong-Hyeon Ko

2017-12-01

Full Text Available Abstract: Natural product compounds have recently attracted significant attention from the scientific community for their potent effects against inflammation-driven diseases, including cancer. A significant amount of research, including preclinical, clinical, and epidemiological studies, has indicated that dietary consumption of polyphenols, found at high levels in cereals, pulses, vegetables, and fruits, may prevent the evolution of an array of diseases, including cancer. Cancer development is a carefully orchestrated progression where normal cells acquires mutations in their genetic makeup, which cause the cells to continuously grow, colonize, and metastasize to other organs such as the liver, lungs, colon, and brain. Compounds that modulate these oncogenic processes can be considered as potential anti-cancer agents that may ultimately make it to clinical application. Resveratrol, a natural stilbene and a non-flavonoid polyphenol, is a phytoestrogen that possesses anti-oxidant, anti-inflammatory, cardioprotective, and anti-cancer properties. It has been reported that resveratrol can reverse multidrug resistance in cancer cells, and, when used in combination with clinically used drugs, it can sensitize cancer cells to standard chemotherapeutic agents. Several novel analogs of resveratrol have been developed with improved anti-cancer activity, bioavailability, and pharmacokinetic profile. The current focus of this review is resveratrol’s in vivo and in vitro effects in a variety of cancers, and intracellular molecular targets modulated by this polyphenol. This is also accompanied by a comprehensive update of the various clinical trials that have demonstrated it to be a promising therapeutic and chemopreventive agent.

Resveratrol: A review of preclinical studies for human cancer prevention

International Nuclear Information System (INIS)

Athar, Mohammad; Back, Jung Ho; Tang Xiuwei; Kim, Kwang Ho; Kopelovich, Levy; Bickers, David R.; Kim, Arianna L.

2007-01-01

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

Salivary microRNAs as promising biomarkers for detection of esophageal cancer.

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Zijun Xie

Full Text Available BACKGROUND AND PURPOSE: Tissue microRNAs (miRNAs can detect cancers and predict prognosis. Several recent studies reported that tissue, plasma, and saliva miRNAs share similar expression profiles. In this study, we investigated the discriminatory power of salivary miRNAs (including whole saliva and saliva supernatant for detection of esophageal cancer. MATERIALS AND METHODS: By Agilent microarray, six deregulated miRNAs from whole saliva samples from seven patients with esophageal cancer and three healthy controls were selected. The six selected miRNAs were subjected to validation of their expression levels by RT-qPCR using both whole saliva and saliva supernatant samples from an independent set of 39 patients with esophageal cancer and 19 healthy controls. RESULTS: Six miRNAs (miR-10b*, miR-144, miR-21, miR-451, miR-486-5p, and miR-634 were identified as targets by Agilent microarray. After validation by RT-qPCR, miR-10b*, miR-144, and miR-451 in whole saliva and miR-10b*, miR-144, miR-21, and miR-451 in saliva supernatant were significantly upregulated in patients, with sensitivities of 89.7, 92.3, 84.6, 79.5, 43.6, 89.7, and 51.3% and specificities of 57.9, 47.4, 57.9%, 57.9, 89.5, 47.4, and 84.2%, respectively. CONCLUSIONS: We found distinctive miRNAs for esophageal cancer in both whole saliva and saliva supernatant. These miRNAs possess discriminatory power for detection of esophageal cancer. Because saliva collection is noninvasive and convenient, salivary miRNAs show great promise as biomarkers for detection of esophageal cancer in areas at high risk.

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

Seasonal malaria chemoprevention (SMC) is defined as the intermittent administration of full treatment courses of an antimalarial drug to children during the peak of malaria transmission season with the aim of preventing malaria-associated mortality and morbidity. SMC using sulfadoxine-pyrimetham......Seasonal malaria chemoprevention (SMC) is defined as the intermittent administration of full treatment courses of an antimalarial drug to children during the peak of malaria transmission season with the aim of preventing malaria-associated mortality and morbidity. SMC using sulfadoxine......-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...

Potent Skin Cancer Chemopreventing Activity of Some Novel Semi-synthetic Cembranoids from Marine Sources

OpenAIRE

Fahmy, Hesham; Zjawiony, Jordan K.; Konoshima, Takao; Tokuda, Harukuni; Khan, Shabana; Khalifa, Sherief

2006-01-01

Abstract: In the course of our continuing research in development and evaluation of novel skin cancer chemopreventive agents from marine sources, five semi-synthetic cembranoids derived from the marine natural product sarcophine, isolated from the soft coral Sarcophyton glaucum, were synthesized and shown to exhibit a remarkable chemopreventive activity in the in-vitro Epstein Barr Virus Early Antigen (EBV-EA) activation assay. These compounds were assayed in vivo using the two-stage carcinog...

Induction of apoptosis in human breast cancer cell line MCF-7 by ...

African Journals Online (AJOL)

Currently, breast cancer is the leading cause of cancer-related death in women. Therefore, there is an urgent need to develop alternative therapeutic measures against this deadly disease. Many components from dietary or medicinal plants have been identified that possess substantial chemopreventive properties. India has ...

Breast Cancer Biomarkers Based on Nipple and Fine Needle Aspirates

National Research Council Canada - National Science Library

Russo, Irma H

2005-01-01

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

Innovative agents in cancer prevention.

Science.gov (United States)

Manson, Margaret M; Farmer, Peter B; Gescher, Andreas; Steward, William P

2005-01-01

There are many facets to cancer prevention: a good diet, weight control and physical activity, a healthy environment, avoidance of carcinogens such as those in tobacco smoke, and screening of populations at risk to allow early detection. But there is also the possibility of using drugs or naturally occurring compounds to prevent initiation of, or to suppress, tumour growth. Only a few such agents have been used to date in the clinic with any success, and these include non-steroidal anti-inflammatory drugs for colon, finasteride for prostate and tamoxifen or raloxifene for breast tumours. An ideal chemopreventive agent would restore normal growth control to a preneoplastic or cancerous cell population by modifying aberrant signalling pathways or inducing apoptosis (or both) in cells beyond repair. Characteristics for such an agent include selectivity for damaged or transformed cells, good bioavailability and more than one mechanism of action to foil redundancy or crosstalk in signalling pathways. As more research effort is being targeted towards this area, the distinction between chemotherapeutic and chemopreventive agents is blurring. Chemotherapeutic drugs are now being designed to target over- or under-active signalling molecules within cancer cells, a philosophy which is just as relevant in chemoprevention. Development of dietary agents is particularly attractive because of our long-standing exposure to them, their relative lack of toxicity, and encouraging indications from epidemiology. The carcinogenic process relies on the cell's ability to proliferate abnormally, evade apoptosis, induce angiogenesis and metastasise to distant sites. In vitro studies with a number of different diet-derived compounds suggest that there are molecules capable of modulating each of these aspects of tumour growth. However, on the negative side many of them have rather poor bioavailability. The challenge is to uncover their multiple mechanisms of action in order to predict their

New Strategy for Prostate Cancer Prevention Based on Selenium Suppression of Androgen Receptor Signaling

Science.gov (United States)

2010-04-01

combination in prostate cancer chemoprevention. Emodin is a phytochemical that has been shown to induce AR degradation (18). We hypothesize that the...Since the induction of PSA screening , the majority of the prostate cancers diagnosed are asymptomatic, early-stage, small volume diseases. Current

Proteomic profiling reveals that resveratrol inhibits HSP27 expression and sensitizes breast cancer cells to doxorubicin therapy.

Directory of Open Access Journals (Sweden)

José Díaz-Chávez

Full Text Available The use of chemopreventive natural compounds represents a promising strategy in the search for novel therapeutic agents in cancer. Resveratrol (3,4',5-trans-trihydroxystilbilene is a dietary polyphenol found in fruits, vegetables and medicinal plants that exhibits chemopreventive and antitumor effects. In this study, we searched for modulated proteins with preventive or therapeutic potential in MCF-7 breast cancer cells exposed to resveratrol. Using two-dimensional electrophoresis we found significant changes (FC >2.0; p≤0.05 in the expression of 16 proteins in resveratrol-treated MCF-7 cells. Six down-regulated proteins were identified by tandem mass spectrometry (ESI-MS/MS as heat shock protein 27 (HSP27, translationally-controlled tumor protein, peroxiredoxin-6, stress-induced-phosphoprotein-1, pyridoxine-5'-phosphate oxidase-1 and hypoxanthine-guanine phosphoribosyl transferase; whereas one up-regulated protein was identified as triosephosphate isomerase. Particularly, HSP27 overexpression has been associated to apoptosis inhibition and resistance of human cancer cells to therapy. Consistently, we demonstrated that resveratrol induces apoptosis in MCF-7 cells. Apoptosis was associated with a significant increase in mitochondrial permeability transition, cytochrome c release in cytoplasm, and caspases -3 and -9 independent cell death. Then, we evaluated the chemosensitization effect of increasing concentrations of resveratrol in combination with doxorubicin anti-neoplastic agent in vitro. We found that resveratrol effectively sensitize MCF-7 cells to cytotoxic therapy. Next, we evaluated the relevance of HSP27 targeted inhibition in therapy effectiveness. Results evidenced that HSP27 inhibition using RNA interference enhances the cytotoxicity of doxorubicin. In conclusion, our data indicate that resveratrol may improve the therapeutic effects of doxorubicin in part by cell death induction. We propose that potential modulation of HSP27

Proteomic profiling reveals that resveratrol inhibits HSP27 expression and sensitizes breast cancer cells to doxorubicin therapy.

Science.gov (United States)

Díaz-Chávez, José; Fonseca-Sánchez, Miguel A; Arechaga-Ocampo, Elena; Flores-Pérez, Ali; Palacios-Rodríguez, Yadira; Domínguez-Gómez, Guadalupe; Marchat, Laurence A; Fuentes-Mera, Lizeth; Mendoza-Hernández, Guillermo; Gariglio, Patricio; López-Camarillo, César

2013-01-01

The use of chemopreventive natural compounds represents a promising strategy in the search for novel therapeutic agents in cancer. Resveratrol (3,4',5-trans-trihydroxystilbilene) is a dietary polyphenol found in fruits, vegetables and medicinal plants that exhibits chemopreventive and antitumor effects. In this study, we searched for modulated proteins with preventive or therapeutic potential in MCF-7 breast cancer cells exposed to resveratrol. Using two-dimensional electrophoresis we found significant changes (FC >2.0; p≤0.05) in the expression of 16 proteins in resveratrol-treated MCF-7 cells. Six down-regulated proteins were identified by tandem mass spectrometry (ESI-MS/MS) as heat shock protein 27 (HSP27), translationally-controlled tumor protein, peroxiredoxin-6, stress-induced-phosphoprotein-1, pyridoxine-5'-phosphate oxidase-1 and hypoxanthine-guanine phosphoribosyl transferase; whereas one up-regulated protein was identified as triosephosphate isomerase. Particularly, HSP27 overexpression has been associated to apoptosis inhibition and resistance of human cancer cells to therapy. Consistently, we demonstrated that resveratrol induces apoptosis in MCF-7 cells. Apoptosis was associated with a significant increase in mitochondrial permeability transition, cytochrome c release in cytoplasm, and caspases -3 and -9 independent cell death. Then, we evaluated the chemosensitization effect of increasing concentrations of resveratrol in combination with doxorubicin anti-neoplastic agent in vitro. We found that resveratrol effectively sensitize MCF-7 cells to cytotoxic therapy. Next, we evaluated the relevance of HSP27 targeted inhibition in therapy effectiveness. Results evidenced that HSP27 inhibition using RNA interference enhances the cytotoxicity of doxorubicin. In conclusion, our data indicate that resveratrol may improve the therapeutic effects of doxorubicin in part by cell death induction. We propose that potential modulation of HSP27 levels using natural

Grapefruit and its biomedical, antigenotoxic and chemopreventive properties.

Science.gov (United States)

Cristóbal-Luna, José Melesio; Álvarez-González, Isela; Madrigal-Bujaidar, Eduardo; Chamorro-Cevallos, Germán

2018-02-01

Grapefruit (Citrus paradisi Mcfad) is a perenifolium tree 5-6 m high with a fruit of about 15 cm in diameter, protected by the peel we can find about 11-14 segments (carpels), each of which is surrounded by a membrane and each containing the juice sacs, as well as the seeds. The fruit is made up of numerous compounds, and is known to have nutritive value because of the presence of various vitamins and minerals, among other chemicals. The fruit is also used in the field of gastronomy. Information has been accumulated regarding the participation of the fruit structures in a variety of biomedical, antigenotoxic and chemopreventive effects, surely related with the presence of the numerous chemicals that have been determined to constitute the fruit. Such studies have been carried out in different in vitro and in vivo experimental models, and in a few human assays. The information published so far has shown interesting results, therefore, the aims of the present review are to initially examine the main characteristics of the fruit, followed by systematization of the acquired knowledge concerning the biomedical, antigenotoxic and chemopreventive effects produced by the three main structures of the fruit: peel, seed, and pulp. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

Science.gov (United States)

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

Prevention of Post-Radiotherapy Failure in Prostate Cancer by Vitamin D

National Research Council Canada - National Science Library

Vijayakumar, Srinivasan

2005-01-01

.... We propose to have prostate cancer patients who have already undergone radiation treatment take a non-toxic chemopreventive agent A SYNTHETIC FORM OF VITAMIN D, 1alpha-hydroxyvitamin D5 for two years...

Red Wine Polyphenols for Cancer Prevention

OpenAIRE

He, Shan; Sun, Cuirong; Pan, Yuanjiang

2008-01-01

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 ...

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.

Antibody-drug conjugates: Promising and efficient tools for targeted cancer therapy.

Science.gov (United States)

Nasiri, Hadi; Valedkarimi, Zahra; Aghebati-Maleki, Leili; Majidi, Jafar

2018-09-01

Over the recent decades, the use of antibody-drug conjugates (ADCs) has led to a paradigm shift in cancer chemotherapy. Antibody-based treatment of various human tumors has presented dramatic efficacy and is now one of the most promising strategies used for targeted therapy of patients with a variety of malignancies, including hematological cancers and solid tumors. Monoclonal antibodies (mAbs) are able to selectively deliver cytotoxic drugs to tumor cells, which express specific antigens on their surface, and has been suggested as a novel category of agents for use in the development of anticancer targeted therapies. In contrast to conventional treatments that cause damage to healthy tissues, ADCs use mAbs to specifically attach to antigens on the surface of target cells and deliver their cytotoxic payloads. The therapeutic success of future ADCs depends on closely choosing the target antigen, increasing the potency of the cytotoxic cargo, improving the properties of the linker, and reducing drug resistance. If appropriate solutions are presented to address these issues, ADCs will play a more important role in the development of targeted therapeutics against cancer in the next years. We review the design of ADCs, and focus on how ADCs can be exploited to overcome multiple drug resistance (MDR). © 2018 Wiley Periodicals, Inc.

Priorities for the primary prevention of breast cancer.

Science.gov (United States)

Colditz, Graham A; Bohlke, Kari

2014-01-01

Despite recent calls to intensify the search for new risk factors for breast cancer, acting on information that we already have could prevent thousands of cases each year. This article reviews breast cancer primary prevention strategies that are applicable to all women, discusses the underutilization of chemoprevention in high-risk women, highlights the additional advances that could be made by including young women in prevention efforts, and comments on how the molecular heterogeneity of breast cancer affects prevention research and strategies. © 2014 American Cancer Society.

Local delivery of hormonal therapy with silastic tubing for prevention and treatment of breast cancer.

Science.gov (United States)

Park, Jeenah; Thomas, Scott; Zhong, Allison Y; Wolfe, Alan R; Krings, Gregor; Terranova-Barberio, Manuela; Pawlowska, Nela; Benet, Leslie Z; Munster, Pamela N

2018-01-08

Broad use of germline testing has identified an increasing number of women at risk for breast cancer with a need for effective chemoprevention. We report a novel method to selectively deliver various anti-estrogens at high drug levels to the breast tissue by implanting a device comprised of silastic tubing. Optimized tubing properties allow elution of otherwise poorly bioavailable anti-estrogens, such as fulvestrant, into mammary tissue in vitro and in vivo with levels sufficient to inhibit estrogen receptor activation and tumor cell proliferation. Implantable silastic tubing delivers fulvestrant selectively to mouse mammary fat tissue for one year with anti-tumor effects similar to those achieved with systemic fulvestrant exposure. Furthermore, local delivery of fulvestrant significantly decreases cell proliferation, as assessed by Ki67 expression, most effectively in tumor sections adjacent to tubing. This approach may thereby introduce a potential paradigm shift and offer a promising alternative to systemic therapy for prevention and early interception of breast cancer.

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

Directory of Open Access Journals (Sweden)

Chinthalapally V. Rao

2013-09-01

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

Quantitation of chemopreventive synergism between (-)-epigallocatechin-3-gallate and curcumin in normal, premalignant and malignant human oral epithelial cells.

Science.gov (United States)

Khafif, A; Schantz, S P; Chou, T C; Edelstein, D; Sacks, P G

1998-03-01

An in vitro model for oral cancer was used to examine the growth inhibitory effects of chemopreventive agents when used singly and in combination. The model consists of primary cultures of normal oral epithelial cells, newly established cell lines derived from dysplastic leukoplakia and squamous cell carcinoma. Two naturally occurring substances, (-)-epigallocatechin-3-gallate (EGCG) from green tea and curcumin from the spice turmeric were tested. Cells were treated singly and in combination and effects on growth determined in 5-day growth assays and by cell cycle analysis. Effective dose 50s and the combination index were calculated with the computerized Chou-Talalay method which is based on the median-effect principle. Agents were shown to differ in their inhibitory potency. EGCG was less effective with cell progression; the cancer cells were more resistant than normal or dysplastic cells. In contrast, curcumin was equally effective regardless of the cell type tested. Cell cycle analysis indicated that EGCG blocked cells in G1, whereas curcumin blocked cells in S/G2M. The combination of both agents showed synergistic interactions in growth inhibition and increased sigmoidicity (steepness) of the dose-effect curves, a response that was dose and cell type dependent. Combinations allowed for a dose reduction of 4.4-8.5-fold for EGCG and 2.2-2.8-fold for curcumin at ED50s as indicated by the dose reduction index (DRI). Even greater DRI values were observed above ED50 levels. Our results demonstrate that this model which includes normal, premalignant and malignant oral cells can be used to analyse the relative potential of various chemopreventive agents. Two such naturally-occurring agents, EGCG and curcumin, were noted to inhibit growth by different mechanisms, a factor which may account for their demonstrable interactive synergistic effect.

Cytotoxic of Ganoderma lucidum in Colon Cancer through Cyclooxygenase 2 (COX-2 as Its Molecular Target

Directory of Open Access Journals (Sweden)

Agustina Setiawati

2017-05-01

Full Text Available Many studies were designed explore chemopreventive activity of natural products on colon cancer especially addressing COX-2 as molecular target. Another promising source of natural product that potentially exhibit anticancer activity on colon cancer is Ganoderma lucidum. This study assessed selectivity of cytotoxic effect of G. lucidum extract on WiDr to Vero cells and investigated molecular mechanism on COX-2. G. lucidum ex-tract was prepared by reflux extraction method; in vitro anticancer was assayed by MTT method on WiDr and Vero cell line. This study applied apoptosis induction assay to observe cell death mechanism using double staining method; further COX-2 expression was stained by immunocytochemistry method. G. lucidum extract has cytotoxic effect on WiDr cells with IC50 135 µg/mL. However, the cytotoxic effect had low selectivity to-wards Vero cells with Selectivity Index (SI 3.66. The extract induced apoptosis and suppressed COX-2 ex-pression in WiDr cells. G. lucidum extract was potential to be developed as anticancer agent towards colon cancer.

Gamma (γ) tocopherol upregulates peroxisome proliferator activated receptor (PPAR) gamma (γ) expression in SW 480 human colon cancer cell lines

Science.gov (United States)

Campbell, Sharon E; Stone, William L; Whaley, Sarah G; Qui, Min; Krishnan, Koyamangalath

2003-01-01

Background Tocopherols are lipid soluble antioxidants that exist as eight structurally different isoforms. The intake of γ-tocopherol is higher than α-tocopherol in the average US diet. The clinical results of the effects of vitamin E as a cancer preventive agent have been inconsistent. All published clinical trials with vitamin E have used α-tocopherol. Recent epidemiological, experimental and molecular studies suggest that γ-tocopherol may be a more potent chemopreventive form of vitamin E compared to the more-studied α-tocopherol. γ-Tocopherol exhibits differences in its ability to detoxify nitrogen dioxide, growth inhibitory effects on selected cancer cell lines, inhibition of neoplastic transformation in embryonic fibroblasts, and inhibition of cyclooxygenase-2 (COX-2) activity in macrophages and epithelial cells. Peroxisome proliferator activator receptor γ (PPARγ) is a promising molecular target for colon cancer prevention. Upregulation of PPARγ activity is anticarcinogenic through its effects on downstream genes that affect cellular proliferation and apoptosis. The thiazolidine class of drugs are powerful PPARγ ligands. Vitamin E has structural similarity to the thiazolidine, troglitazone. In this investigation, we tested the effects of both α and γ tocopherol on the expression of PPARγ mRNA and protein in SW 480 colon cancer cell lines. We also measured the intracellular concentrations of vitamin E in SW 480 colon cancer cell lines. Results We have discovered that the α and γ isoforms of vitamin E upregulate PPARγ mRNA and protein expression in the SW480 colon cancer cell lines. γ-Tocopherol is a better modulator of PPARγ expression than α-tocopherol at the concentrations tested. Intracellular concentrations increased as the vitamin E concentration added to the media was increased. Further, γ-tocopherol-treated cells have higher intracellular tocopherol concentrations than those treated with the same concentrations of �

Gamma (γ) tocopherol upregulates peroxisome proliferator activated receptor (PPAR) gamma (γ) expression in SW 480 human colon cancer cell lines

International Nuclear Information System (INIS)

Campbell, Sharon E; Stone, William L; Whaley, Sarah G; Qui, Min; Krishnan, Koyamangalath

2003-01-01

Tocopherols are lipid soluble antioxidants that exist as eight structurally different isoforms. The intake of γ-tocopherol is higher than α-tocopherol in the average US diet. The clinical results of the effects of vitamin E as a cancer preventive agent have been inconsistent. All published clinical trials with vitamin E have used α-tocopherol. Recent epidemiological, experimental and molecular studies suggest that γ-tocopherol may be a more potent chemopreventive form of vitamin E compared to the more-studied α-tocopherol. γ-Tocopherol exhibits differences in its ability to detoxify nitrogen dioxide, growth inhibitory effects on selected cancer cell lines, inhibition of neoplastic transformation in embryonic fibroblasts, and inhibition of cyclooxygenase-2 (COX-2) activity in macrophages and epithelial cells. Peroxisome proliferator activator receptor γ (PPARγ) is a promising molecular target for colon cancer prevention. Upregulation of PPARγ activity is anticarcinogenic through its effects on downstream genes that affect cellular proliferation and apoptosis. The thiazolidine class of drugs are powerful PPARγ ligands. Vitamin E has structural similarity to the thiazolidine, troglitazone. In this investigation, we tested the effects of both α and γ tocopherol on the expression of PPARγ mRNA and protein in SW 480 colon cancer cell lines. We also measured the intracellular concentrations of vitamin E in SW 480 colon cancer cell lines. We have discovered that the α and γ isoforms of vitamin E upregulate PPARγ mRNA and protein expression in the SW480 colon cancer cell lines. γ-Tocopherol is a better modulator of PPARγ expression than α-tocopherol at the concentrations tested. Intracellular concentrations increased as the vitamin E concentration added to the media was increased. Further, γ-tocopherol-treated cells have higher intracellular tocopherol concentrations than those treated with the same concentrations of α-tocopherol. Our data suggest that

Effects of Brassicaceae Isothiocyanates on Prostate Cancer

Directory of Open Access Journals (Sweden)

Silvia Novío

2016-05-01

Full Text Available Despite the major progress made in the field of cancer biology, cancer is still one of the leading causes of mortality, and prostate cancer (PCa is one of the most encountered malignancies among men. The effective management of this disease requires developing better anticancer agents with greater efficacy and fewer side effects. Nature is a large source for the development of chemotherapeutic agents, with more than 50% of current anticancer drugs being of natural origin. Isothiocyanates (ITCs are degradation products from glucosinolates that are present in members of the family Brassicaceae. Although they are known for a variety of therapeutic effects, including antioxidant, immunostimulatory, anti-inflammatory, antiviral and antibacterial properties, nowadays, cell line and animal studies have additionally indicated the chemopreventive action without causing toxic side effects of ITCs. In this way, they can induce cell cycle arrest, activate apoptosis pathways, increase the sensitivity of resistant PCa to available chemodrugs, modulate epigenetic changes and downregulate activated signaling pathways, resulting in the inhibition of cell proliferation, progression and invasion-metastasis. The present review summarizes the chemopreventive role of ITCs with a particular emphasis on specific molecular targets and epigenetic alterations in in vitro and in vivo cancer animal models.

Resveratrol for breast cancer prevention and therapy: Preclinical evidence and molecular mechanisms.

Science.gov (United States)

Sinha, Dona; Sarkar, Nivedita; Biswas, Jaydip; Bishayee, Anupam

2016-10-01

Globally, breast cancer is the most frequently diagnosed cancer among women. The major unresolved problems with metastatic breast cancer is recurrence after receiving objective response to chemotherapy, drug-induced side effects of first line chemotherapy and delayed response to second line of treatment. Unfortunately, very few options are available as third line treatment. It is clear that under such circumstances there is an urgent need for new and effective drugs. Phytochemicals are among the most promising chemopreventive treatment options for the management of cancer. Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a non-flavonoid polyphenol present in several dietary sources, including grapes, berries, soy beans, pomegranate and peanuts, has been shown to possess a wide range of health benefits through its effect on a plethora of molecular targets.The present review encompasses the role of resveratrol and its natural/synthetic analogue in the light of their efficacy against tumor cell proliferation, metastasis, epigenetic alterations and for induction of apoptosis as well as sensitization toward chemotherapeutic drugs in various in vitro and in vivo models of breast cancer. The roles of resveratrol as a phytoestrogen, an aromatase inhibitor and in stem cell therapy as well as adjuvent treatment are also discussed. This review explores the full potential of resveratrol in breast cancer prevention and treatment with current limitations, challenges and future directions of research. Copyright © 2016 Elsevier Ltd. All rights reserved.

ACTOplus Met XR in Treating Patients With Stage I-IV Oral Cavity or Oropharynx Cancer Undergoing Definitive Treatment | Division of Cancer Prevention

Science.gov (United States)

This randomized phase IIb trial studies how well ACTOplus met XR works in treating in patients with stage I-IV oral cavity or oropharynx cancer that are undergoing definitive treatment. Chemoprevention is the use of drugs to keep oral cavity or oropharynx cancer from forming or coming back. The use of ACTOplus met XR may slow disease progression in patients with oral cavity or

Prevention of ovarian cancer.

Science.gov (United States)

Hanna, Louise; Adams, Malcolm

2006-04-01

Ovarian cancer is the leading cause of death from gynaecological malignancy. The incidence is high in the Western world. The incidence of ovarian cancer is reduced by pregnancy, lactation, the oral contraceptive pill and tubal ligation. Lifestyle factors are important in the aetiology of ovarian cancer and current evidence suggests the risk can be reduced by eating a diet rich in fruit and vegetables, taking regular exercise, avoiding smoking, avoiding being overweight and avoiding long-term use of hormonal replacement therapy (HRT). Familial ovarian cancer is responsible for about 10% of ovarian cancer cases. Strategies available to high-risk women include screening (covered elsewhere) and prophylactic salpingo-oophorectomy. The precise role of chemoprevention for high-risk women in the form of the oral contraceptive pill is unclear.

Effect of a vegan diet on biomarkers of chemoprevention in females

NARCIS (Netherlands)

Verhagen, H.; Rauma, A.L.; Törrönen, R.; Vogel, N. de; Bruijntjes-Rozier, G.C.D.M.; Dreve, M.A.; Bogaards, J.J.P.; Mykkänen, H.

1996-01-01

1. In order to study the potential beneficial effects of a vegan diet, a cross-sectional study was performed and several biomarkers of chemoprevention were measured in a population of female 'living food' eaters ('vegans'; n = 20) vs matched omnivorous controls (n = 20). 2. White blood cells

The promise of molecular epidemiology in defining the association between radiation and cancer

International Nuclear Information System (INIS)

Neta, R.

2000-01-01

Molecular epidemiology involves the inclusion in epidemiologic studies of biologic measurements made at a genetic and molecular level and aims to improve the current knowledge of disease etiology and risk. One of the goals of molecular epidemiology studies of cancer is to determine the role of environmental and genetic factors in initiation and progression of malignancies and to use this knowledge to develop preventive strategies. This approach promises extraordinary opportunities for revolutionizing the practice of medicine and reducing risk. However, this will be accompanied by the need to address and resolve many challenges, such as ensuring the appropriate interpretation of molecular testing and resolving associated ethical, legal, and social issues. Traditional epidemiologic approaches determined that exposure to ionizing radiation poses significantly increased risk of leukemia and several other types of cancer. Such studies provided the basis for setting exposure standards to protect the public and the workforce from potentially adverse effects of ionizing radiation. These standards were set by using modeling approaches to extrapolate from the biological effects observed in high-dose radiation studies to predicted, but mostly immeasurable, effects at low radiation doses. It is anticipated that the addition of the molecular parameters to the population-based studies will help identify the genes and pathways characteristic of cancers due to radiation exposure of individuals, as well as identify susceptible or resistant subpopulations. In turn, the information about the molecular mechanisms should aid to improve risk assessment. While studies on radiogenic concerns are currently limited to only a few candidate genes, the exponential growth of scientific knowledge and technology promises expansion of knowledge about identity of participating genes and pathways in the future. This article is meant to provide an introductory overview of recent advances in

Nutrients, Foods, and Colorectal Cancer Prevention

OpenAIRE

Song, Mingyang; Garrett, Wendy S.; Chan, Andrew T.

2015-01-01

Diet has an important role in the development of colorectal cancer. In the past few decades, findings from extensive epidemiologic and experimental investigation have linked consumption of several foods and nutrients to the risk of colorectal neoplasia. Calcium, fiber, milk, and whole grain have been associated with a lower risk of colorectal cancer, and red meat and processed meat with an increased risk. There is substantial evidence for the potential chemopreventive effects of vitamin D, fo...

Lunasin-aspirin combination against NIH/3T3 cells transformation induced by chemical carcinogens.

Science.gov (United States)

Hsieh, Chia-Chien; Hernández-Ledesma, Blanca; de Lumen, Ben O

2011-06-01

Carcinogenesis is a multistage process involving a number of molecular pathways sensitive to intervention. Chemoprevention is defined as the use of natural and/or synthetic substances to block, reverse, or retard the process of carcinogenesis. To achieve greater inhibitory effects on cancer cells, combination of two or more chemopreventive agents is commonly considered as a better preventive and/or therapeutic strategy. Lunasin is a promising cancer preventive peptide identified in soybean and other seeds. Its efficacy has been demonstrated by both in vitro and in vivo models. This peptide has been found to inhibit human breast cancer MDA-MB-231 cells proliferation, suppressing cell cycle progress and inducing cell apoptosis. Moreover, lunasin potentiates the effects on these cells of different synthetic and natural compounds, such as aspirin and anacardic acid. This study explored the role of lunasin, alone and in combination with aspirin and anacardic acid on cell proliferation and foci formation of transformed NIH/3T3 cells induced by chemical carcinogens 7,12-dimethylbenz[a]anthracene or 3-methylcholanthrene. The results revealed that lunasin, acting as a single agent, inhibits cell proliferation and foci formation. When combined with aspirin, these effects were significantly increased, indicating that this combination might be a promising strategy to prevent/treat cancer induced by chemical carcinogens.

The selective estrogen receptor modulators in breast cancer prevention.

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Li, Fangxuan; Dou, Jinli; Wei, Lijuan; Li, Shixia; Liu, Juntian

2016-05-01

Persistently increased blood levels of estrogens are associated with an increased risk of breast cancer. Selective estrogen receptor modulators (SERMs) are a class of compounds that act on the estrogen receptor (ER). Several clinical trials have demonstrated the effectiveness of its prophylactic administration. Incidence of invasive ER-positive breast cancer was reduced by SERMs treatment, especially for those women with high risk of developing breast cancer. In this study, we reviewed the clinical application of SERMs in breast cancer prevention. To date, four prospective randomized clinical trials had been performed to test the efficacy of tamoxifen for this purpose. Concerning on the benefit and cost of tamoxifen, various studies from different countries demonstrated that chemoprevention with tamoxifen seemed to be cost-effective for women with a high risk of invasive breast cancer. Based above, tamoxifen was approved for breast cancer prevention by the US Food and Drug Administration in 1998. Raloxifene was also approved for postmenopausal women in 2007 for breast cancer prevention which reduces the risk of invasive breast cancer with a lower risk of unwanted stimulation of endometrium. Thus, raloxifene is considered to have a better clinical possesses as prophylactic agent. Several other agents, such as arzoxifene and lasofoxifene, are currently being investigated in clinic. The American Society of Clinical Oncology and National Comprehensive Cancer Network had published guidelines on breast cancer chemoprevention by SERMs. However, use of tamoxifen and raloxifene for primary breast cancer prevention was still low. A broader educational effort is needed to alert women and primary care physicians that SERMs are available to reduce breast cancer risk.

Nanoparticles for cancer imaging: The good, the bad, and the promise

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Chapman, Sandra; Dobrovolskaia, Marina; Farahani, Keyvan; Goodwin, Andrew; Joshi, Amit; Lee, Hakho; Meade, Thomas; Pomper, Martin; Ptak, Krzysztof; Rao, Jianghong; Singh, Ravi; Sridhar, Srinivas; Stern, Stephan; Wang, Andrew; Weaver, John B.; Woloschak, Gayle; Yang, Lily

2014-01-01

Summary Recent advances in molecular imaging and nanotechnology are providing new opportunities for biomedical imaging with great promise for the development of novel imaging agents. The unique optical, magnetic, and chemical properties of materials at the scale of nanometers allow the creation of imaging probes with better contrast enhancement, increased sensitivity, controlled biodistribution, better spatial and temporal information, multi-functionality and multi-modal imaging across MRI, PET, SPECT, and ultrasound. These features could ultimately translate to clinical advantages such as earlier detection, real time assessment of disease progression and personalized medicine. However, several years of investigation into the application of these materials to cancer research has revealed challenges that have delayed the successful application of these agents to the field of biomedical imaging. Understanding these challenges is critical to take full advantage of the benefits offered by nano-sized imaging agents. Therefore, this article presents the lessons learned and challenges encountered by a group of leading researchers in this field, and suggests ways forward to develop nanoparticle probes for cancer imaging. Published by Elsevier Ltd. PMID:25419228

Combined Gemcitabine and Metronidazole Is a Promising Therapeutic Strategy for Cancer Stem-like Cholangiocarcinoma.

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Kawamoto, Makoto; Umebayashi, Masayo; Tanaka, Hiroto; Koya, Norihiro; Nakagawa, Sinichiro; Kawabe, Ken; Onishi, Hideya; Nakamura, Masafumi; Morisaki, Takashi

2018-05-01

Metronidazole (MNZ) is a common antibiotic that exerts disulfiram-like effects when taken together with alcohol. However, the relationship between MNZ and aldehyde dehydrogenase (ALDH) activity remains unclear. This study investigated whether MNZ reduces cancer stemness by suppressing ALDH activity and accordingly reducing the malignancy of cholangiocarcinoma (CCA). We developed gemcitabine (GEM)-resistant TFK-1 cells and originally established CCA cell line from a patient with GEM-resistant CCA. Using these cell lines, we analyzed the impacts of MNZ for cancer stem cell markers, invasiveness, and chemosensitivity. MNZ reduced ALDH activity in GEM-resistant CCA cells, leading to decreased invasiveness and enhanced chemosensitivity. MNZ diminished the invasiveness by inducing mesenchymal-epithelial transition and enhancing chemosensitivity by increasing ENT1 (equilibrative nucleoside transporter 1) and reducing RRM1 (ribonucleotide reductase M1). MNZ reduced cancer stemness in GEM-resistant CCA cells. Combined GEM and MNZ would be a promising therapeutic strategy for cancer stem-like CAA. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Norathyriol Suppresses Skin Cancers Induced by Solar Ultraviolet Radiation by Targeting ERK Kinases

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Li, Jixia; Malakhova, Margarita; Mottamal, Madhusoodanan; Reddy, Kanamata; Kurinov, Igor; Carper, Andria; Langfald, Alyssa; Oi, Naomi; Kim, Myoung Ok; Zhu, Feng; Sosa, Carlos P.; Zhou, Keyuan; Bode, Ann M.; Dong, Zigang (Cornell); (Guangdong); (UMM)

2012-06-27

Ultraviolet (UV) irradiation is the leading factor in the development of skin cancer, prompting great interest in chemopreventive agents for this disease. In this study, we report the discovery of norathyriol, a plant-derived chemopreventive compound identified through an in silico virtual screening of the Chinese Medicine Library. Norathyriol is a metabolite of mangiferin found in mango, Hypericum elegans, and Tripterospermum lanceolatum and is known to have anticancer activity. Mechanistic investigations determined that norathyriol acted as an inhibitor of extracellular signal-regulated kinase (ERK)1/2 activity to attenuate UVB-induced phosphorylation in mitogen-activated protein kinases signaling cascades. We confirmed the direct and specific binding of norathyriol with ERK2 through a cocrystal structural analysis. The xanthone moiety in norathyriol acted as an adenine mimetic to anchor the compound by hydrogen bonds to the hinge region of the protein ATP-binding site on ERK2. Norathyriol inhibited in vitro cell growth in mouse skin epidermal JB6 P+ cells at the level of G{sub 2}-M phase arrest. In mouse skin tumorigenesis assays, norathyriol significantly suppressed solar UV-induced skin carcinogenesis. Further analysis indicated that norathyriol mediates its chemopreventive activity by inhibiting the ERK-dependent activity of transcriptional factors AP-1 and NF-{kappa}B during UV-induced skin carcinogenesis. Taken together, our results identify norathyriol as a safe new chemopreventive agent that is highly effective against development of UV-induced skin cancer.

Plant derived substances with anti-cancer activity: from folklore to practice

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Marcelo eFridlender

2015-10-01

Full Text Available Plants have had an essential role in the folklore of ancient cultures. In addition to the use as food and spices, plants have also been utilized as medicines for over 5000 years. It is estimated that 70-95% of the population in developing countries continues to use traditional medicines even today. A new trend, that involved the isolation of plant active compounds begun during the early 19th century. This trend led to the discovery of different active compounds that are derived from plants. In the last decades, more and more new materials derived from plants have been authorized and subscribed as medicines, including those with anti-cancer activity. Cancer is among the leading causes of morbidity and mortality worldwide. The number of new cases is expected to rise by about 70% over the next 2 decades. Thus, there is a real need for new efficient anti-cancer drugs with reduced side effects, and plants are a promising source for such entities. Here we focus on some plant-derived substances exhibiting anti-cancer and chemoprevention activity, their mode of action and bioavailability. These include paclitaxel, curcumin and cannabinoids. In addition, development and use of their synthetic analogs, and those of strigolactones, are discussed. Also discussed are commercial considerations and future prospects for development of plant derived substances with anti-cancer activity.

Biological Basis for Chemoprevention of Ovarian Cancer

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2006-10-01

Concealing Clothing” Sukru Hatun, Omer Islam, Filiz Cizmecioglu, Bulent Kara, Kadir Babaoglu, Fatma Berk,and Ayse Sevim Go¨ kalp J. Nutr. 135: 218–222...to studies in ovarian caner , analyses of the relationship between the short AR CAG repeat length polymorphism and prostate cancer risk also have...pregnant, months of OC use, BMI, tubal ligation, family history of breast or ovarian caner in a first degree relative, waist-to-hip ratio 23 Table 6

Dietary intake of total polyphenol and polyphenol classes and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

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Zamora-Ros, Raul; Cayssials, Valerie; Jenab, Mazda

2018-01-01

Polyphenols may play a chemopreventive role in colorectal cancer (CRC); however, epidemiological evidence supporting a role for intake of individual polyphenol classes, other than flavonoids is insufficient. We evaluated the association between dietary intakes of total and individual classes and ...

In Vitro and Ex Vivo Chemopreventive Action of Mauritia flexuosa Products

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Joilane Alves Pereira-Freire

2018-01-01

Full Text Available Mauritia flexuosa (Arecaceae, known as “Buriti,” is a Brazilian palm tree with high economic potential for local communities. Herein, we investigated the phytochemistry profile and antioxidant potential of M. flexuosa fruits and determined the bioaccessibility of phenolic compounds. Peels revealed upper values for phenols, flavonoids, carotenoids, tannins, and ascorbic acid when compared to the pulps and endocarps. All samples showed capacity to scavenger free radicals (0.5, 1.0, 2.0, 4.0, and 8.0 mg/mL but peels presented higher scavenger action in all methods explored. Phenolic compounds identified by HPLC displayed reduced bioaccessibility after in vitro simulated gastrointestinal digestion for pulp (38.7%, peel (18.7%, and endocarp (22.3% extracts (P<0.05. Buriti fruits also protected rat blood cells against lysis induced by peroxyl radicals. We demonstrated the promising chemopreventive potentialities of M. flexuosa fruits and their by-products and peels with higher quantities of bioactive compounds and phenolic substances before and after in vitro bioaccessibility investigation. In Brazil, these parts are discarded or underused, mainly as feed for ruminant animals. Consequently, it is extremely important to explore nutritional characteristics of these by-products for human/livestock foods and to install biofriendly techniques and sustainable biotechnology handling of natural resources.

A smart pH-responsive nano-carrier as a drug delivery system for the targeted delivery of ursolic acid: suppresses cancer growth and metastasis by modulating P53/MMP-9/PTEN/CD44 mediated multiple signaling pathways.

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Jiang, Kai; Chi, Ting; Li, Tao; Zheng, Guirong; Fan, Lulu; Liu, Yajun; Chen, Xiufen; Chen, Sijia; Jia, Lee; Shao, Jingwei

2017-07-13

Ursolic acid (UA) has been recently used as a promising anti-tumor and cancer metastatic chemo-preventive agent due to its low toxicity and liver-protecting property. However, the low bioavailability and nonspecific tumor targeting restrict its further clinical application. To address the problem, a silica-based mesoporous nanosphere (MSN) controlled-release drug delivery system (denoted UA@M-CS-FA) was designed and successfully synthesized, and was functionalized with folic acid (FA) and pH-sensitive chitosan (CS) for the targeted delivery of UA to folate receptor (FR) positive tumor cells. UA@M-CS-FA were spherical with mean diameter below 150 nm, and showed about -20 mV potential. Meanwhile, UA@M-CS-FA exhibited a pH-sensitive release manner and high cellular uptake in FR over-expressing HeLa cancer cells. Also, in vitro cellular assays suggested that UA@M-CS-FA inhibited cancer cell growth, invasion and migration. Mechanistically, UA@M-CS-FA induced cancer cell apoptosis and inhibited migration via cell cycle arrest in the G0/G1 stage, regulating the PARP/Bcl-2/MMP-9/CD44/PTEN/P53. Importantly, in vivo experiments further confirmed that UA@M-CS-FA significantly suppressed the tumor progression and lung metastasis in tumor-bearing nude mice. Immunohistochemical analysis revealed that UA@M-CS-FA treatment regulated CD44, a biomarker of cancer metastasis. Overall, our data demonstrated that a CS and FA modified MSN controlled-release drug delivery system could help broaden the usage of UA and reflect the great application potential of the UA as an anticancer or cancer metastatic chemopreventive agent.

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

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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...

MicroRNA: a new and promising potential biomarker for diagnosis and prognosis of ovarian cancer

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Pal, Manish K.; Jaiswar, Shyam P.; Dwivedi, Vinaya N.; Tripathi, Amit K.; Dwivedi, Ashish; Sankhwar, Pushplata

2015-01-01

Epithelial ovarian cancer (EOC) is the leading cause of death among all gynecological malignancies. Despite the technological and medical advances over the past four decades, such as the development of several biological markers (mRNA and proteins biomarkers), the mortality rate of ovarian cancer remains a challenge because of its late diagnosis, which is specifically attributed to low specificities and sensitivities. Under this compulsive scenario, recent advances in expression biology have shifted in identifying and developing specific and sensitive biomarkers, such as microRNAs (miRNAs) for cancer diagnosis and prognosis. MiRNAs are a novel class of small non-coding RNAs that deregulate gene expression at the posttranscriptional level, either by translational repression or by mRNA degradation. These mechanisms may be involved in a complex cascade of cellular events associated with the pathophysiology of many types of cancer. MiRNAs are easily detectable in tissue and blood samples of cancer patients. Therefore, miRNAs hold good promise as potential biomarkers in ovarian cancer. In this review, we attempted to provide a comprehensive profile of key miRNAs involved in ovarian carcinoma to establish miRNAs as more reliable non-invasive clinical biomarkers for early detection of ovarian cancer compared with protein and DNA biomarkers

Polyphenol-rich extract of Pimenta dioica berries (Allspice) kills breast cancer cells by autophagy and delays growth of triple negative breast cancer in athymic mice

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Zhang, Lei; Shamaladevi, Nagarajarao; Jayaprakasha, Guddadarangavvanahally K.; Patil, Bhimu S.; Lokeshwar, Bal L.

2015-01-01

Bioactive compounds from edible plants have limited efficacy in treating advanced cancers, but they have potential to increase the efficacy of chemotherapy drugs in a combined treatment. An aqueous extract of berries of Pimenta dioica (Allspice) shows promise as one such candidate for combination therapy or chemoprevention. An aqueous extract of Allspice (AAE) was tested against human breast cancer (BrCa) cells in vitro and in vivo. AAE reduced the viability and clonogenic growth of several types of BrCa cells (IC50 ≤ 100 μg/ml) with limited toxicity in non-tumorigenic, quiescent cells (IC50 >200 μg/ml). AAE induced cytotoxicity in BrCa was inconsistent with apoptosis, but was associated with increased levels of autophagy markers LC3B and LC3B-positive puncta. Silencing the expression of autophagy related genes (ATGs) prevented AAE-induced cell death. Further, AAE caused inhibition of Akt/mTOR signaling, and showed enhanced cytotoxicity when combined with rapamycin, a chemotherapy drug and an inhibitor of mTOR signaling. Oral administration (gavage) of AAE into athymic mice implanted with MDA-MB231 tumors inhibited tumor growth slightly but not significantly (mean decrease ~ 14%, p ≥ 0.20) if mice were gavaged post-tumor implant. Tumor growth showed a significant delay (38%) in tumor palpability and growth rate (time to reach tumor volume ≥ 1,000 mm3) when mice were pre-dosed with AAE for two weeks. Analysis of tumor tissues showed increased levels of LC3B in AAE treated tumors, indicating elevated autophagic tumor cell death in vivo in treated mice. These results demonstrate antitumor and chemo-preventive activity of AAE against BrCa and potential for adjuvant to mTOR inhibition. PMID:25945840

Polyphenols in Food: Cancer Prevention and Apoptosis Induction.

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Sharma, Ashita; Kaur, Mandeep; Katnoria, Jatinder Kaur; Nagpal, Avinash Kaur

2017-10-06

Polyphenols are group of water-soluble organic compounds, mainly of natural origin. The compounds having about 5-7 aromatic rings and more than 12 phenolic hydroxyl groups are classified as polyphenols. These are the antioxidants which protect the body from oxidative damage. In plants, they are the secondary metabolites produced as a defense mechanism against stress factors. Antioxidant property of polyphenols is suggested to provide protection against many diseases associated with reactive oxygen species (ROS), including cancer. Various studies carried out across the world have suggested that polyphenols can inhibit the tumor generation, induce apoptosis in cancer cells and interfere in progression of tumors. This group of wonder compounds is present in surplus in natural plants and food products. Intake of polyphenols through diet can scavenge ROS and thus can help in cancer prevention. The plant derived products can also be used along with conventional chemotherapy to enhance the chemopreventive effects. The present review focuses on various in vitro and in vivo studies carried out to assess the anti-carcinogenic potential of polyphenols present in our food. Also, the pathways involved in cancer chemopreventive effects of various subclasses (flavonoids, lignans, stilbenes and phenolic acids) of polyphenols are discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid has enhanced chemo-preventive properties compared to aspirin, is gastrointestinal safe with all the classic therapeutic indications

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Kodela, Ravinder; Chattopadhyay, Mitali; Velázquez-Martínez, Carlos A.; Kashfi, Khosrow

2015-01-01

Aspirin is chemopreventive; however, side effects preclude its long-term use. NOSH-aspirin (NBS-1120), a novel hybrid that releases nitric oxide and hydrogen sulfide, was designed to be a safer alternative. Here we compare the gastrointestinal safety, anti-inflammatory, analgesic, antipyretic, anti-platelet, and chemopreventive properties of aspirin and NBS-1120 administered orally to rats at equimolar doses. Gastrointestinal safety: 6h post-administration, the number and size of hemorrhagic lesions in stomachs were counted; tissue samples were frozen for PGE2, SOD, and MDA determination. Anti-inflammatory: 1h after drug administration, the volume of carrageenan-induced rat paw edemas was measured for 5h. Anti-pyretic: fever was induced by LPS (ip) an hour before administration of the test drugs, core body temperature was measured hourly for 5h. Analgesic: time-dependent analgesic effects were evaluated by carrageenan-induced hyperalgesia. Antiplatelet: anti-aggregatory effects were studied on collagen-induced platelet aggregation of human platelet-rich plasma. Chemoprevention: Nude mice were gavaged daily for 25 days with vehicle, aspirin or NBS-1120. After one week, each mouse was inoculated subcutaneously in the right flank with HT-29 human colon cancer cells. Both agents reduced PGE2 levels in stomach tissue; however, NBS-1120 did not cause any stomach ulcers, whereas aspirin caused significant bleeding. Lipid peroxidation induced by aspirin was higher than that exerted by NBS-1120. SOD activity was significantly inhibited by aspirin but increased by NBS-1120. Both agents showed similar anti-inflammatory, analgesic, anti-pyretic, and anti-platelet activities. Aspirin increased plasma TNFα more than NBS-1120-treated animals. NBS-1120 was better than aspirin as a chemopreventive agent; it dose-dependently inhibited tumor growth and tumor mass. PMID:26394025

Metformin: Multi-faceted protection against cancer

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Cufí, Sílvia; Oliveras-Ferraros, Cristina; Bosch-Barrera, Joaquim; Joven, Jorge; Martin-Castillo, Begoña; Menendez, Javier A.

2011-01-01

The biguanide metformin, a widely used drug for the treatment of type 2 diabetes, may exert cancer chemopreventive effects by suppressing the transformative and hyperproliferative processes that initiate carcinogenesis. Metformin's molecular targets in cancer cells (e.g., mTOR, HER2) are similar to those currently being used for directed cancer therapy. However, metformin is nontoxic and might be extremely useful for enhancing treatment efficacy of mechanism-based and biologically targeted drugs. Here, we first revisit the epidemiological, preclinical, and clinical evidence from the last 5 years showing that metformin is a promising candidate for oncology therapeutics. Second, the anticancer effects of metformin by both direct (insulin-independent) and indirect (insulin-dependent) mechanisms are discussed in terms of metformin-targeted processes and the ontogenesis of cancer stem cells (CSC), including Epithelial-to-Mesenchymal Transition (EMT) and microRNAs-regulated dedifferentiation of CSCs. Finally, we present preliminary evidence that metformin may regulate cellular senescence, an innate safeguard against cellular immortalization. There are two main lines of evidence that suggest that metformin's primary target is the immortalizing step during tumorigenesis. First, metformin activates intracellular DNA damage response checkpoints. Second, metformin attenuates the anti-senescence effects of the ATP-generating glycolytic metabotype-the Warburg effect-, which is required for self-renewal and proliferation of CSCs. If metformin therapy presents an intrinsic barrier against tumorigenesis by lowering the threshold for stress-induced senescence, metformin therapeutic strategies may be pivotal for therapeutic intervention for cancer. Current and future clinical trials will elucidate whether metformin has the potential to be used in preventive and treatment settings as an adjuvant to current cancer therapeutics. PMID:22203527

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

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

2014-10-01

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

A Phase I Safety, Pharmacokinetic, and Pharmacodynamic Presurgical Trial of Vitamin E δ-tocotrienol in Patients with Pancreatic Ductal Neoplasia

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Gregory M. Springett

2015-12-01

Interpretation: VEDT from 200 to 1600 mg daily taken orally for 2 weeks before pancreatic surgery was well tolerated, reached bioactive levels in blood, and significantly induced apoptosis in the neoplastic cells of patients with pancreatic ductal neoplasia. These promising results warrant further clinical investigation of VEDT for chemoprevention and/or therapy of pancreatic cancer.

Mouse Models for Studying Oral Cancer: Impact in the Era of Cancer Immunotherapy.

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Luo, J J; Young, C D; Zhou, H M; Wang, X J

2018-04-01

Model systems for oral cancer research have progressed from tumor epithelial cell cultures to in vivo systems that mimic oral cancer genetics, pathological characteristics, and tumor-stroma interactions of oral cancer patients. In the era of cancer immunotherapy, it is imperative to use model systems to test oral cancer prevention and therapeutic interventions in the presence of an immune system and to discover mechanisms of stromal contributions to oral cancer carcinogenesis. Here, we review in vivo mouse model systems commonly used for studying oral cancer and discuss the impact these models are having in advancing basic mechanisms, chemoprevention, and therapeutic intervention of oral cancer while highlighting recent discoveries concerning the role of immune cells in oral cancer. Improvements to in vivo model systems that highly recapitulate human oral cancer hold the key to identifying features of oral cancer initiation, progression, and invasion as well as molecular and cellular targets for prevention, therapeutic response, and immunotherapy development.

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

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Ching-Chuan Kuo, Ph.D.

2012-10-01

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

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...

A Systematic Review of Promising Strategies of Faith-Based Cancer Education and Lifestyle Interventions Among Racial/Ethnic Minority Groups.

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Hou, Su-I; Cao, Xian

2017-09-13

Church-based interventions have been used to reach racial/ethnic minorities. In order to develop effective programs, we conducted a comprehensive systematic review of faith-based cancer prevention studies (2005~2016) to examine characteristics and promising strategies. Combination terms "church or faith-based or religion," "intervention or program," and "cancer education or lifestyle" were used in searching the five major databases: CINAHL; ERIC; Health Technology Assessments; MEDLINE; and PsycInfo. A total of 20 studies met study criteria. CDC's Community Guide was used to analyze and review group interventions. Analyses were organized by two racial groups: African American (AA) and Latino/Hispanic American groups. Results showed most studies reviewed focused on breast cancer alone or in combination with other cancers. Studies of Latino/Hispanic groups targeted more on uninsured, Medicare, or Medicaid individuals, whereas AA studies generally did not include specific insurance criteria. The sample sizes of the AA studies were generally larger. The majority of these studies reviewed used pre-post, posttest only with control group, or quasi-experience designs. The Health Belief Model was the most commonly used theory in both groups. Community-based participatory research and empowerment/ecological frameworks were also used frequently in the Latino/Hispanic studies. Small media and group education were the top two most popular intervention strategies in both groups. Although one-on-one strategy was used in some Latino studies, neither group used reducing client out-of-pocket costs strategy. Client reminders could also be used more in both groups as well. Current review showed church-based cancer education programs were effective in changing knowledge, but not always screening utilization. Results show faith-based cancer educational interventions are promising. To maximize intervention impact, future studies might consider using stronger study designs, incorporating a

Differentiation of breast cancer stem cells by knockdown of CD44: promising differentiation therapy

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Pham Phuc V

2011-12-01

Full Text Available Abstract Background Breast cancer stem cells (BCSCs are the source of breast tumors. Compared with other cancer cells, cancer stem cells show high resistance to both chemotherapy and radiotherapy. Targeting of BCSCs is thus a potentially promising and effective strategy for breast cancer treatment. Differentiation therapy represents one type of cancer stem-cell-targeting therapy, aimed at attacking the stemness of cancer stem cells, thus reducing their chemo- and radioresistance. In a previous study, we showed that down-regulation of CD44 sensitized BCSCs to the anti-tumor agent doxorubicin. This study aimed to determine if CD44 knockdown caused BCSCs to differentiate into breast cancer non-stem cells (non-BCSCs. Methods We isolated a breast cancer cell population (CD44+CD24- cells from primary cultures of malignant breast tumors. These cells were sorted into four sub-populations based on their expression of CD44 and CD24 surface markers. CD44 knockdown in the BCSC population was achieved using small hairpin RNA lentivirus particles. The differentiated status of CD44 knock-down BCSCs was evaluated on the basis of changes in CD44+CD24- phenotype, tumorigenesis in NOD/SCID mice, and gene expression in relation to renewal status, metastasis, and cell cycle in comparison with BCSCs and non-BCSCs. Results Knockdown of CD44 caused BCSCs to differentiate into non-BCSCs with lower tumorigenic potential, and altered the cell cycle and expression profiles of some stem cell-related genes, making them more similar to those seen in non-BCSCs. Conclusions Knockdown of CD44 is an effective strategy for attacking the stemness of BCSCs, resulting in a loss of stemness and an increase in susceptibility to chemotherapy or radiation. The results of this study highlight a potential new strategy for breast cancer treatment through the targeting of BCSCs.

A novel shogaol analog suppresses cancer cell invasion and inflammation, and displays cytoprotective effects through modulation of NF-κB and Nrf2-Keap1 signaling pathways

Energy Technology Data Exchange (ETDEWEB)

Gan, Fei-Fei; Ling, Hui; Ang, Xiaohui; Reddy, Shridhivya A.; Lee, Stephanie S-H.; Yang, Hong; Tan, Sock-Hoon [Department of Pharmacy, Faculty of Science, National University of Singapore (Singapore); Hayes, John D. [Jacqui Wood Cancer Centre, Division of Cancer Research, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland (United Kingdom); Chui, Wai-Keung [Department of Pharmacy, Faculty of Science, National University of Singapore (Singapore); Chew, Eng-Hui, E-mail: phaceh@nus.edu.sg [Department of Pharmacy, Faculty of Science, National University of Singapore (Singapore)

2013-11-01

Natural compounds containing vanilloid and Michael acceptor moieties appear to possess anti-cancer and chemopreventive properties. The ginger constituent shogaol represents one such compound. In this study, the anti-cancer potential of a synthetic novel shogaol analog 3-phenyl-3-shogaol (3-Ph-3-SG) was assessed by evaluating its effects on signaling pathways. At non-toxic concentrations, 3-Ph-3-SG suppressed cancer cell invasion in MDA-MB-231 and MCF-7 breast carcinoma cells through inhibition of PMA-activated MMP-9 expression. At similar concentrations, 3-Ph-3-SG reduced expression of the inflammatory mediators nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and prostanglandin-E{sub 2} (PGE{sub 2}) in RAW 264.7 macrophage-like cells. Inhibition of cancer cell invasion and inflammation by 3-Ph-3-SG were mediated through suppression of the nuclear factor-kappaB (NF-κB) signaling pathway. The 3-Ph-3-SG also demonstrated cytoprotective effects by inducing the antioxidant response element (ARE)-driven genes NAD(P)H quinone oxidoreductase-1 (NQO1) and heme oxygenase-1 (HO-1). Cytoprotection by 3-Ph-3-SG was achieved at least partly through modification of cysteine residues in the E3 ubiquitin ligase substrate adaptor Kelch-like ECH-associated protein 1 (Keap1), which resulted in accumulation of transcription factor NF-E2 p45-related factor 2 (Nrf2). The activities of 3-Ph-3-SG were comparable to those of 6-shogaol, the most abundant naturally-occurring shogaol, and stronger than those of 4-hydroxyl-null deshydroxy-3-phenyl-3-shogaol, which attested the importance of the 4-hydroxy substituent in the vanilloid moiety for bioactivity. In summary, 3-Ph-3-SG is shown to possess activities that modulate stress-associated pathways relevant to multiple steps in carcinogenesis. Therefore, it warrants further investigation of this compound as a promising candidate for use in chemotherapeutic and chemopreventive strategies. - Highlights: �

1-L-MT, an IDO inhibitor, prevented colitis-associated cancer by inducing CDC20 inhibition-mediated mitotic death of colon cancer cells.

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Liu, Xiuting; Zhou, Wei; Zhang, Xin; Ding, Yang; Du, Qianming; Hu, Rong

2018-04-01

Indoleamine 2,3-dioxygenase 1 (IDO1), known as IDO, catabolizes tryptophan through kynurenine pathway, whose activity is correlated with impaired clinical outcome of colorectal cancer. Here we showed that 1-L-MT, a canonical IDO inhibitor, suppressed proliferation of human colorectal cancer cells through inducing mitotic death. Our results showed that inhibition of IDO decreased the transcription of CDC20, which resulted in G2/M cycle arrest of HCT-116 and HT-29. Furthermore, 1-L-MT induced mitochondria injuries and caused apoptotic cancer cells. Importantly, 1-L-MT protected mice from azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon carcinogenesis, with reduced mortality, tumor number and size. What is more, IDO1-/- mice exhibited fewer tumor burdens and reduced proliferation in the neoplastic epithelium, while, 1-L-MT did not exhibit any further protective effects on IDO-/- mice, confirming the critical role of IDO and the protective effect of 1-L-MT-mediated IDO inhibition in CRC. Furthermore, 1-L-MT also alleviated CRC in Rag1-/- mice, demonstrating the modulatory effects of IDO independent of its role in modulating adaptive immunity. Taken together, our findings validated that the anti-proliferation effect of 1-L-MT in vitro and the prevention of CRC in vivo were through IDO-induced cell cycle disaster of colon cancer cells. Our results identified 1-L-MT as a promising candidate for the chemoprevention of CRC. © 2018 UICC.

Chemopreventive and Anticancer Activities of Allium victorialis var. platyphyllum Extracts.

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Kim, Hyun-Jeong; Park, Min Jeong; Park, Hee-Juhn; Chung, Won-Yoon; Kim, Ki-Rim; Park, Kwang-Kyun

2014-09-01

Allium victorialis var. platyphyllum is an edible perennial herb and has been used as a vegetable or as a Korean traditional medicine. Allium species have received much attention owing to their diverse pharmacological properties, including antioxidative, anti-inflammatory, and anticancer activities. However, A. victorialis var. platyphyllum needs more study. The chemopreventive potential of A. victorialis var. platyphyllum methanol extracts was examined by measuring 12-O-tetra-decanoylphorbol 13-acetate (TPA)-induced superoxide anion production in the differentiated HL-60 cells, TPA-induced mouse ear edema, and Ames/Salmonella mutagenicity. The apoptosis-inducing capabilities of the extracts were evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, 4',6-diamidino-2-phenylindole staining, and the DNA fragmentation assay in human colon cancer HT-29 cells. Antimetastatic activities of the extracts were also investigated in an experimental mouse lung metastasis model. The methanol extracts of A. victorialis var. platyphyllum rhizome (AVP-R) and A. victorialis var. platyphyllum stem (AVP-S) dose-dependently inhibited the TPA-induced generation of superoxide anion in HL-60 cells and TPA-induced ear edema in mice, as well as 7,12-dimethylbenz[a]anthracene (DMBA) and tert-butyl hydroperoxide (t-BOOH) -induced bacterial mutagenesis. AVP-R and AVP-S reduced cell viability in a dose-related manner and induced apoptotic morphological changes and internucleosomal DNA fragmentation in HT-29 cells. In the experimental mouse lung metastasis model, the formation of tumor nodules in lung tissue was significantly inhibited by the treatment of the extracts. AVP-R and AVP-S possess antioxidative, anti-inflammatory, antimutagenic, proapoptotic, and antimetastatic activities. Therefore, these extracts can serve as a beneficial supplement for the prevention and treatment of cancer.

Cyclooxygenase-2 inhibitors in colorectal cancer prevention: point.

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Arber, Nadir

2008-08-01

The limited success of current treatments for most advanced common malignancies highlights the importance of cancer prevention. Clinical trials on cyclooxygenase (COX) inhibitor drugs showed the potential of chemoprevention as a strategy for reducing cancer incidence, although not without associated side effects. The attractiveness of these drugs partly stems from an ability to engage multiple mechanisms of action by their potential to influence multiple components of the carcinogenesis pathway, from initiation to progression. There are two isoforms of the COX enzymes. COX-1 is constitutively expressed in normal tissues and serves as a "housekeeper" of mucosal integrity, whereas COX-2 is an immediate early response gene that is highly inducible by neoplastic and inflammatory stimuli. COX-2 is significantly overexpressed in colorectal neoplasms, making it an attractive therapeutic target. The drug market has been revolutionized by the development of preparations targeted selectively against COX-2, and a proof of concept has been achieved. Chemoprevention of colorectal cancer is already possible with celecoxib, but it is still not the ultimate drug of choice especially because of the cardiovascular risk associated with COX-2 inhibitors. Better patient selection and more effective and safer drugs are needed. Celecoxib is probably best used in a subset of individuals at moderate to high colorectal cancer risk and low risk of cardiovascular disease.

Managing cancer risk and decision making after kidney transplantation.

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Webster, A C; Wong, G; Craig, J C; Chapman, J R

2008-11-01

Kidney transplant recipients are at higher risk of cancer at most sites, and cancer after transplantation causes considerable morbidity and mortality. To optimize long-term patient outcomes, clinicians balance the prospect of graft failure and dialysis, with competing risks of diabetes, cardiovascular and cerebrovascular disease and the risk of malignancy. In this paper we critically examine the assumptions underpinning primary prevention, immunization, chemoprevention and screening programs, and highlight considerations when applying evidence to the kidney transplant population, and suggest a clinical research agenda that aims to define a rational approach to managing posttransplant cancer risk.

Chemoprevention of esophageal adenocarcinoma in a rat model by ursodeoxycholic acid.

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Ojima, Eisuke; Fujimura, Takashi; Oyama, Katsunobu; Tsukada, Tomoya; Kinoshita, Jun; Miyashita, Tomoharu; Tajima, Hidehiro; Fushida, Sachio; Harada, Shin-ichi; Mukaisho, Ken-ichi; Hattori, Takanori; Ohta, Tetsuo

2015-08-01

Reflux of bile acid into the esophagus induces esophagitis, inflammation-stimulated hyperplasia, metaplasia such as Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC). Caudal-type homeobox 2 (Cdx2) via nuclear factor (NF)-κB induced by bile acid is an important factor in the development of BE and EAC. In colorectal cancer, experimental data suggest a chemopreventive effect of ursodeoxycholic acid (UDCA). We hypothesized that UDCA may protect against the esophageal inflammation-metaplasia-carcinoma sequence by decreasing the overall proportion of the toxic bile acids. Wistar male rats that underwent a duodenoesophageal reflux procedure were divided into two groups. One group was given commercial chow (control group), and the other was given experimental chow containing UDCA (UDCA group). The animals were killed at 40 weeks after surgery, and their bile and esophagus were examined. In the UDCA group, the esophagitis was milder and the incidence of BE was significantly lower (p acid, UDCA was markedly increased in the UDCA group compared with the control group (32.7 ± 11.4 vs. 0.82 ± 0.33 mmol/L, p acid was decreased (32.7 ± 4.05 vs. 60.9 ± 8.26 mmol/L, p acid composition.

Molecular epigenetics in the management of ovarian cancer: Are we investigating a rational clinical promise?

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Ha eNguyen

2014-04-01

Full Text Available Epigenetics is essentially a phenotypical change in gene expression without any alteration of the DNA sequence; the emergence of epigenetics in cancer research and mainstream oncology is fueling new hope. However, it is not yet known whether this knowledge will translate to improved clinical management of ovarian cancer. In this malignancy, women are still undergoing chemotherapy similar to what was approved in 1978, which to this day represents one of the biggest breakthroughs for treating ovarian cancer. While liquid tumors are benefitting from epigenetically-related therapies, solid tumors like ovarian cancer are not (yet?. Herein we will review the science of molecular epigenetics, especially DNA methylation, histone modifications and microRNA, but also include transcription factors since they, too, are important in ovarian cancer. Preclinical and clinical research on the role of epigenetic modifications is summarized as well. Sadly, ovarian cancer remains an idiopathic disease, for the most part, and there are many areas of patient management which could benefit from improved technology. This review will also highlight the evidence suggesting that epigenetics may have preclinical utility in pharmacology and clinical applications for prognosis and diagnosis. Lastly, drugs currently in clinical trials (i.e. histone deacetylase inhibitors are discussed along with the promise for epigenetics in the exploitation of chemoresistance. Whether epigenetics will ultimately be the answer to better management in ovarian cancer is currently unknown; what we have now is hope.

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

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Elias Gounaris

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

Tamoxifen for women at high risk of breast cancer

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Nazarali, Safia A; Narod, Steven A

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 ...

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

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

2014-01-01

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

Primary prevention of colorectal cancer: myth or reality?

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Crosara Teixeira, Marcela; Braghiroli, Maria Ignez; Sabbaga, Jorge; Hoff, Paulo M

2014-11-07

Colorectal cancer incidence has been rising strongly in parallel with economic development. In the past few decades, much has been learned about the lifestyle, dietary and medication risk factors for this malignancy. With respect to lifestyle, compelling evidence indicates that prevention of weight gain and maintenance of a reasonable level of physical activity can positively influence in lowering the risk. Although there is controversy about the role of specific nutritional factors, consideration of dietary pattern as a whole appears useful for formulating recommendations. Though quite often recommended, the role for many supplements, including omega-3, vitamin D, folate, and vitamin B6, remains unsettled. Only calcium and vitamin D supplementation appear to add a modest benefit, particularly in those with a low daily intake. With regard to chemoprevention, medications such as aspirin and nonsteroidal anti-inflammatory drugs, and postmenopausal hormonal replacement for women might be associated with substantial reductions in colorectal cancer risk, though their utility is affected by their side effect profile. However, the role of agents such as statins, bisphosphonates and antioxidants have yet to be determined. Ultimately, primary prevention strategies focusing on modifying environmental, lifestyle risk factors, and chemopreventive drugs are options that have already been tested, and may impact on colon cancer incidence.

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

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Cedar H A Boakye

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

Nutrition Frontiers - Summer 2016 | Division of Cancer Prevention

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Volume 7, Issue 3 The summer issue of Nutrition Frontiers showcases the combined effects of ursolic acid and resveratrol for skin cancer, the potential chemopreventive effects of the dietary supplement 4-MU, and a method to monitor a heterocyclic aromatic amine in dyed hair. Learn about our spotlight investigators, Drs. Michael Caligiuri and Jianhua Yu, and their research on

Nutrition Frontiers - Spring 2016 | Division of Cancer Prevention

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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. |

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

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Gerhauser, Clarissa

2008-10-01

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

The effectiveness of cyclooxygenase-2 inhibitors and evaluation of angiogenesis in the model of experimental colorectal cancer.

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Gungor, Hilal; Ilhan, Nevin; Eroksuz, Hatice

2018-06-01

Colorectal cancer (CRC) is an important cause of cancer-related deaths worldwide. Early diagnosis and treatment of CRCs are of importance for improving the survival. In the present study, we studied the effects of nonsteroidal anti-inflammatory drugs (NSAIDs)-induced chemopreventive effects on tumor development incidence and angiogenesis in experimental CRC rats. 1,2-Dimethylhydrazine dihydrochloride (DMH) was used as cancer-inducing agent and two NSAIDs (celecoxib and diclofenac) were given orally as chemopreventive agents. Histopathological and immuno histochemical evaluations were performed in colorectal tissue samples, whereas angiogenesis parameters were studied in blood samples. Histopathological examination showed that adenocarcinoma (62.5%), dysplastic changes (31.25%) and inflammattory changes (6.25%) were detected in DMH group, whereas no pathological change was observed in control rats. In treatment groups, there was marked decrease in adenocarcinoma rate (30% and 10%, respectively). A significant increase was detected in MMP-2, MMP-9 levels and MMP-2/TIMP-2 ratio in DMH group as compared with controls and treatment groups. In immunohistochemical evaluations, there was an increase in intensity and extent of staining of MMP-2 and MMP-9 in DMH group as compared to controls and treatment groups. The decrease in celecoxib group was more prominent. Overall, it was concluded that NSAIDs, particularly cyclooxygenase-2 (COX-2) inhibitors, might have a protective effect on CRC development and slow down progression of tumor in a DMH-induced experimental cancer model. One of the possible mechanisms in the chemoprevention of colon cancer seems to be inhibition of angiogenesis by diclofenac and celecoxib. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Chemopreventive properties of raisins originating from Greece in colon cancer cells.

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Kountouri, Aggeliki M; Gioxari, Aristea; Karvela, Evangelia; Kaliora, Andriana C; Karvelas, Michalis; Karathanos, Vaios T

2013-02-26

Colorectal cancer is one of the major causes of cancer-related mortality in humans in both developed and developing countries. Dietary patterns influence the risk of colon cancer development, while plant-derived foods have gained great interest, due to the high content of antioxidants. Corinthian raisins (Currants, CR) and Sultanas (S) (Vitis vinifera L., Vitaceae) are dried vine fruits produced in Greece with many culinary uses in both the Mediterranean and the Western nutrition. In the present study, we investigated the effects of CR and S on human colon cancer cells. Methanol extracts of CR and S were used at different concentrations. The total polyphenol content and anti-radical activity were measured by Folin-Ciocalteu and DPPH, respectively. Antioxidant, anti-inflammatory and anti-proliferative effects on HT29 cell culture were evaluated. All extracts exhibited DPPH˙ scavenging activity in a dose-dependent manner. Both products suppressed cell proliferation, while the levels of glutathione and cyclooxygenase 2 were significantly decreased. A significant reduction in IL-8 levels and NF-kappaB p65 activation was also observed. Both antioxidant and anti-inflammatory effects were dependent on the duration of exposure. Results indicate that the methanol extracts of CR and S exhibit anti-radical activity in vitro, as well as cancer preventive efficacy on colon cancer cells, with S having slightly higher activity. The beneficial properties of these unique dried grapes are attributed to their high content of phenolic compounds.

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

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Constanze Buhrmann

2016-03-01

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

Redox Regulation in Cancer: A Double-edged Sword with Therapeutic Potential

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Asha Acharya

2010-01-01

Full Text Available Oxidative stress, implicated in the etiology of cancer, results from an imbalance in the production of reactive oxygen species (ROS and cell’s own antioxidant defenses. ROS deregulate the redox homeostasis and promote tumor formation by initiating an aberrant induction of signaling networks that cause tumorigenesis. Ultraviolet (UV exposures, γ-radiation and other environmental carcinogens generate ROS in the cells, which can exert apoptosis in the tumors, thereby killing the malignant cells or induce the progression of the cancer growth by blocking cellular defense system. Cancer stem cells take the advantage of the aberrant redox system and spontaneously proliferate. Oxidative stress and gene-environment interactions play a significant role in the development of breast, prostate, pancreatic and colon cancer. Prolonged lifetime exposure to estrogen is associated with several kinds of DNA damage. Oxidative stress and estrogen receptor-associated proliferative changes are suggested to play important roles in estrogen-induced breast carcinogenesis. BRCA1, a tumor suppressor against hormone responsive cancers such as breast and prostate cancer, plays a significant role in inhibiting ROS and estrogen mediated DNA damage; thereby regulate the redox homeostasis of the cells. Several transcription factors and tumor suppressors are involved during stress response such as Nrf2, NFκB and BRCA1. A promising strategy for targeting redox status of the cells is to use readily available natural substances from vegetables, fruits, herbs and spices. Many of the phytochemicals have already been identified to have chemopreventive potential, capable of intervening in carcinogenesis.

Caffeic Acid Induces Apoptosis in Human Cervical Cancer Cells Through the Mitochondrial Pathway

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Wei-Chun Chang

2010-12-01

Conclusion: Caffeic acid induces apoptosis by inhibiting Bcl-2 activity, leading to release of cytochrome c and subsequent activation of caspase-3, indicating that caffeic acid induces apoptosis via the mitochondrial apoptotic pathway. This also suggests that caffeic acid has a strong anti-tumor effect and may be a promising chemopreventive or chemotherapeutic agent.

Promising new developments in cancer chemotherapy.

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Ferrante, K; Winograd, B; Canetta, R

1999-01-01

The positive impact on survival of traditional chemotherapeutic agents has renewed interest in developing newer cytotoxic agents and orally active compounds with improved therapeutic indices. In addition, new insights into the pathways of human tumorigenesis have led to novel approaches aimed at specific mechanism-based targets. The taxane class, of which paclitaxel was the first member, has the unique ability to promote and stabilize microtubule function directly, thereby inhibiting mitotic progression and inducing apoptotic cell death. Paclitaxel provides treatment benefit in a broad range of solid tumors including breast, ovarian, and lung cancer. The success with paclitaxel stimulated interest in the microtubule as a new therapeutic target. Taxane analogues with improved preclinical efficacy have been identified and are entering clinical trials. The enthusiasm for oral anticancer agents and the therapeutic importance of platinum compounds has led to the development of JM216 (satraplatin), a novel platinum IV coordination complex with oral activity in cisplatin-resistant cell lines, which is now in phase III trials in prostate cancer. Another compound in late development is DPPE, a chemopotentiator that enhances the in vivo antitumor effects of cytotoxic agents such as doxorubicin, cyclophosphamide, and cisplatin. Agents that inhibit topoisomerase I and II have also been of interest. TAS-103 is a dual topoisomerase I and II inhibitor with preclinical efficacy in a broad spectrum of tumors and in multidrug-resistant tumor cell lines. Vaccination strategies represent a rational therapeutic approach in the minimal residual disease or high-risk adjuvant therapy setting. The GMK and MGV vaccines utilizing ganglioside antigens overexpressed on human tumors such as melanoma and small cell lung cancer appear to induce antibody production reliably at tolerable doses and are under further clinical investigation. Inhibition of matrix metalloproteinases (MMPs) is another

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

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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.

Carcinogenicity of chromium and chemoprevention: a brief update

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Wang Y

2017-08-01

Full Text Available Yafei Wang,1,* Hong Su,1,* Yuanliang Gu,1 Xin Song,1 Jinshun Zhao1,2 1Department of Preventative Medicine, Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, People’s Republic of China; 2Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, USA *These authors contributed equally to this work Abstract: Chromium has two main valence states: hexavalent chromium (Cr[VI] and trivalent chromium (Cr[III]. Cr(VI, a well-established human carcinogen, can enter cells by way of a sulfate/phosphate anion-transport system, and then be reduced to lower-valence intermediates consisting of pentavalent chromium (Cr[V], tetravalent chromium (Cr[IV] or Cr(III via cellular reductants. These intermediates may directly or indirectly result in DNA damage or DNA–protein cross-links. Although Cr(III complexes cannot pass easily through cell membranes, they have the ability to accumulate around cells to induce cell-surface morphological alteration and result in cell-membrane lipid injuries via disruption of cellular functions and integrity, and finally to cause DNA damage. In recent years, more research, including in vitro, in vivo, and epidemiological studies, has been conducted to evaluate the genotoxicity/carcinogenicity induced by Cr(VI and/or Cr(III compounds. At the same time, various therapeutic agents, especially antioxidants, have been explored through in vitro and in vivo studies for preventing chromium-induced genotoxicity/carcinogenesis. This review aims to provide a brief update on the carcinogenicity of Cr(VI and Cr(III and chemoprevention with different antioxidants. Keywords: hexavalent chromium, Cr(VI, trivalent chromium, Cr(III, genotoxicity, carcinogenicity, chemoprevention, antioxidant 

Effect of Chemical Prevention Drugs-based MicroRNAs and Their Target Genes 
on Tumor Inhibition

Directory of Open Access Journals (Sweden)

Yanhui JIANG

2015-04-01

Full Text Available Chemopreventive drugs including natural chemopreventive drugs and synthetic chemopreventive drugs, it not only can prevent cancer, can also play a role in tumor treatment. MicroRNAs (miRNAs is a kind of short chains of non-coding RNA, regulating the expression of many genes through the way of degradation of mRNA or inhibitting mRNA translation. In recent years, more and more studies have shown that chemopreventive drugs through influence the expression of miRNAs and their target genes play a role in the prevention and treatment in a variety of tumors, and chemopreventive drugs on the experimental study of miRNAs and their target genes in tumor have demonstrated a good safety and efficacy. Effect on chemopreventive drugs-based microRNAs and their target genes into cancer cells will be expected as a new starting point for cancer research. The thesis expounds and analyzes between the natural chemopreventive drugs and synthetic chemopreventive drugs and miRNAs and their target genes in tumor research progress.

Androgen Receptor Signaling in Bladder Cancer

Science.gov (United States)

Li, Peng; Chen, Jinbo; Miyamoto, Hiroshi

2017-01-01

Emerging preclinical findings have indicated that steroid hormone receptor signaling plays an important role in bladder cancer outgrowth. In particular, androgen-mediated androgen receptor signals have been shown to correlate with the promotion of tumor development and progression, which may clearly explain some sex-specific differences in bladder cancer. This review summarizes and discusses the available data, suggesting the involvement of androgens and/or the androgen receptor pathways in urothelial carcinogenesis as well as tumor growth. While the precise mechanisms of the functions of the androgen receptor in urothelial cells remain far from being fully understood, current evidence may offer chemopreventive or therapeutic options, using androgen deprivation therapy, in patients with bladder cancer. PMID:28241422

Androgen Receptor Signaling in Bladder Cancer

Directory of Open Access Journals (Sweden)

Peng Li

2017-02-01

Full Text Available Emerging preclinical findings have indicated that steroid hormone receptor signaling plays an important role in bladder cancer outgrowth. In particular, androgen-mediated androgen receptor signals have been shown to correlate with the promotion of tumor development and progression, which may clearly explain some sex-specific differences in bladder cancer. This review summarizes and discusses the available data, suggesting the involvement of androgens and/or the androgen receptor pathways in urothelial carcinogenesis as well as tumor growth. While the precise mechanisms of the functions of the androgen receptor in urothelial cells remain far from being fully understood, current evidence may offer chemopreventive or therapeutic options, using androgen deprivation therapy, in patients with bladder cancer.

The protective role of carotenoids and polyphenols in patients with head and neck cancer

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Hui-Ping Chang

2015-02-01

Full Text Available Head and neck cancer is a critical global health problem and approximately 650,000 patients per year are diagnosed with this type of cancer. In addition, head and neck cancer exhibits a high recurrence rate, readily causing second primary cancers in other locations, often yielding a poor prognosis. Current medical and surgical treatment options result in considerable impairment of speaking and swallowing functions, with side effects such as nausea, vomiting, bone marrow suppression, and renal damage, thereby impairing patients' quality of life. Thus, developing a prevention and therapeutic intervention strategy for head and neck cancer is vital. Phytochemicals have been shown to have a unique ability to protect cells from damage and modulation of cell repair. The chemopreventive activities of phytochemicals have also been demonstrated to be associated with their antioxidant properties and the induction and stimulation of intercellular communication via gap junctions, which play a role in the regulation of cancer cell cycle, differentiation, apoptosis, and stagnate cancer cell growth. Phytochemicals can also regulate cancer cell signaling pathways, reduce the invasion and metastasis of cancer cells, and protect normal cells during treatment, thus reducing the damage caused by chemotherapy and radiotherapy. The most studied of the chemopreventive effects of phytochemicals are the carotenoids and phenolics. In this review, we investigated the multiple mechanisms of carotenoids and polyphenols (PPs for use in preventing head and neck cancer, reducing the side effects of chemotherapy and radiotherapy, improving patient survival rates, and reducing the occurrence rate of second primary cancers.

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

Czech Academy of Sciences Publication Activity Database

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

2016-01-01

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

Melanoma Vaccines: Mixed Past, Promising Future

Science.gov (United States)

Ozao-Choy, Junko; Lee, Delphine J.; Faries, Mark B.

2014-01-01

Synopsis Cancer vaccines were one of the earliest forms of immunotherapy to be investigated. Past attempts to vaccinate against cancer, including melanoma, have mixed results, revealing the complexity of what was thought to be a simple concept. However, several recent successes and the combination of improved knowledge of tumor immunology and the advent of new immunomodulators make vaccination a promising strategy for the future. PMID:25245965

Nanoencapsulation of polyphenols for protective effect against colon-rectal cancer.

Science.gov (United States)

Santos, Isis S; Ponte, Bruno M; Boonme, Prapaporn; Silva, Amélia M; Souto, Eliana B

2013-01-01

The human population at large is exposed to many critical factors (e.g. bad food habits, chemical substances, and stress) leading to the development of serious diseases. Colon or colorectal cancer is one of the most prevalent types of cancer in many countries. Despite being a multi-factorial chronic disease, resulting from the interaction of multiple genetic and environmental factors, the critical factor is mostly a poor diet regimen. Therefore, an accumulation of constant mutations leads to a complex arrangement of events during tumor initiation, development and propagation. It is well known that many plants are rich in polyphenols with anti-oxidant, anti-atherogenic, anti-diabetic, anti-cancer, anti-viral, and anti-inflammatory properties. These compounds are secondary metabolites with the ability to donate electrons to free radicals through different mechanisms. In recent years, a large number of studies have attributed a protective effect to polyphenols and foods containing these compounds (e.g. plants, vegetables, cereals, tea, coffee or chocolate). Polyphenolic compounds have been described to inhibit cancer development and propagation, being used as chemopreventive agents. Some polyphenols reported a preventive action against colon cancer, e.g. curcumin, gallic acid, ellagic acid, and epigallocatechin-3-gallate. The present article focuses on the properties of these molecules as chemopreventive agents and the recent advances on their formulation in nanoparticulate systems for targeted therapy and increased bioavailability. Copyright © 2012 Elsevier Inc. All rights reserved.

The role of nutraceuticals in the regulation of Wnt and Hedgehog signaling in cancer

Science.gov (United States)

Li, Yiwei; Wang, Zhiwei; Kong, Dejuan

2010-01-01

Multiple cellular signaling pathways have been involved in the processes of cancer cell invasion and metastasis. Among many signaling pathways, Wnt and Hedgehog (Hh) signaling pathways are critically involved in embryonic development, in the biology of cancer stem cells (CSCs) and in the acquisition of epithelial to mesenchymal transition (EMT), and thus this article will remain focused on Wnt and Hh signaling. Since CSCs and EMT are also known to be responsible for cancer cell invasion and metastasis, the Wnt and Hedgehog signaling pathways are also intimately associated with cancer invasion and metastasis. Emerging evidence suggests the beneficial role of chemopreventive agents commonly known as nutraceutical in cancer. Among many such agents, soy isoflavones, curcumin, green tea polyphenols, 3,3′-diindolylmethane, resveratrol, lycopene, vitamin D, etc. have been found to prevent, reverse, or delay the carcinogenic process. Interestingly, these agents have also shown to prevent or delay the progression of cancer, which could in part be due to their ability to attack CSCs or EMT-type cells by attenuating the Wnt and Hedgehog signaling pathways. In this review, we summarize the current state of our knowledge on the role of Wnt and Hedgehog signaling pathways, and their targeted inactivation by chemopreventive agents (nutraceuticals) for the prevention of tumor progression and/or treatment of human malignancies. PMID:20711635

Promising approaches to circumvent the blood-brain barrier: progress, pitfalls and clinical prospects in brain cancer.

Science.gov (United States)

Papademetriou, Iason T; Porter, Tyrone

2015-01-01

Brain drug delivery is a major challenge for therapy of central nervous system (CNS) diseases. Biochemical modifications of drugs or drug nanocarriers, methods of local delivery, and blood-brain barrier (BBB) disruption with focused ultrasound and microbubbles are promising approaches which enhance transport or bypass the BBB. These approaches are discussed in the context of brain cancer as an example in CNS drug development. Targeting to receptors enabling transport across the BBB offers noninvasive delivery of small molecule and biological cancer therapeutics. Local delivery methods enable high dose delivery while avoiding systemic exposure. BBB disruption with focused ultrasound and microbubbles offers local and noninvasive treatment. Clinical trials show the prospects of these technologies and point to challenges for the future.

Curcumin as a multifaceted compound against human papilloma virus infection and cervical cancers: A review of chemistry, cellular, molecular, and preclinical features.

Science.gov (United States)

Teymouri, Manouchehr; Pirro, Matteo; Johnston, Thomas P; Sahebkar, Amirhosein

2017-05-06

Curcumin, the bioactive polyphenolic ingredient of turmeric, has been extensively studied for its effects on human papilloma virus (HPV) infection as well as primary and malignant squamous cervical cancers. HPV infections, especially those related to HPV 16 and 18 types, have been established as the leading cause of cervical cancer; however, there are also additional contributory factors involved in the etiopathogenesis of cervical cancers. Curcumin has emerged as having promising chemopreventive and anticancer effects against both HPV-related and nonrelated cervical cancers. In this review, we first discuss the biological relevance of curcumin and both its pharmacological effects and pharmaceutical considerations from a chemical point of view. Next, the signaling pathways that are modulated by curcumin and are relevant to the elimination of HPV infection and treatment of cervical cancer are discussed. We also present counter arguments regarding the effects of curcumin on signaling pathways and molecular markers dysregulated by benzo(a)pyrene (Bap), a carcinogen found in pathological cervical lesions of women who smoke frequently, and estradiol, as two important risk factors involved in persistent HPV-infection and cervical cancer. Finally, various strategies to enhance the pharmacological activity and pharmacokinetic characteristics of curcumin are discussed with examples of studies in experimental models of cervical cancer. © 2016 BioFactors, 43(3):331-346, 2017. © 2016 International Union of Biochemistry and Molecular Biology.

Laser photobiomodulation: A new promising player for the multi-hallmark treatment of advanced cancer

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Luis Santana-Blank

2013-10-01

Full Text Available This article does not include an abstract. Full text of this article is available in PDF.Cite this article as:Santana-Blank L, Rodríguez-Santana E, Reyes H, Santana-Rodríguez J, Santana-Rodríguez K. Laser photobiomodulation: A new promising player for the multi-hallmark treatment of advanced cancer. Int J Cancer Ther Oncol 2013;1(1:01012. DOI: 10.14319/ijcto.0101.2-------------------------------------- Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman","serif";}

Breast cancer anxiety's associations with responses to a chemoprevention decision aid.

Science.gov (United States)

Dillard, Amanda J; Scherer, Laura; Ubel, Peter A; Smith, Dylan M; Zikmund-Fisher, Brian J; McClure, Jennifer B; Greene, Sarah; Stark, Azadeh; Fagerlin, Angela

2013-01-01

Few studies have examined how specific emotions may affect decision-making processes. Anxiety may be especially relevant in health decisions such as those related to cancer in which thoughts of illness or death may be abundant. We examined associations between women's anxiety about developing breast cancer and variables related to their decision to take a medication that could reduce their chances of the disease. Six-hundred and thirty-two American women, who had an increased risk of breast cancer, reviewed a web-based decision aid about tamoxifen. We examined associations between their baseline, self-reported anxiety about developing the disease and post decision aid measures including knowledge about tamoxifen, attitude toward the medication, and behavioral intentions to look for more information and take the medication. Results showed that anxiety was not associated with knowledge about tamoxifen, but it was associated with attitude toward the medication such that women who were more anxious about developing breast cancer were more likely to think the benefits were worth the risks. Greater anxiety was also associated with greater behavioral intentions to look for additional information and take the medication in the next few months. Secondary analyses showed that behavioral intentions were related to knowledge of tamoxifen and attitude toward the medication only for women who were reporting low levels of anxiety. Overall, the findings suggest that anxiety about breast cancer may motivate interest in tamoxifen and not necessarily through affecting knowledge or attitudes. Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemopreventive glucosinolate accumulation in various broccoli and collard tissues: Microfluidic-based targeted transcriptomics for by-product valorization.

Science.gov (United States)

Lee, Young-Sang; Ku, Kang-Mo; Becker, Talon M; Juvik, John A

2017-01-01

Floret, leaf, and root tissues were harvested from broccoli and collard cultivars and extracted to determine their glucosinolate and hydrolysis product profiles using high performance liquid chromatography and gas chromotography. Quinone reductase inducing bioactivity, an estimate of anti-cancer chemopreventive potential, of the extracts was measured using a hepa1c1c7 murine cell line. Extracts from root tissues were significantly different from other tissues and contained high levels of gluconasturtiin and glucoerucin. Targeted gene expression analysis on glucosinolate biosynthesis revealed that broccoli root tissue has elevated gene expression of AOP2 and low expression of FMOGS-OX homologs, essentially the opposite of what was observed in broccoli florets, which accumulated high levels of glucoraphanin. Broccoli floret tissue has significantly higher nitrile formation (%) and epithionitrile specifier protein gene expression than other tissues. This study provides basic information of the glucosinolate metabolome and transcriptome for various tissues of Brassica oleracea that maybe utilized as potential byproducts for the nutraceutical market.

Promising approaches to circumvent the blood-brain barrier: progress, pitfalls and clinical prospects in brain cancer

OpenAIRE

Papademetriou, Iason T; Porter, Tyrone

2015-01-01

Brain drug delivery is a major challenge for therapy of central nervous system (CNS) diseases. Biochemical modifications of drugs or drug nanocarriers, methods of local delivery, and blood–brain barrier (BBB) disruption with focused ultrasound and microbubbles are promising approaches which enhance transport or bypass the BBB. These approaches are discussed in the context of brain cancer as an example in CNS drug development. Targeting to receptors enabling transport across the BBB offers non...

A Chemopreventive Trial to Study the Effects of High Tea Consumption on Smoking-Related Oxidative Stress

National Research Council Canada - National Science Library

Hakim, Iman

2004-01-01

.... We are conducting a 6-month randomized, controlled, double-blinded chemopreventive trial in a group of COPD subjects who are being randomized to green or black tea preparations or a control intervention (matching placebo...

A Chemopreventive Trial to Study the Effects of High Tea Consumption on Smoking-Related Oxidative Stress

National Research Council Canada - National Science Library

Hakim, Iman A

2006-01-01

.... We are conducting a 6-month randomized, controlled, double-blinded chemopreventive trial in a group of COPD subjects who are being randomized to green or black tea preparations or a control intervention (matching placebo...

A Chemoprevention Trial to Study the Effects of High Tea Consumption on Smoking-Related Oxidative Stress

National Research Council Canada - National Science Library

Hakim, Iman A

2005-01-01

.... We are conducting a 6-month randomized, controlled, double-blinded chemopreventive trial in a group of COPD subjects who are being randomized to green or black tea preparations or a control intervention (matching placebo...

A Chemoprevention Trial to Study the Effects of High Tea Consumption on Smoking-Related Oxidative Stress

National Research Council Canada - National Science Library

Hakim, Iman A

2008-01-01

.... We are conducting a 6-month randomized controlled double-blinded chemopreventive trial in a group of COPD subjects who are being randomized to green or black tea preparations or a control intervention (matching placebo...

Aqueous Cinnamon Extract (ACE-c) from the bark of Cinnamomum cassia causes apoptosis in human cervical cancer cell line (SiHa) through loss of mitochondrial membrane potential

International Nuclear Information System (INIS)

Koppikar, Soumya J; Choudhari, Amit S; Suryavanshi, Snehal A; Kumari, Shweta; Chattopadhyay, Samit; Kaul-Ghanekar, Ruchika

2010-01-01

Chemoprevention, which includes the use of synthetic or natural agents (alone or in combination) to block the development of cancer in human beings, is an extremely promising strategy for cancer prevention. Cinnamon is one of the most widely used herbal medicines with diverse biological activities including anti-tumor activity. In the present study, we have reported the anti-neoplastic activity of cinnamon in cervical cancer cell line, SiHa. The aqueous cinnamon extract (ACE-c) was analyzed for its cinnamaldehyde content by HPTLC analysis. The polyphenol content of ACE-c was measured by Folin-Ciocalteau method. Cytotoxicity analysis was performed by MTT assay. We studied the effect of cinnamon on growth kinetics by performing growth curve, colony formation and soft agar assays. The cells treated with ACE-c were analyzed for wound healing assay as well as for matrix metalloproteinase-2 (MMP-2) expression at mRNA and protein level by RT-PCR and zymography, respectively. Her-2 protein expression was analyzed in the control and ACE-c treated samples by immunoblotting as well as confocal microscopy. Apoptosis studies and calcium signaling assays were analyzed by FACS. Loss of mitochondrial membrane potential (Δψ m ) in cinnamon treated cells was studied by JC-1 staining and analyzed by confocal microscopy as well as FACS. Cinnamon alters the growth kinetics of SiHa cells in a dose-dependent manner. Cells treated with ACE-c exhibited reduced number of colonies compared to the control cells. The treated cells exhibited reduced migration potential that could be explained due to downregulation of MMP-2 expression. Interestingly, the expression of Her-2 oncoprotein was significantly reduced in the presence of ACE-c. Cinnamon extract induced apoptosis in the cervical cancer cells through increase in intracellular calcium signaling as well as loss of mitochondrial membrane potential. Cinnamon could be used as a potent chemopreventive drug in cervical cancer

Aqueous Cinnamon Extract (ACE-c from the bark of Cinnamomum cassia causes apoptosis in human cervical cancer cell line (SiHa through loss of mitochondrial membrane potential

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Chattopadhyay Samit

2010-05-01

Full Text Available Abstract Background Chemoprevention, which includes the use of synthetic or natural agents (alone or in combination to block the development of cancer in human beings, is an extremely promising strategy for cancer prevention. Cinnamon is one of the most widely used herbal medicines with diverse biological activities including anti-tumor activity. In the present study, we have reported the anti-neoplastic activity of cinnamon in cervical cancer cell line, SiHa. Methods The aqueous cinnamon extract (ACE-c was analyzed for its cinnamaldehyde content by HPTLC analysis. The polyphenol content of ACE-c was measured by Folin-Ciocalteau method. Cytotoxicity analysis was performed by MTT assay. We studied the effect of cinnamon on growth kinetics by performing growth curve, colony formation and soft agar assays. The cells treated with ACE-c were analyzed for wound healing assay as well as for matrix metalloproteinase-2 (MMP-2 expression at mRNA and protein level by RT-PCR and zymography, respectively. Her-2 protein expression was analyzed in the control and ACE-c treated samples by immunoblotting as well as confocal microscopy. Apoptosis studies and calcium signaling assays were analyzed by FACS. Loss of mitochondrial membrane potential (Δψm in cinnamon treated cells was studied by JC-1 staining and analyzed by confocal microscopy as well as FACS. Results Cinnamon alters the growth kinetics of SiHa cells in a dose-dependent manner. Cells treated with ACE-c exhibited reduced number of colonies compared to the control cells. The treated cells exhibited reduced migration potential that could be explained due to downregulation of MMP-2 expression. Interestingly, the expression of Her-2 oncoprotein was significantly reduced in the presence of ACE-c. Cinnamon extract induced apoptosis in the cervical cancer cells through increase in intracellular calcium signaling as well as loss of mitochondrial membrane potential. Conclusion Cinnamon could be used as a

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

International Nuclear Information System (INIS)

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

2015-01-01

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

Potential applications of curcumin and its novel synthetic analogs and nanotechnology-based formulations in cancer prevention and therapy

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Batra Surinder K

2011-08-01

Full Text Available Abstract Curcumin has attracted great attention in the therapeutic arsenal in clinical oncology due to its chemopreventive, antitumoral, radiosensibilizing and chemosensibilizing activities against various types of aggressive and recurrent cancers. These malignancies include leukemias, lymphomas, multiple myeloma, brain cancer, melanoma and skin, lung, prostate, breast, ovarian, liver, gastrointestinal, pancreatic and colorectal epithelial cancers. Curcumin mediates its anti-proliferative, anti-invasive and apoptotic effects on cancer cells, including cancer stem/progenitor cells and their progenies, through multiple molecular mechanisms. The oncogenic pathways inhibited by curcumin encompass the members of epidermal growth factor receptors (EGFR and erbB2, sonic hedgehog (SHH/GLIs and Wnt/β-catenin and downstream signaling elements such as Akt, nuclear factor-kappa B (NF-κB and signal transducers and activators of transcription (STATs. In counterbalance, the high metabolic instability and poor systemic bioavailability of curcumin limit its therapeutic efficacy in human. Of great therapeutic interest, the selective delivery of synthetic analogs or nanotechnology-based formulations of curcumin to tumors, alone or in combination with other anticancer drugs, may improve their chemopreventive and chemotherapeutic efficacies against cancer progression and relapse. Novel curcumin formulations may also be used to reverse drug resistance, eradicate the total cancer cell mass and improve the anticarcinogenic efficacy of the current anti-hormonal and chemotherapeutic treatments for patients with various aggressive and lethal cancers.

Reverse screening methods to search for the protein targets of chemopreventive compounds

Science.gov (United States)

Huang, Hongbin; Zhang, Guigui; Zhou, Yuquan; Lin, Chenru; Chen, Suling; Lin, Yutong; Mai, Shangkang; Huang, Zunnan

2018-05-01

This article is a systematic review of reverse screening methods used to search for the protein targets of chemopreventive compounds or drugs. Typical chemopreventive compounds include components of traditional Chinese medicine, natural compounds and Food and Drug Administration (FDA)-approved drugs. Such compounds are somewhat selective but are predisposed to bind multiple protein targets distributed throughout diverse signaling pathways in human cells. In contrast to conventional virtual screening, which identifies the ligands of a targeted protein from a compound database, reverse screening is used to identify the potential targets or unintended targets of a given compound from a large number of receptors by examining their known ligands or crystal structures. This method, also known as in silico or computational target fishing, is highly valuable for discovering the target receptors of query molecules from terrestrial or marine natural products, exploring the molecular mechanisms of chemopreventive compounds, finding alternative indications of existing drugs by drug repositioning, and detecting adverse drug reactions and drug toxicity. Reverse screening can be divided into three major groups: shape screening, pharmacophore screening and reverse docking. Several large software packages, such as Schrödinger and Discovery Studio; typical software/network services such as ChemMapper, PharmMapper, idTarget and INVDOCK; and practical databases of known target ligands and receptor crystal structures, such as ChEMBL, BindingDB and the Protein Data Bank (PDB), are available for use in these computational methods. Different programs, online services and databases have different applications and constraints. Here, we conducted a systematic analysis and multilevel classification of the computational programs, online services and compound libraries available for shape screening, pharmacophore screening and reverse docking to enable non-specialist users to quickly learn and

The neem limonoids azadirachtin and nimbolide inhibit hamster cheek pouch carcinogenesis by modulating xenobiotic-metabolizing enzymes, DNA damage, antioxidants, invasion and angiogenesis.

Science.gov (United States)

Priyadarsini, Ramamurthi Vidya; Manikandan, Palrasu; Kumar, Gurram Harish; Nagini, Siddavaram

2009-05-01

The neem tree has attracted considerable research attention as a rich source of limonoids that have potent antioxidant and anti-cancer properties. The present study was designed to evaluate the chemopreventive potential of the neem limonoids azadirachtin and nimbolide based on in vitro antioxidant assays and in vivo inhibitory effects on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. Both azadirachtin and nimbolide exhibited concentration-dependent anti-radical scavenging activity and reductive potential in the order: nimbolide > azadirachtin > ascorbate. Administration of both azadirachtin and nimbolide inhibited the development of DMBA-induced HBP carcinomas by influencing multiple mechanisms including prevention of procarcinogen activation and oxidative DNA damage, upregulation of antioxidant and carcinogen detoxification enzymes and inhibition of tumour invasion and angiogenesis. On a comparative basis, nimbolide was found to be a more potent antioxidant and chemopreventive agent and offers promise as a candidate agent in multitargeted prevention and treatment of cancer.

Bio-guided fractionation of methanol extract of Ziziphus mauritiana Lam. (bark and effect of the most active fraction on cancer cell lines

Directory of Open Access Journals (Sweden)

Richard Simo Tagne

2015-04-01

Full Text Available Objective: To investigate the anticancer and antioxidant potential of methanol bark extract of Ziziphus mauritiana (Z. mauritiana, which is used by traditional healers to cure some cases of cancer in Cameroon. Methods: The methanol crude extract of Z. mauritiana has the antiproliferative activity on four cancer cell lines and its antioxidant activity. The extract was partitioned in five different solvents, and each fraction was tested. The effect of the most antiproliferative fraction on cell cycle was determined. Bio-guided fractionation was performed on the fraction with the highest antiproliferative and the highest antioxidant activities. Results: Z. mauritiana methanol extract was active on all tested cells, and showed promising antioxidant activity. All fractions except hexane fraction were active with the dichloromethane fraction being the most active and showed S and G2-M phase arrest (P<0.01 on cell cycle progression of NCI-H460 and MCF-7, respectively. Bio-guided fractionation of the dichloromethane fraction led to lupeol and betulinic acid. The greatest antioxidant activity was recorded with ethyl acetate fraction and its fractionation led to catechin and epigallocatechin. Conclusions: Overall, this study showed that Z. mauritiana barks has benefits as a chemoprevention agent cancer.

Both phenolic and non-phenolic green tea fractions inhibit migration of cancer cells

Science.gov (United States)

Green tea consumption is associated with chemoprevention of many cancer types. Fresh tea leaves are rich in polyphenolic catechins, which can constitute up to 30% of the dry leaf weight. While the polyphenols of green tea have been well investigated, it is still largely unknown, whether or not non-p...

Natural ways to prevent and treat oral cancer

Directory of Open Access Journals (Sweden)

Shweta Danaraddi

2014-01-01

Full Text Available Oral cancer is one of the usual causes of mortality all over the world, with a five-year survival rate of only 50%. Oral cancers are treated primarily by surgery with / without adjuvant radiotherapy and / or chemotherapy. However, there is significant post-treatment morbidity and mortality secondary to recurrences. Dietary supplements like fruits and vegetables are rich in phytochemicals and provide a variety of antioxidants like vitamin A, C, E. Spirulina, Selenium, Green tea (EGCG, Neem, Tomatoes (lycopene, Turmeric (curcumin, and some medicinal mushrooms are also used as chemopreventive and chemotherapeutic agents. This overview emphasizes on natural therapies to fight against oral cancer. Thus, there are several natural compounds that can enhance the prevention of oral cancer.

Effects and Costs of Breast Cancer screening in women with a familial or genetic predisposition

NARCIS (Netherlands)

A.J. Rijnsburger (Rian)

2005-01-01

textabstract"Women with a BRCA1 or BRCA2 mutation, who have a considerable increased risk of developing breast cancer, now face the choice of intensive screening, prophylactic surgery or chemoprevention. The efficacy of the various medical options and the durability of its effects are of major

Emerging therapeutic potential of graviola and its constituents in cancers.

Science.gov (United States)

Qazi, Asif Khurshid; Siddiqui, Jawed A; Jahan, Rahat; Chaudhary, Sanjib; Walker, Larry A; Sayed, Zafar; Jones, Dwight T; Batra, Surinder K; Macha, Muzafar A

2018-04-05

Cancer remains a leading cause of death in the USA and around the world. Although the current synthetic inhibitors used in targeted therapies have improved patient prognosis, toxicity and development of resistance to these agents remain a challenge. Plant-derived natural products and their derivatives have historically been used to treat various diseases, including cancer. Several leading chemotherapeutic agents are directly or indirectly based on botanical natural products. Beyond these important drugs, however, a number of crude herbal or botanical preparations have also shown promising utility for cancer and other disorders. One such natural resource is derived from certain plants of the family Annonaceae, which are widely distributed in tropical and subtropical regions. Among the best known of these is Annona muricata, also known as soursop, graviola or guanabana. Extracts from the fruit, bark, seeds, roots and leaves of graviola, along with several other Annonaceous species, have been extensively investigated for anticancer, anti-inflammatory and antioxidant properties. Phytochemical studies have identified the acetogenins, a class of bioactive polyketide-derived constituents, from the extracts of Annonaceous species, and dozens of these compounds are present in different parts of graviola. This review summarizes current literature on the therapeutic potential and molecular mechanism of these constituents from A.muricata against cancer and many non-malignant diseases. Based on available data, there is good evidence that these long-used plants could have both chemopreventive and therapeutic potential. Appropriate attention to safety studies will be important to assess their effectiveness on various diseases caused or promoted by inflammation.

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.

Upregulation of intrinsic apoptotic pathway in NSAIDs mediated chemoprevention of experimental lung carcinogenesis.

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Setia, Shruti; Sanyal, Sankar N

2012-01-01

Non-steroidal anti-inflammatory drugs (NSAIDs) act by inhibition of cyclooxygenase-2 (COX-2), which is overexpressed in cancer. The role of COX-2 and apoptosis were evaluated in 9,10-dimethylbenz(a)anthracene (DMBA)-induced lung cancer in rat and chemoprevention with indomethacin, a traditional NSAID and etoricoxib, a selective COX-2 inhibitor. The animals were divided into Control, DMBA, DMBA+ indomethacin and DMBA+ etoricoxib groups. They received a single intratracheal instillation of DMBA while NSAIDs were given orally daily for 32 weeks. Besides morphology and histology of lungs, RT-PCR, western blots and immunohistochemistry were performed for the expression of apoptotic proteins and COX enzymes. Apoptosis was studied by DNA fragmentation and fluorescent staining. The occurrence of tumors and lesions was noted in the DMBA animals, besides constricted alveolar spaces and hyperplasia. COX-1 was found to be uniformly expressed while COX-2 level was raised significantly in DMBA group. The apoptotic proteins, apaf-1, caspase-9 and caspase-3 were highly diminished in DMBA group but restored to normal level in NSAIDs groups. Also, apoptosis was suppressed in carcinogen group by DNA fragmentation analysis and fluorescent staining of the lung cells while co-administration of NSAIDs along with DMBA led to the restoration of apoptosis. DMBA administration to the rats led to tumorigenesis in the lungs, had no effects on COX-1 expression, while elevating the COX-2 levels and suppressing apoptosis. The treatment with NSAIDs led to the amelioration of these effects. However, etoricoxib which is a COX-2 specific inhibitor, was found to be more effective than the traditional NSAID, indomethacin.

Lycopene Protects Against Spontaneous Ovarian Cancer Formation in Laying Hens.

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Sahin, Kazim; Yenice, Engin; Tuzcu, Mehmet; Orhan, Cemal; Mizrak, Cengizhan; Ozercan, Ibrahim H; Sahin, Nurhan; Yilmaz, Bahiddin; Bilir, Birdal; Ozpolat, Bulent; Kucuk, Omer

2018-03-01

Dietary intake of lycopene has been associated with a reduced risk of ovarian cancer, suggesting its chemopreventive potential against ovarian carcinogenesis. Lycopene's molecular mechanisms of action in ovarian cancer have not been fully understood. Therefore, in the present study, we investigated the effects of lycopene on the ovarian cancer formation using the laying hen model, a biologically relevant animal model of spontaneous ovarian carcinogenesis due to high incidence rates similar to humans. In this study, a total of 150 laying hens at age of 102 weeks were randomized into groups of 50: a control group (0 mg of lycopene per kg of diet) and two treatment groups (200 mg or 400 mg of lycopene per kg of diet, or ~26 and 52 mg/d/hen, respectively). At the end of 12 months, blood, ovarian tissues and tumors were collected. We observed that lycopene supplementation significantly reduced the overall ovarian tumor incidence ( P Lycopene also significantly decreased the rate of adenocarcinoma, including serous and mucinous subtypes ( P lycopene-fed hens compared to control birds ( P lycopene reduced the expression of NF-κB while increasing the expression of nuclear factor erythroid 2 and its major target protein, heme oxygenase 1. In addition, lycopene supplementation decreased the expression of STAT3 by inducing the protein inhibitor of activated STAT3 expression in the ovarian tissues. Taken together, our findings strongly support the potential of lycopene in the chemoprevention of ovarian cancer through antioxidant and anti-inflammatory mechanisms.

Can transcriptomics provide insight into the underlying chemopreventive mechanisms of complex mixtures of phytochemicals in humans?

NARCIS (Netherlands)

Breda, van S.G.; Wilms, L.C.; Gaj, S.; Briedé, J.J.; Helsper, J.P.F.G.; Kleinjans, J.C.; Kok, de T.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

Chemopreventive effect of artesunate in 1,2-dimethylhydrazine-induced rat colon carcinogenesis

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Sazal Patyar

2017-01-01

Full Text Available Artesunate (ART is a semisynthetic derivative of artemisinin. Artemisinin and its derivatives have shown profound cytotoxicity and antitumor activity in addition to antimalarial activity in various studies. As the in vivo chemopreventive efficacy of ART in colon carcinogenesis has not been investigated so far, the aim of the current study was to study the chemopreventive effect of ART in 1,2-dimethylhydrazine (DMH-induced rat colon carcinogenesis. Animals were divided into four groups (n = 6: Group I - vehicle (1 mM ethylenediaminetetraacetic acid, Group II - DMH (20 mg/kg, Group III - DMH + 5-fluorouracil (81 mg/kg, Group IV - DMH + ART (6.7 mg/kg. After completion of 15 weeks of treatment, rats were sacrificed under ether anesthesia by cervical dislocation for assessment of lipid peroxidation (LPO, antioxidant status, average number of aberrant crypt foci (ACF, and cytokine levels. ART administration significantly decreased the average number of ACF/microscopic field. Similarly, LPO level was decreased and antioxidant activities were enhanced after ART treatment. ART decreased the levels of proinflammatory cytokines and induced apoptosis in the colons of DMH-treated rats. The results of this study suggest that ART has a beneficial effect against chemically induced colonic preneoplastic progression in rats.

Trial endpoints for drug approval in oncology: Chemoprevention.

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Beitz, J

2001-04-01

As with other drugs, new drug applications for marketing approval of chemopreventive drugs must include data from adequate and well-controlled clinical trials that demonstrate effectiveness and safety for the intended use. This article summarizes the regulatory requirements for traditional marketing approval, as well as for approval under the accelerated approval regulations. Unlike traditional approval, accelerated approval is based on a surrogate endpoint that is reasonably likely to predict clinical benefit. Discussions with the Food and Drug Administration (FDA) regarding the validity of trial endpoints that may serve as surrogates for clinical benefit for accelerated approval should take place as early as possible in drug development. Meetings with the FDA to discuss these issues may be requested throughout the clinical development of a new drug.

High-polyphenol sorghum bran extract inhibits cancer cell growth through DNA damage, cell cycle arrest, and apoptosis

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As diet is one of the major controllable factors in cancer development, potentially chemopreventive foods are of significant interest to public health. One such food is sorghum (Sorghum bicolor), a cereal grain that contains varying concentrations of polyphenols. In a panel of 15 sorghum germplasm...

Beta-endorphin Cell Therapy for Cancer Prevention

OpenAIRE

Zhang, Changqing; Murugan, Sengottuvelan; Boyadjieva, Nadka; Jabbar, Shaima; Shrivastava, Pallavi; Sarkar, Dipak K.

2014-01-01

Beta-endorphin (BEP) producing neuron in the hypothalamus plays a key role in brining the stress axis to a state of homeostasis and maintaining body immune defense system. Long-term delivery of BEP to obtain beneficial effect on chemoprevention is challenging, since the peptide rapidly develop tolerance. Using rats as animal model, we show here that transplantation of beta-endorphin neurons into the hypothalamus suppressed carcinogens- and hormone-induced cancers in various tissues and preven...

[6]-Gingerol induces caspase-dependent apoptosis and prevents PMA-induced proliferation in colon cancer cells by inhibiting MAPK/AP-1 signaling.

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E K Radhakrishnan

Full Text Available We report mechanism-based evidence for the anticancer and chemopreventive efficacy of [6]-gingerol, the major active principle of the medicinal plant, Ginger (Zingiber officinale, in colon cancer cells. The compound was evaluated in two human colon cancer cell lines for its cytotoxic effect and the most sensitive cell line, SW-480, was selected for the mechanistic evaluation of its anticancer and chemopreventive efficacy. The non-toxic nature of [6]-gingerol was confirmed by viability assays on rapidly dividing normal mouse colon cells. [6]-gingerol inhibited cell proliferation and induced apoptosis as evidenced by externalization of phosphatidyl serine in SW-480, while the normal colon cells were unaffected. Sensitivity to [6]-gingerol in SW-480 cells was associated with activation of caspases 8, 9, 3 &7 and cleavage of PARP, which attests induction of apoptotic cell death. Mechanistically, [6]-gingerol down-regulated Phorbol Myristate Acetate (PMA induced phosphorylation of ERK1/2 and JNK MAP kinases and activation of AP-1 transcription factor, but had only little effects on phosphorylation of p38 MAP kinase and activation of NF-kappa B. Additionally, it complemented the inhibitors of either ERK1/2 or JNK MAP kinase in bringing down the PMA-induced cell proliferation in SW-480 cells. We report the inhibition of ERK1/2/JNK/AP-1 pathway as a possible mechanism behind the anticancer as well as chemopreventive efficacy of [6]-gingerol against colon cancer.

Selenium and Prostate Cancer Prevention: Insights from the Selenium and Vitamin E Cancer Prevention Trial (SELECT)

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Nicastro, Holly L.; Dunn, Barbara K.

2013-01-01

The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was conducted to assess the efficacy of selenium and vitamin E alone, and in combination, on the incidence of prostate cancer. This randomized, double-blind, placebo-controlled, 2 × 2 factorial design clinical trial found that neither selenium nor vitamin E reduced the incidence of prostate cancer after seven years and that vitamin E was associated with a 17% increased risk of prostate cancer compared to placebo. The null result was surprising given the strong preclinical and clinical evidence suggesting chemopreventive activity of selenium. Potential explanations for the null findings include the agent formulation and dose, the characteristics of the cohort, and the study design. It is likely that only specific subpopulations may benefit from selenium supplementation; therefore, future studies should consider the baseline selenium status of the participants, age of the cohort, and genotype of specific selenoproteins, among other characteristics, in order to determine the activity of selenium in cancer prevention. PMID:23552052

Selenium and Prostate Cancer Prevention: Insights from the Selenium and Vitamin E Cancer Prevention Trial (SELECT

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Holly L. Nicastro

2013-04-01

Full Text Available The Selenium and Vitamin E Cancer Prevention Trial (SELECT was conducted to assess the efficacy of selenium and vitamin E alone, and in combination, on the incidence of prostate cancer. This randomized, double-blind, placebo-controlled, 2 × 2 factorial design clinical trial found that neither selenium nor vitamin E reduced the incidence of prostate cancer after seven years and that vitamin E was associated with a 17% increased risk of prostate cancer compared to placebo. The null result was surprising given the strong preclinical and clinical evidence suggesting chemopreventive activity of selenium. Potential explanations for the null findings include the agent formulation and dose, the characteristics of the cohort, and the study design. It is likely that only specific subpopulations may benefit from selenium supplementation; therefore, future studies should consider the baseline selenium status of the participants, age of the cohort, and genotype of specific selenoproteins, among other characteristics, in order to determine the activity of selenium in cancer prevention.

Ursodeoxycholic acid in patients with ulcerative colitis and primary sclerosing cholangitis for prevention of colon cancer: a meta-analysis.

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Ashraf, Imran; Choudhary, Abhishek; Arif, Murtaza; Matteson, Michelle L; Hammad, Hazem T; Puli, Srinivas R; Bechtold, Matthew L

2012-04-01

Colon cancer risk is high in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). Ursodeoxycholic acid has been shown to have some promise as a chemopreventive agent. A meta-analysis was performed to compare the efficacy of ursodeoxycholic acid in the prevention of colonic neoplasia in patients with UC and PSC. Multiple databases were searched (January 2011). Studies examining the use of ursodeoxycholic acid vs. no ursodeoxycholic acid or placebo in adult patients with UC and PSC were included. Data were extracted in standard forms by two independent reviewers. Meta-analysis for the effect of ursodeoxycholic acid was performed by calculating pooled estimates of adenoma or colon cancer formation by odds ratio (OR) with random effects model. Heterogeneity was assessed by calculating the I (2) measure of inconsistency. RevMan 5 was utilized for statistical analysis. Four studies (n = 281) met the inclusion criteria. The studies were of adequate quality. Ursodeoxycholic acid demonstrated no overall improvement in adenoma (OR 0.53; 95 % CI: 0.19-1.48, p = 0.23) or colon cancer occurrence (OR 0.50; 95 % CI: 0.18-1.43, p = 0.20) as compared to no ursodeoxycholic acid or placebo in patients with UC and PSC. Ursodeoxycholic acid use in patients with UC and PSC does not appear to decrease the risk of adenomas or colon cancer.

Natural killer cells as a promising tool to tackle cancer-A review of sources, methodologies, and potentials.

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Preethy, Senthilkumar; Dedeepiya, Vidyasagar Devaprasad; Senthilkumar, Rajappa; Rajmohan, Mathaiyan; Karthick, Ramalingam; Terunuma, Hiroshi; Abraham, Samuel J K

2017-07-04

Immune cell-based therapies are emerging as a promising tool to tackle malignancies, both solid tumors and selected hematological tumors. Vast experiences in literature have documented their safety and added survival benefits when such cell-based therapies are combined with the existing treatment options. Numerous methodologies of processing and in vitro expansion protocols of immune cells, such as the dendritic cells, natural killer (NK) cells, NKT cells, αβ T cells, so-called activated T lymphocytes, γδ T cells, cytotoxic T lymphocytes, and lymphokine-activated killer cells, have been reported for use in cell-based therapies. Among this handful of immune cells of significance, the NK cells stand apart from the rest for not only their direct cytotoxic ability against cancer cells but also their added advantage, which includes their capability of (i) action through both innate and adaptive immune mechanism, (ii) tackling viruses too, giving benefits in conditions where viral infections culminate in cancer, and (iii) destroying cancer stem cells, thereby preventing resistance to chemotherapy and radiotherapy. This review thoroughly analyses the sources of such NK cells, methods for expansion, and the future potentials of taking the in vitro expanded allogeneic NK cells with good cytotoxic ability as a drug for treating cancer and/or viral infection and even as a prophylactic tool for prevention of cancer after initial remission.

Lipid-based oral delivery systems for skin deposition of a potential chemopreventive DIM derivative: characterization and evaluation.

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Boakye, Cedar H A; Patel, Ketan; Patel, Apurva R; Faria, Henrique A M; Zucolotto, Valtencir; Safe, Stephen; Singh, Mandip

2016-10-01

The objective of this study was to explore the oral route as a viable potential for the skin deposition of a novel diindolylmethane derivative (DIM-D) for chemoprevention activity. Various lipid-based oral delivery systems were optimized and compared for enhancing DIM-D's oral bioavailability and skin deposition. Preformulation studies were performed to evaluate the log P and solubility of DIM-D. Microsomal metabolism, P-glycoprotein efflux, and caco-2 monolayer permeability of DIM-D were determined. Comparative evaluation of the oral absorption and skin deposition of DIM-D-loaded various lipid-based formulations was performed in rats. DIM-D showed pH-dependent solubility and a high log P value. It was not a strong substrate of microsomal degradation and P-glycoprotein. SMEDDs comprised of medium chain triglycerides, monoglycerides, and kolliphor-HS15 (36.70 ± 0.42 nm). SNEDDs comprised of long chain triglycerides, cremophor RH40, labrasol, and TPGS (84.00 ± 14.14 nm). Nanostructured lipid carriers (NLC) consisted of compritol, miglyol, and surfactants (116.50 ± 2.12 nm). The blank formulations all showed >70 % cell viability in caco-2 cells. Differential Scanning Calorimetry confirmed the amorphization of DIM-D within the lipid matrices while Atomic Force Microscopy showed particle size distribution similar to the dynamic light scattering data. DIM-D also showed reduced permeation across caco-2 monolayer that was enhanced (p < 0.05) by SNEDDs in comparison to SMEDDs and NLC. Fabsolute for DIM-D SNEDDs, SMEDDs, and NLC was 0.14, 0.04, and 0.007, respectively. SNEDDs caused 53.90, 11.32, and 15.08-fold more skin deposition of DIM-D than the free drug, SMEDDs, and NLC, respectively, at 2 h following oral administration and shows a viable potential for use in skin cancer chemoprevention. Graphical Abstract ᅟ.

A review of the dietary flavonoid, kaempferol on human health and cancer chemoprevention

OpenAIRE

Chen, Allen Y.; Chen, Yi Charlie

2012-01-01

Kaempferol is a polyphenol antioxidant found in fruits and vegetables. Many studies have described the beneficial effects of dietary kaempferol in reducing the risk of chronic diseases, especially cancer. Epidemiological studies have shown an inverse relationship between kaempferol intake and cancer. Kaempferol may help by augmenting the body’s antioxidant defense against free radicals, which promote the development of cancer. At the molecular level, kaempferol has been reported to modulate a...

A nanobody targeting carcinoembryonic antigen as a promising molecular probe for non-small cell lung cancer.

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Wang, Hao; Meng, Ai-Min; Li, Sheng-Hua; Zhou, Xiao-Liang

2017-07-01

Carcinoembryonic antigen (CEA) is a biomarker and therapy target for non‑small cell lung cancer (NSCLC), which is the most common type of lung cancer. Nanobodies with high target specificity are promising candidates to function as anti‑CEA probes. In the present study, the targeting effects of an anti‑CEA nanobody obtained from phage display were investigated using technetium‑99 m (99mTc) and fluorescence labeling. In vitro binding and immunofluorescent staining assays, as well as in vivo blood clearance and biodistribution assays were performed. High specificity and affinity of the nanobody for CEA‑positive H460 cells was observed in vitro. The pharmacokinetics assay of the 99mTc‑nanobody in Wistar rats demonstrated that the nanobody had appropriate T1/2α and T1/2β, which were 20.2 and 143.5 min, respectively. The biodistribution assay using H460 xenograft‑bearing nude mice demonstrated a high ratio of signal in tumor compared with background, which confirmed that the nanobody may be useful as a molecular probe for CEA‑positive cancer, particularly in NSCLC.

Cross-species global and subset gene expression profiling identifies genes involved in prostate cancer response to selenium

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Dhir Rajiv

2004-08-01

Full Text Available Abstract Background Gene expression technologies have the ability to generate vast amounts of data, yet there often resides only limited resources for subsequent validation studies. This necessitates the ability to perform sorting and prioritization of the output data. Previously described methodologies have used functional pathways or transcriptional regulatory grouping to sort genes for further study. In this paper we demonstrate a comparative genomics based method to leverage data from animal models to prioritize genes for validation. This approach allows one to develop a disease-based focus for the prioritization of gene data, a process that is essential for systems that lack significant functional pathway data yet have defined animal models. This method is made possible through the use of highly controlled spotted cDNA slide production and the use of comparative bioinformatics databases without the use of cross-species slide hybridizations. Results Using gene expression profiling we have demonstrated a similar whole transcriptome gene expression patterns in prostate cancer cells from human and rat prostate cancer cell lines both at baseline expression levels and after treatment with physiologic concentrations of the proposed chemopreventive agent Selenium. Using both the human PC3 and rat PAII prostate cancer cell lines have gone on to identify a subset of one hundred and fifty-four genes that demonstrate a similar level of differential expression to Selenium treatment in both species. Further analysis and data mining for two genes, the Insulin like Growth Factor Binding protein 3, and Retinoic X Receptor alpha, demonstrates an association with prostate cancer, functional pathway links, and protein-protein interactions that make these genes prime candidates for explaining the mechanism of Selenium's chemopreventive effect in prostate cancer. These genes are subsequently validated by western blots showing Selenium based induction and using

Assessing barriers to a rational chemoprevention trial design in young patients with familial adenomatous polyposis.

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Wood, Joanna P; Howells, Lynne M; Brown, Karen; Thomas, Anne L

2017-07-01

Familial adenomatous polyposis coli (FAP) is an autosomal dominant condition caused by a germline mutation in the adenomatous polyposis coli gene. Colonic adenomas form and almost all patients will develop colorectal cancer if they are not managed at an early stage. The safest preventive strategy is surgical resection of the colon, most commonly performed in late teenage years. There is a paucity of trials investigating the use of primary chemoprevention to delay polyp formation in paediatric FAP. There are extensive preclinical and early clinical data demonstrating that curcumin may be a safe and effective chemotherapeutic agent in reducing the polyp burden in this disease. We ultimately proposed to design and conduct a clinical study to assess whether curcumin treatment delays the need for surgery and/or prevents cancer in young patients with FAP. Research into clinical trial protocols has demonstrated that assessing patients' perceptions at the initial stage leads to better outcomes. We therefore conducted a questionnaire study of patients and parents of children affected by FAP to gain information to aid the protocol design. Results demonstrated that there are some FAP patients for whom this study is relevant and desirable. Those with a personal history of curcumin use reported that it was well tolerated. However, the response rate was poor (25%), indicating that there are potential difficulties ensuring adequate recruitment to the proposed trial. This report draws on lessons learnt from prior trials and the findings from the questionnaire to outline the challenges faced in designing such a study.

Novel vitamin D compounds and skin cancer prevention

OpenAIRE

Tongkao-on, Wannit; Gordon-Thomson, Clare; Dixon, Katie M.; Song, Eric J.; Luu, Tan; Carter, Sally E.; Sequeira, Vanessa B.; Reeve, Vivienne E.; Mason, Rebecca S.

2013-01-01

As skin cancer is one of the most costly health issues in many countries, particularly in Australia, the possibility that vitamin D compounds might contribute to prevention of this disease is becoming increasingly more attractive to researchers and health communities. In this article, important epidemiologic, mechanistic and experimental data supporting the chemopreventive potential of several vitamin D-related compounds are explored. Evidence of photoprotection by the active hormone, 1α,25di...

Epigenetic effects of green tea polyphenols in cancer

Science.gov (United States)

Henning, Susanne M; Wang, Piwen; Carpenter, Catherine L; Heber, David

2014-01-01

Epigenetics describes heritable alterations of gene expression and chromatin organization without changes in DNA sequence. Both hypermethylation and hypomethylation of DNA can affect gene expression and the multistep process of carcinogenesis. Epigenetic changes are reversible and may be targeted by dietary interventions. Bioactive compounds from green tea (GT) such as (–)-epigallocatechin gallate have been shown to alter DNA methyltransferase activity in studies of esophageal, oral, skin, Tregs, lung, breast and prostate cancer cells, which may contribute to the chemopreventive effect of GT. Three out of four mouse model studies have confirmed the inhibitory effect of (–)-epigallocatechin gallate on DNA methylation. A human study demonstrated that decreased methylation of CDX2 and BMP-2 in gastric carcinoma was associated with higher GT consumption. It is the goal of this review to summarize our current knowledge of the potential of GT to alter epigenetic processes, which may be useful in chemoprevention. PMID:24283885

Potential Application of Curcumin and Its Analogues in the Treatment Strategy of Patients with Primary Epithelial Ovarian Cancer

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Terlikowska, Katarzyna M.; Witkowska, Anna M.; Zujko, Malgorzata E.; Dobrzycka, Bozena; Terlikowski, Slawomir J.

2014-01-01

Recent findings on the molecular basis of ovarian cancer development and progression create new opportunities to develop anticancer medications that would affect specific metabolic pathways and decrease side systemic toxicity of conventional treatment. Among new possibilities for cancer chemoprevention, much attention is paid to curcumin—A broad-spectrum anticancer polyphenolic derivative extracted from the rhizome of Curcuma longa L. According to ClinicalTrials.gov at present there are no running pilot studies, which could assess possible therapeutic benefits from curcumin supplementation to patients with primary epithelial ovarian cancer. Therefore, the goal of this review was to evaluate potential preclinical properties of curcumin and its new analogues on the basis of in vivo and in vitro ovarian cancer studies. Curcumin and its different formulations have been shown to display multifunctional mechanisms of anticancer activity, not only in platinum-resistant primary epithelial ovarian cancer, but also in multidrug resistant cancer cells/xenografts models. Curcumin administered together with platinum-taxane chemotherapeutics have been reported to demonstrate synergistic effects, sensitize resistant cells to drugs, and decrease their biologically effective doses. An accumulating body of evidence suggests that curcumin, due to its long-term safety and an excellent profile of side effects should be considered as a beneficial support in ovarian cancer treatment strategies, especially in patients with platinum-resistant primary epithelial recurrent ovarian cancer or multidrug resistant disease. Although the prospect of curcumin and its formulations as anticancer agents in ovarian cancer treatment strategy appears to be challenging, and at the same time promising, there is a further need to evaluate its effectiveness in clinical studies. PMID:25429431

Therapeutic targeting of angiotensin II receptor type 1 to regulate androgen receptor in prostate cancer.

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Takahashi, Satoru; Uemura, Hiroji; Seeni, Azman; Tang, Mingxi; Komiya, Masami; Long, Ne; Ishiguro, Hitoshi; Kubota, Yoshinobu; Shirai, Tomoyuki

2012-10-01

With the limited strategies for curative treatment of castration-resistant prostate cancer (CRPC), public interest has focused on the potential prevention of prostate cancer. Recent studies have demonstrated that an angiotensin II receptor blocker (ARB) has the potential to decrease serum prostate-specific antigen (PSA) level and improve performance status in CRPC patients. These facts prompted us to investigate the direct effects of ARBs on prostate cancer growth and progression. Transgenic rat for adenocarcinoma of prostate (TRAP) model established in our laboratory was used. TRAP rats of 3 weeks of age received ARB (telmisartan or candesartan) at the concentration of 2 or 10 mg/kg/day in drinking water for 12 weeks. In vitro analyses for cell growth, ubiquitylation or reporter gene assay were performed using LNCaP cells. We found that both telmisartan and candesartan attenuated prostate carcinogenesis in TRAP rats by augmentation of apoptosis resulting from activation of caspases, inactivation of p38 MAPK and down-regulation of the androgen receptor (AR). Further, microarray analysis demonstrated up-regulation of estrogen receptor β (ERβ) by ARB treatment. In both parental and androgen-independent LNCaP cells, ARB inhibited both cell growth and AR-mediated transcriptional activity. ARB also exerted a mild additional effect on AR-mediated transcriptional activation by the ERβ up-regulation. An intervention study revealed that PSA progression was prolonged in prostate cancer patients given an ARB compared with placebo control. These data provide a new concept that ARBs are promising potential chemopreventive and chemotherapeutic agents for prostate cancer. Copyright © 2012 Wiley Periodicals, Inc.

Identification of an unintended consequence of Nrf2-directed cytoprotection against a key tobacco carcinogen plus a counteracting chemopreventive intervention

Science.gov (United States)

Paonessa, Joseph D.; Ding, Yi; Randall, Kristen L.; Munday, Rex; Argoti, Dayana; Vouros, Paul; Zhang, Yuesheng

2011-01-01

Nrf2 is a major cytoprotective gene and is a key chemopreventive target against cancer and other diseases. Here we show that Nrf2 faces a dilemma in defense against 4-aminobiphenyl (ABP), a major human bladder carcinogen from tobacco smoke and other environmental sources. While Nrf2 protected mouse liver against ABP (which is metabolically activated in liver), the bladder level of N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-ABP), the predominant ABP-DNA adduct formed in bladder cells and tissues, was markedly higher in Nrf2+/+ mice than in Nrf2−/− mice after ABP exposure. Notably, Nrf2 protected bladder cells against ABP in vitro. Mechanistic investigations showed that the dichotomous effects of Nrf2 could be explained at least partly by upregulation of UDP-glucuronosyltransferase (UGT). Nrf2 promoted conjugation of ABP with glucuronic acid in the liver, increasing urinary excretion of the conjugate. While glucuronidation of ABP and its metabolites is a detoxification process, these conjugates, which are excreted in urine, are known to be unstable in acidic urine, leading to delivery of the parent compounds to bladder. Hence, while higher liver UGT activity may protect the liver against ABP it increases bladder exposure to ABP. These findings raise concerns of potential bladder toxicity when Nrf2-activating chemopreventive agents are used in humans exposed to ABP, especially in smokers. We further demonstrate that 5,6-dihydrocyclopenta[c][1,2]-dithiole-3(4H)-thione (CPDT) significantly inhibits dG-C8-ABP formation in bladder cells and tissues, but does not appear to significantly modulate ABP-catalyzing UGT in liver. Thus, CPDT exemplifies a counteracting solution to the dilemma posed by Nrf2. PMID:21487034

Mangiferin exerts antitumor activity in breast cancer cells by regulating matrix metalloproteinases, epithelial to mesenchymal transition, and β-catenin signaling pathway

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Li, Hongzhong; Huang, Jing; Yang, Bing; Xiang, Tingxiu; Yin, Xuedong; Peng, Weiyan; Cheng, Wei [Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Wan, Jingyuan; Luo, Fuling [Department of Pharmacology, Chongqing Medical University, Chongqing (China); Li, Hongyuan [Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Ren, Guosheng, E-mail: rgs726@163.com [Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China)

2013-10-01

Although mangiferin which is a naturally occurring glucosylxanthone has exhibited promising anticancer activities, the detailed molecular mechanism of mangiferin on cancers still remains enigmatic. In this study, the anticancer activity of mangiferin was evaluated in breast cancer cell line-based in vitro and in vivo models. We showed that mangiferin treatment resulted in decreased cell viability and suppression of metastatic potential in breast cancer cells. Further mechanistic investigation revealed that mangiferin induced decreased matrix metalloproteinase (MMP)-7 and -9, and reversal of epithelial–mesenchymal transition (EMT). Moreover, it was demonstrated that mangiferin significantly inhibited the activation of β-catenin pathway. Subsequent experiments showed that inhibiting β-catenin pathway might play a central role in mangiferin-induced anticancer activity through modulation of MMP-7 and -9, and EMT. Consistent with these findings in vitro, the antitumor potential was also verified in mangiferin-treated MDA-MB-231 xenograft mice where significantly decreased tumor volume, weight and proliferation, and increased apoptosis were obtained, with lower expression of MMP-7 and -9, vimentin and active β-catenin, and higher expression of E-cadherin. Taken together, our study suggests that mangiferin might be used as an effective chemopreventive agent against breast cancer. - Highlights: • Mangiferin inhibits growth and metastatic potential in breast cancer cells. • Mangiferin down-regulates MMP-7 and -9 in breast cancer cells. • Mangiferin induces the reversal of EMT in metastatic breast cancer cells. • Mangiferin inhibits the activation of β-catenin pathway in breast cancer cells. • Inhibiting β-catenin is responsible for the antitumor activity of mangiferin.

Pomegranate Extracts and Cancer Prevention: Molecular and Cellular Activities

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Syed, Deeba N.; Chamcheu, Jean-Christopher; Adhami, Vaqar M.; Mukhtar, Hasan

2014-01-01

There is increased appreciation by the scientific community that dietary phytochemicals can be potential weapons in the fight against cancer. Emerging data has provided new insights into the molecular and cellular framework needed to establish novel mechanism-based strategies for cancer prevention by selective bioactive food components. The unique chemical composition of the pomegranate fruit, rich in antioxidant tannins and flavonoids has drawn the attention of many investigators. Polyphenol rich fractions derived from the pomegranate fruit have been studied for their potential chemopreventive and/or cancer therapeutic effects in several animal models. Although data from in vitro and in vivo studies look convincing, well designed clinical trials in humans are needed to ascertain whether pomegranate can become part of our armamentarium against cancer. This review summarizes the available literature on the effects of pomegranate against various cancers. PMID:23094914

Colorectal Cancer Chemoprevention by Mesalazine and Its Derivatives

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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.

Chemoprevention of Basal and Squamous Cell Carcinoma With a Single Course of Fluorouracil, 5%, Cream: A Randomized Clinical Trial.

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Weinstock, Martin A; Thwin, Soe Soe; Siegel, Julia A; Marcolivio, Kimberly; Means, Alexander D; Leader, Nicholas F; Shaw, Fiona M; Hogan, Daniel; Eilers, David; Swetter, Susan M; Chen, Suephy C; Jacob, Sharon E; Warshaw, Erin M; Stricklin, George P; Dellavalle, Robert P; Sidhu-Malik, Navjeet; Konnikov, Nellie; Werth, Victoria P; Keri, Jonette E; Robinson-Bostom, Leslie; Ringer, Robert J; Lew, Robert A; Ferguson, Ryan; DiGiovanna, John J; Huang, Grant D

2018-02-01

Keratinocyte carcinoma (ie, cutaneous basal and squamous cell carcinoma) is the most common cancer in the United States. To determine whether topical fluorouracil could prevent surgically treated keratinocyte carcinoma. The Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial was a randomized, double-blind, placebo-controlled trial of topical fluorouracil for chemoprevention of keratinocyte carcinoma. Participants were recruited from May 2009 to September 2011 from 12 Veterans Affairs medical centers and followed until June 30, 2013. Participants were veterans (n = 932) with a history of at least 2 keratinocyte carcinomas in the past 5 years; almost all were white males and the median age was 70 years. Application of fluorouracil, 5%, (n = 468) or vehicle control cream (n = 464) to the face and ears twice daily for 2 to 4 weeks upon randomization. Surgically treated keratinocyte, basal cell, and squamous cell carcinoma risk on the face and ears in the first year after enrollment; and time to first surgically treated keratinocyte, basal cell, and squamous cell carcinoma. The a priori hypothesis was that fluorouracil would be effective in preventing these cancers. Of 932 participants (916 men [98%]; 926 white [99%]; median age, 70 years), 299 developed a basal cell carcinoma end point (95 in year 1) and 108 developed a squamous cell carcinoma end point (25 in year 1) over 4 years (median follow-up, 2.8 years). Over the entire study, there was no difference between treatment groups in time to first keratinocyte, basal cell, or squamous cell carcinoma. During the first year, however, 5 participants (1%) in the fluorouracil group developed a squamous cell carcinoma vs 20 (4%) in the control group, a 75% (95% CI, 35%-91%) risk reduction (P = .002). The 11% reduction in basal cell carcinoma risk during year 1 (45 [10%] in the fluorouracil group vs 50 [11%] in the control group) was not statistically significant (95% CI, 39% reduction to 31

The chemopreventive potential of Curcuma purpurascens rhizome in reducing azoxymethane-induced aberrant crypt foci in rats

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Rouhollahi, Elham; Moghadamtousi, Soheil Zorofchian; Al-Henhena, Nawal; Kunasegaran, Thubasni; Hasanpourghadi, Mohadeseh; Looi, Chung Yeng; Abd Malek, Sri Nurestri; Awang, Khalijah; Abdulla, Mahmood Ameen; Mohamed, Zahurin

2015-01-01

Curcuma purpurascens BI. rhizome, a member of the Zingiberaceae family, is a popular spice in Indonesia that is traditionally used in assorted remedies. Dichloromethane extract of C. purpurascens BI. rhizome (DECPR) has previously been shown to have an apoptosis-inducing effect on colon cancer cells. In the present study, we examined the potential of DECPR to prevent colon cancer development in rats treated with azoxymethane (AOM) (15 mg/kg) by determining the percentage inhibition in incidence of aberrant crypt foci (ACF). Starting from the day immediately after AOM treatment, three groups of rats were orally administered once a day for 2 months either 10% Tween 20 (5 mL/kg, cancer control), DECPR (250 mg/kg, low dose), or DECPR (500 mg/kg, high dose). Meanwhile, the control group was intraperitoneally injected with 5-fluorouracil (35 mg/kg) for 5 consecutive days. After euthanizing the rats, the number of ACF was enumerated in colon tissues. Bax, Bcl-2, and proliferating cell nuclear antigen (PCNA) protein expressions were examined using immunohistochemical and Western blot analyses. Antioxidant enzymatic activity was measured in colon tissue homogenates and associated with malondialdehyde level. The percentage inhibition of ACF was 56.04% and 68.68% in the low- and high-dose DECPR-treated groups, respectively. The ACF inhibition in the treatment control group was 74.17%. Results revealed that DECPR exposure at both doses significantly decreased AOM-induced ACF formation, which was accompanied by reduced expression of PCNA. Upregulation of Bax and downregulation of Bcl-2 suggested the involvement of apoptosis in the chemopreventive effect of DECPR. In addition, the oxidative stress resulting from AOM treatment was significantly attenuated after administration of DECPR, which was shown by the elevated antioxidant enzymatic activity and reduced malondialdehyde level. Taken together, the present data clearly indicate that DECPR significantly inhibits ACF formation

ADA-07 Suppresses Solar Ultraviolet-Induced Skin Carcinogenesis by Directly Inhibiting TOPK.

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Gao, Ge; Zhang, Tianshun; Wang, Qiushi; Reddy, Kanamata; Chen, Hanyong; Yao, Ke; Wang, Keke; Roh, Eunmiri; Zykova, Tatyana; Ma, Weiya; Ryu, Joohyun; Curiel-Lewandrowski, Clara; Alberts, David; Dickinson, Sally E; Bode, Ann M; Xing, Ying; Dong, Zigang

2017-09-01

Cumulative exposure to solar ultraviolet (SUV) irradiation is regarded as the major etiologic factor in the development of skin cancer. The activation of the MAPK cascades occurs rapidly and is vital in the regulation of SUV-induced cellular responses. The T-LAK cell-originated protein kinase (TOPK), an upstream activator of MAPKs, is heavily involved in inflammation, DNA damage, and tumor development. However, the chemopreventive and therapeutic effects of specific TOPK inhibitors in SUV-induced skin cancer have not yet been elucidated. In the current study, ADA-07, a novel TOPK inhibitor, was synthesized and characterized. Pull-down assay results, ATP competition, and in vitro kinase assay data revealed that ADA-07 interacted with TOPK at the ATP-binding pocket and inhibited its kinase activity. Western blot analysis showed that ADA-07 suppressed SUV-induced phosphorylation of ERK1/2, p38, and JNKs and subsequently inhibited AP-1 activity. Importantly, topical treatment with ADA-07 dramatically attenuated tumor incidence, multiplicity, and volume in SKH-1 hairless mice exposed to chronic SUV. Our findings suggest that ADA-07 is a promising chemopreventive or potential therapeutic agent against SUV-induced skin carcinogenesis that acts by specifically targeting TOPK. Mol Cancer Ther; 16(9); 1843-54. ©2017 AACR . ©2017 American Association for Cancer Research.

DuCLOX-2/5 Inhibition Attenuates Inflammatory Response and Induces Mitochondrial Apoptosis for Mammary Gland Chemoprevention

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Swetlana Gautam

2018-04-01

Full Text Available The present study is a pursuit to define implications of dual cyclooxygenase-2 (COX-2 and 5-lipoxygenase (5-LOX (DuCLOX-2/5 inhibition on various aspects of cancer augmentation and chemoprevention. The monotherapy and combination therapy of zaltoprofen (COX-2 inhibitor and zileuton (5-LOX inhibitor were validated for their effect against methyl nitrosourea (MNU induced mammary gland carcinoma in albino wistar rats. The combination therapy demarcated significant effect upon the cellular proliferation as evidenced through decreased in alveolar bud count and restoration of the histopathological architecture when compared to toxic control. DuCLOX-2/5 inhibition also upregulated levels of caspase-3 and caspase-8, and restored oxidative stress markers (GSH, TBARs, protein carbonyl, SOD and catalase. The immunoblotting and qRT-PCR studies revealed the participation of the mitochondrial mediated death apoptosis pathway along with favorable regulation of COX-2, 5-LOX. Aforementioned combination restored the metabolic changes to normal when scrutinized through 1H NMR studies. Henceforth, the DuCLOX-2/5 inhibition was recorded to import significant anticancer effects in comparison to either of the individual treatments.

Prevention of Gastric Cancer: Eradication of Helicobacter Pylori and Beyond

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Tetsuya Tsukamoto

2017-08-01

Full Text Available Although its prevalence is declining, gastric cancer remains a significant public health issue. The bacterium Helicobacter pylori is known to colonize the human stomach and induce chronic atrophic gastritis, intestinal metaplasia, and gastric cancer. Results using a Mongolian gerbil model revealed that H. pylori infection increased the incidence of carcinogen-induced adenocarcinoma, whereas curative treatment of H. pylori significantly lowered cancer incidence. Furthermore, some epidemiological studies have shown that eradication of H. pylori reduces the development of metachronous cancer in humans. However, other reports have warned that human cases of atrophic metaplastic gastritis are already at risk for gastric cancer development, even after eradication of these bacteria. In this article, we discuss the effectiveness of H. pylori eradication and the morphological changes that occur in gastric dysplasia/cancer lesions. We further assess the control of gastric cancer using various chemopreventive agents.

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

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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.

Targeting multiple pro-apoptotic signaling pathways with curcumin in prostate cancer cells.

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Mariela Rivera

Full Text Available Curcumin, an extract from the turmeric rhizome (Curcuma longa, is known to exhibit anti-inflammatory, antioxidant, chemopreventive and antitumoral activities against aggressive and recurrent cancers. Accumulative data indicate that curcumin may induce cancer cell death. However, the detailed mechanism underlying its pro-apoptotic and anti-cancer effects remains to be elucidated. In the present study, we examined the signaling pathways triggered by curcumin, specifically, the exact molecular mechanisms of curcumin-induced apoptosis in highly metastatic human prostate cancer cells. The effect of curcumin was evaluated using for the first time in prostate cancer, a gel-free shotgun quantitative proteomic analysis coupled with Tandem Mass Tag isobaric labeling-based-signaling networks. Results were confirmed at the gene expression level by qRT-PCR and at the protein expression level by western blot and flow cytometry. Our findings revealed that curcumin induced an Endoplasmic Reticulum stress-mediated apoptosis in PC3. The mechanisms by which curcumin promoted cell death in these cells were associated with cell cycle arrest, increased reactive oxygen species, autophagy and the Unfolded Protein Response. Furthermore, the upregulation of ER stress was measured using key indicators of ER stress: Glucose-Regulated Protein 78, Inositol-Requiring Enzyme 1 alpha, Protein Disulfide isomerase and Calreticulin. Chronic ER stress induction was concomitant with the upregulation of pro-apoptotic markers (caspases 3,9,12 and Poly (ADP-ribose polymerase. The downregulated proteins include anti-apoptotic and anti-tumor markers, supporting their curcumin-induced pro-apoptotic role in prostate cancer cells. Taken together, these data suggest that curcumin may serve as a promising anticancer agent by inducing a chronic ER stress mediated cell death and activation of cell cycle arrest, UPR, autophagy and oxidative stress responses.

Targeting multiple pro-apoptotic signaling pathways with curcumin in prostate cancer cells

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Rivera, Mariela; Ramos, Yanilda; Rodríguez-Valentín, Madeline; López-Acevedo, Sheila; Cubano, Luis A.; Zou, Jin; Zhang, Qiang; Wang, Guangdi

2017-01-01

Curcumin, an extract from the turmeric rhizome (Curcuma longa), is known to exhibit anti-inflammatory, antioxidant, chemopreventive and antitumoral activities against aggressive and recurrent cancers. Accumulative data indicate that curcumin may induce cancer cell death. However, the detailed mechanism underlying its pro-apoptotic and anti-cancer effects remains to be elucidated. In the present study, we examined the signaling pathways triggered by curcumin, specifically, the exact molecular mechanisms of curcumin-induced apoptosis in highly metastatic human prostate cancer cells. The effect of curcumin was evaluated using for the first time in prostate cancer, a gel-free shotgun quantitative proteomic analysis coupled with Tandem Mass Tag isobaric labeling-based-signaling networks. Results were confirmed at the gene expression level by qRT-PCR and at the protein expression level by western blot and flow cytometry. Our findings revealed that curcumin induced an Endoplasmic Reticulum stress-mediated apoptosis in PC3. The mechanisms by which curcumin promoted cell death in these cells were associated with cell cycle arrest, increased reactive oxygen species, autophagy and the Unfolded Protein Response. Furthermore, the upregulation of ER stress was measured using key indicators of ER stress: Glucose-Regulated Protein 78, Inositol-Requiring Enzyme 1 alpha, Protein Disulfide isomerase and Calreticulin. Chronic ER stress induction was concomitant with the upregulation of pro-apoptotic markers (caspases 3,9,12) and Poly (ADP-ribose) polymerase. The downregulated proteins include anti-apoptotic and anti-tumor markers, supporting their curcumin-induced pro-apoptotic role in prostate cancer cells. Taken together, these data suggest that curcumin may serve as a promising anticancer agent by inducing a chronic ER stress mediated cell death and activation of cell cycle arrest, UPR, autophagy and oxidative stress responses. PMID:28628644

Polyphenols from the Mediterranean herb rosemary (Rosmarinus officinalis for prostate cancer

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Sakina M Petiwala

2013-03-01

Full Text Available The Mediterranean diet is rich in fruits and vegetables and has been associated with a variety of health benefits including cancer prevention. One aspect of the diet that has not received enough attention is Mediterranean herbs. Specifically, rosemary and its polyphenolic diterpenes (carnosic acid and carnosol are known to possess antioxidant activity that may be beneficial for cancer control. Herein, we describe the in vitro and in vivo studies carried out towards understanding the molecular mechanisms of carnosic acid and carnosol leading to inhibition of prostate cancer. The reported findings suggest that these polyphenols target multiple signaling pathways involved in cell cycle modulation and apoptosis. Further work is required to understand its potential for health promotion and potential drug discovery for prostate cancer chemoprevention.

Ganoderma spp.: A Promising Adjuvant Treatment for Breast Cancer

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Suárez-Arroyo, Ivette J.; Loperena-Alvarez, Yaliz; Rosario-Acevedo, Raysa; Martínez-Montemayor, Michelle M.

2017-01-01

For the past several decades, cancer patients in the U.S. have chosen the use of natural products as an alternative or complimentary medicine approach to treat or improve their quality of life via reduction or prevention of the side effects during or after cancer treatment. The genus Ganoderma includes about 80 species of mushrooms, of which several have been used for centuries in traditional Asian medicine for their medicinal properties, including anticancer and immunoregulatory effects. Numerous bioactive compounds seem to be responsible for their healing effects. Among the approximately 400 compounds produced by Ganoderma spp., triterpenes, peptidoglycans and polysaccharides are the major physiologically-active constituents. Ganoderma anticancer effects are attributed to its efficacy in reducing cancer cell survival and growth, as well as by its chemosensitizing role. In vitro and in vivo studies have been conducted in various cancer cells and animal models; however, in this review, we focus on Ganoderma’s efficacy on breast cancers. Evidence shows that some species of Ganoderma have great potential as a natural therapeutic for breast cancer. Nevertheless, further studies are needed to investigate their potential in the clinical setting and to translate our basic scientific findings into therapeutic interventions for cancer patients. PMID:28758107

The ErbB family and androgen receptor signaling are targets of Celecoxib in prostate cancer.

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Brizzolara, Antonella; Benelli, Roberto; Venè, Roberta; Barboro, Paola; Poggi, Alessandro; Tosetti, Francesca; Ferrari, Nicoletta

2017-08-01

Inflammation plays a central role in prostate cancer (PCa) development through significant crosstalk between the COX-2-ErbB family receptor network and androgen receptor (AR)-EGFR signaling pathways. The purpose of this work was to determine the ability of the COX-2 inhibitor Celecoxib to modulate the EGFR-AR signaling pathway in androgen-dependent PCa cells and to provide a rationale for its beneficial use in chemopreventive strategies. Functional studies of Celecoxib activity were performed on LNCaP prostate cancer cells. Western blotting, gene expression analysis, dual-luciferase reporter assay and ELISA were applied to assess the Celecoxib mechanisms of action. We found that Celecoxib, through EGF and amphiregulin (AREG) induction, caused EGFR and ErbB2 activation and consequent degradation associated with the inhibition of androgenic signaling. By upregulating the E3 ubiquitin ligase Nrdp1, Celecoxib also efficiently downregulated ErbB3, which is strongly implicated in castration-resistant prostate cancer. Lastly, Celecoxib directly regulated AR transcription and translation independent of ErbB activation by downregulating the RNA binding protein heterogeneous nuclear ribonucleoprotein K (hnRNP K). The simultaneous suppression of ErbB kinases and androgen signaling by Celecoxib represents a novel strategy to interrupt the vicious cycle of AR/ErbB cross-talk with the primary purpose of undermining their resilient signaling in prostate cancer progression. Our data provide important premises for the chemopreventive use of Celecoxib in the clinical management of prostate cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Pharmacokinetics of dietary cancer chemopreventive compound dibenzoylmethane in rats and the impact of nanoemulsion and genetic knockout of Nrf2 on its disposition.

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Lin, Wen; Hong, Jin-Liern; Shen, Guoxiang; Wu, Rachel T; Wang, Yuwen; Huang, Mou-Tuan; Newmark, Harold L; Huang, Qingrong; Khor, Tin Oo; Heimbach, Tycho; Kong, Ah-Ng

2011-03-01

The pharmacokinetic disposition of a dietary cancer chemopreventive compound dibenzoylmethane (DBM) was studied in male Sprague-Dawley rats after intravenous (i.v.) and oral (p.o.) administrations. Following a single i.v. bolus dose, the mean plasma clearance (CL) of DBM was low compared with the hepatic blood flow. DBM displayed a high volume of distribution (Vss). The elimination terminal t1/2 was long. The mean CL, Vss and AUC0-∞/dose were similar between the i.v. 10 and 10 mg/kg doses. After single oral doses (10, 50 and 250 mg/kg), the absolute oral bioavailability (F*) of DBM was 7.4%-13.6%. The increase in AUC was not proportional to the oral doses, suggesting non-linearity. In silico prediction of oral absorption also demonstrated low DBM absorption in vivo. An oil-in-water nanoemulsion containing DBM was formulated to potentially overcome the low F* due to poor water solubility of DBM, with enhanced oral absorption. Finally, to examine the role of Nrf2 on the pharmacokinetics of DBM, since DBM activates the Nrf2-dependent detoxification pathways, Nrf2 wild-type (+/+) mice and Nrf2 knockout (-/-) mice were utilized. There was an increased systemic plasma exposure of DBM in Nrf2 (-/-) mice, suggesting that the Nrf2 genotype could also play a role in the pharmacokinetic disposition of DBM. Taken together, the results show that DBM has low oral bioavailability which could be due in part to poor water solubility and this could be overcome by a nanotechnology-based drug delivery system and furthermore the Nrf2 genotype could also play a role in the pharmacokinetics of DBM. Copyright © 2010 John Wiley & Sons, Ltd.

Polyether ionophores-promising bioactive molecules for cancer therapy.

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Huczyński, Adam

2012-12-01

The natural polyether ionophore antibiotics might be important chemotherapeutic agents for the treatment of cancer. In this article, the pharmacology and anticancer activity of the polyether ionophores undergoing pre-clinical evaluation are reviewed. Most of polyether ionophores have shown potent activity against the proliferation of various cancer cells, including those that display multidrug resistance (MDR) and cancer stem cells (CSC). The mechanism underlying the anticancer activity of ionophore agents can be related to their ability to form complexes with metal cations and transport them across cellular and subcellular membranes. Increasing evidence shows that the anticancer activity of polyether ionophores may be a consequence of the induction of apoptosis leading to apoptotic cell death, arresting cell cycle progression, induction of the cell oxidative stress, loss of mitochondrial membrane potential, reversion of MDR, synergistic anticancer effect with other anticancer drugs, etc. Continued investigation of the mechanisms of action and development of new polyether ionophores and their derivatives may provide more effective therapeutic drugs for cancer treatments. Copyright © 2012 Elsevier Ltd. All rights reserved.

Fructose-Coated Nanodiamonds: Promising Platforms for Treatment of Human Breast Cancer.

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Zhao, Jiacheng; Lai, Haiwang; Lu, Hongxu; Barner-Kowollik, Christopher; Stenzel, Martina H; Xiao, Pu

2016-09-12

Well-defined carboxyl end-functionalized glycopolymer Poly(1-O-methacryloyl-2,3:4,5-di-O-isopropylidene-β-d-fructopyranose) (Poly(1-O-MAipFru)62) has been prepared via reversible addition-fragmentation chain transfer polymerization and grafted onto the surface of amine-functionalized nanodiamonds via a simple conjugation reaction. The properties of the nanodiamond-polymer hybrid materials ND-Poly(1-O-MAFru)62 are investigated using infrared spectroscopy, thermogravimetric analysis, dynamic light scattering, and transmission electron microscopy. The dispersibility of the nanodiamonds in aqueous solutions is significantly improved after the grafting of the glycopolymer. More interestingly, the cytotoxicity of amine-functionalized nanodiamonds is significantly decreased after decoration with the glycopolymer even at a high concentration (125 μg/mL). The nanodiamonds were loaded with doxorubicin to create a bioactive drug delivery carrier. The release of doxorubicin was faster in media of pH 5 than media of pH 7.4. The nanodiamond drug delivery systems with doxorubicin are used to treat breast cancer cells in 2D and 3D models. Although the 2D cell culture results indicate that all nanodiamonds-doxorubicin complexes are significantly less toxic than free doxorubicin, the glycopolymer-coated nanodiamonds-doxorubicin show higher cytotoxicity than free doxorubicin in the 3D spheroids after treatment for 8 days. The enhanced cytotoxicity of Poly(1-O-MAFru)62-ND-Dox in 3D spheroids may result from the sustained drug release and deep penetration of these nanocarriers, which play a role as a "Trojan Horse". The massive cell death after 8-day incubation with Poly(1-O-MAFru)62-ND-Dox demonstrates that glycopolymer-coated nanodiamonds can be promising platforms for breast cancer therapy.

Inhibition of Sphingolipid Metabolism Enhances Resveratrol Chemotherapy in Human Gastric Cancer Cells

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Shin, Kyong-Oh; Park, Nam-Young; Seo, Cho-Hee; Hong, Seon-Pyo; Oh, Ki-Wan; Hong, Jin-Tae; Han, Sang-Kil; Lee, Yong-Moon

2012-01-01

Resveratrol, a chemopreventive agent, is rapidly metabolized in the intestine and liver via glucuronidation. Thus, the pharmacokinetics of resveratrol limits its efficacy. To improve efficacy, the activity of resveratrol was investigated in the context of sphingolipid metabolism in human gastric cancer cells. Diverse sphingolipid metabolites, including dihydroceramides (DHCer), were tested for their ability to induce resveratrol cytotoxicity. Exposure to resveratrol (100 ?M) for 24 hr induced...

Phenolic extract from oleaster (Olea europaea var. Sylvestris) leaves reduces colon cancer growth and induces caspase-dependent apoptosis in colon cancer cells via the mitochondrial apoptotic pathway.

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Zeriouh, Wafa; Nani, Abdelhafid; Belarbi, Meriem; Dumont, Adélie; de Rosny, Charlotte; Aboura, Ikram; Ghanemi, Fatima Zahra; Murtaza, Babar; Patoli, Danish; Thomas, Charles; Apetoh, Lionel; Rébé, Cédric; Delmas, Dominique; Khan, Naim Akhtar; Ghiringhelli, François; Rialland, Mickael; Hichami, Aziz

2017-01-01

Dietary polyphenols, derived from natural products, have received a great interest for their chemopreventive properties against cancer. In this study, we investigated the effects of phenolic extract of the oleaster leaves (PEOL) on tumor growth in mouse model and on cell death in colon cancer cell lines. We assessed the effect of oleaster leaf infusion on HCT116 (human colon cancer cell line) xenograft growth in athymic nude mice. We observed that oleaster leaf polyphenol-rich infusion limited HCT116 tumor growth in vivo. Investigations of PEOL on two human CRC cell lines showed that PEOL induced apoptosis in HCT116 and HCT8 cells. We demonstrated an activation of caspase-3, -7 and -9 by PEOL and that pre-treatment with the pan-caspase inhibitor, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD-fmk), prevented PEOL-induced cell death. We observed an involvement of the mitochondrial pathway in PEOL-induced apoptosis evidenced by reactive oxygen species (ROS) production, a decrease of mitochondrial membrane potential, and cytochrome c release. Increase in intracellular Ca2+ concentration induced by PEOL represents the early event involved in mitochondrial dysfunction, ROS-induced endoplasmic reticulum (ER) stress and apoptosis induced by PEOL, as ruthenium red, an inhibitor of mitochondrial calcium uptake inhibited apoptotic effect of PEOL, BAPTA/AM inhibited PEOL-induced ROS generation and finally, N-acetyl-L-cysteine reversed ER stress and apoptotic effect of PEOL. These results demonstrate that polyphenols from oleaster leaves might have a strong potential as chemopreventive agent in colorectal cancer.

Performance of gadofosveset-enhanced MRI for staging rectal cancer nodes: can the initial promising results be reproduced?

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Heijnen, Luc A.; Martens, Milou H. [Maastricht University Medical Center, Department of Radiology, P.O. Box 5800, Maastricht (Netherlands); Maastricht University Medical Center, Department of Surgery, Maastricht (Netherlands); GROW School for Oncology and Developmental Biology, Maastricht (Netherlands); Lambregts, Doenja M.J.; Maas, Monique; Bakers, Frans C.H. [Maastricht University Medical Center, Department of Radiology, P.O. Box 5800, Maastricht (Netherlands); Cappendijk, Vincent C. [Jeroen Bosch Ziekenhuis, Department of Radiology, ' s Hertogenbosch (Netherlands); Oliveira, Pedro [Instituto Portugues de Oncologia do Porto Francisco Gentil, Department of Radiology, Porto (Portugal); Lammering, Guido [Maastro Clinic, Radiation Oncology, Maastricht (Netherlands); GROW School for Oncology and Developmental Biology, Maastricht (Netherlands); Riedl, Robert G. [Maastricht University Medical Center, Department of Pathology, Maastricht (Netherlands); Beets, Geerard L. [Maastricht University Medical Center, Department of Surgery, Maastricht (Netherlands); GROW School for Oncology and Developmental Biology, Maastricht (Netherlands); Beets-Tan, Regina G.H. [Maastricht University Medical Center, Department of Radiology, P.O. Box 5800, Maastricht (Netherlands); GROW School for Oncology and Developmental Biology, Maastricht (Netherlands)

2014-02-15

A previous study showed promising results for gadofosveset-trisodium as a lymph node magnetic resonance imaging (MRI) contrast agent in rectal cancer. The aim of this study was to prospectively confirm the diagnostic performance of gadofosveset MRI for nodal (re)staging in rectal cancer in a second patient cohort. Seventy-one rectal cancer patients were prospectively included, of whom 13 (group I) underwent a primary staging gadofosveset MRI (1.5-T) followed by surgery (± preoperative 5 x 5 Gy) and 58 (group II) underwent both primary staging and restaging gadofosveset MRI after a long course of chemoradiotherapy followed by surgery. Nodal status was scored as (y)cN0 or (y)cN+ by two independent readers (R1, R2) with different experience levels. Results were correlated with histology on a node-by-node basis. Sensitivity, specificity and area under the receiver operating characteristics curve (AUC) were 94 %, 79 % and 0.89 for the more experienced R1 and 50 %, 83 % and 0.74 for the non-experienced R2. R2's performance improved considerably after a learning curve, to an AUC of 0.83. Misinterpretations mainly occurred in nodes located in the superior mesorectum, nodes located in between vessels and nodes containing micrometastases. This prospective study confirms the good diagnostic performance of gadofosveset MRI for nodal (re)staging in rectal cancer. (orig.)

Prevention of chinese green tea on 3,4-benzopyrene-induced lung cancer and its mechanism in animal model

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Qihua GU

2008-08-01

Full Text Available Background and objective Chinese green tea is one of the daily consumption beverages in the world and is considered a promising cancer chemopreventive agent. In the present study, we investigate the role of lung cancer prevention by green tea and its mechanism. Methods Three groups of female SD rats were kept with the same feed. Rats in group A were administrated with 1% green tea drinking, while in group B and group C with water only. Animals in group A and group B were given 3,4-benzopyrene-corn oil mixture pulmonary injection fortnightly for 4 times, while in group C corn oil only. Rats were sacrificed 1 year after the first injection under narcotism. Lung tumors and lung tissues were performed H＆E staining for cancer identification. Each case of lung cancer was examined for expression of p53 and Bcl-2 with in situ hybridization analysis and immunohistochemistry staining. Results No cancer was found in rats in group C. However, in group B, 15 out of 20 rats were found generating lung cancer, and in group A, 6 out of 20 rats inducing lung cancer were recorded. The rate of lung carcinogenesis in rats was decreased from 75% to 30% by 1% chinese green tea oral administration (χ2=8.12, P0.05. However, significantly lower level of Bcl-2 expression was found in lung cancer tissues of group A than that of group B (P<0.05. Conclusion The results indicate that chinese green tea inhibits lung carcinogenesis. Chinese green tea can slightly upregulate expression of p53, but significantly downregulate expression of Bcl-2 in lung cancer, and this may be related to the mechanism of lung cancer prevention.

Roles of Dietary Phytoestrogens on the Regulation of Epithelial-Mesenchymal Transition in Diverse Cancer Metastasis

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Lee, Geum-A.; Hwang, Kyung-A.; Choi, Kyung-Chul

2016-01-01

Epithelial-mesenchymal transition (EMT) plays a key role in tumor progression. The cells undergoing EMT upregulate the expression of cell motility-related proteins and show enhanced migration and invasion. The hallmarks of EMT in cancer cells include changed cell morphology and increased metastatic capabilities in cell migration and invasion. Therefore, prevention of EMT is an important tool for the inhibition of tumor metastasis. A novel preventive therapy is needed, such as treatment of natural dietary substances that are nontoxic to normal human cells, but effective in inhibiting cancer cells. Phytoestrogens, such as genistein, resveratrol, kaempferol and 3,3′-diindolylmethane (DIM), can be raised as possible candidates. They are plant-derived dietary estrogens, which are found in tea, vegetables and fruits, and are known to have various biological efficacies, including chemopreventive activity against cancers. Specifically, these phytoestrogens may induce not only anti-proliferation, apoptosis and cell cycle arrest, but also anti-metastasis by inhibiting the EMT process in various cancer cells. There have been several signaling pathways found to be associated with the induction of the EMT process in cancer cells. Phytoestrogens were demonstrated to have chemopreventive effects on cancer metastasis by inhibiting EMT-associated pathways, such as Notch-1 and TGF-beta signaling. As a result, phytoestrogens can inhibit or reverse the EMT process by upregulating the expression of epithelial phenotypes, including E-cadherin, and downregulating the expression of mesenchymal phenotypes, including N-cadherin, Snail, Slug, and vimentin. In this review, we focused on the important roles of phytoestrogens in inhibiting EMT in many types of cancer and suggested phytoestrogens as prominent alternative compounds to chemotherapy. PMID:27231938

Promising Tools in Prostate Cancer Research

DEFF Research Database (Denmark)

Bonomo, Silvia; Hansen, Cecilie H; Petrunak, Elyse M

2016-01-01

Cytochrome P450 17A1 (CYP17A1) is an important target in the treatment of prostate cancer because it produces androgens required for tumour growth. The FDA has approved only one CYP17A1 inhibitor, abiraterone, which contains a steroidal scaffold similar to the endogenous CYP17A1 substrates...

Review article: colitis-associated cancer -- time for new strategies.

LENUS (Irish Health Repository)

Shanahan, F

2012-02-03

Colorectal cancer (CRC) remains a feared and potentially life-threatening complication of both ulcerative colitis and Crohn\\'s colitis. Currently, the main preventive strategy is a secondary one, i.e. surveillance colonoscopy usually after 8 years of disease duration, when the risk for neoplasia begins to increase. Despite its widespread acceptance, dysplasia and cancer surveillance is unproven in terms of reducing mortality or morbidity and there is a remarkable lack of uniformity in the manner in which it is practised. In this review article, the pitfalls of dysplasia surveillance are summarized and the need for novel chemopreventive and perhaps pharmabiotic approaches for prevention are highlighted.

Potential targets for colorectal cancer prevention.

Science.gov (United States)

Temraz, Sally; Mukherji, Deborah; Shamseddine, Ali

2013-08-22

The step-wise development of colorectal neoplasia from adenoma to carcinoma suggests that specific interventions could delay or prevent the development of invasive cancer. Several key factors involved in colorectal cancer pathogenesis have already been identified including cyclooxygenase 2 (COX-2), nuclear factor kappa B (NF-κB), survivin and insulin-like growth factor-I (IGF-I). Clinical trials of COX-2 inhibitors have provided the "proof of principle" that inhibition of this enzyme can prevent the formation of colonic adenomas and potentially carcinomas, however concerns regarding the potential toxicity of these drugs have limited their use as a chemopreventative strategy. Curcumin, resveratrol and quercetin are chemopreventive agents that are able to suppress multiple signaling pathways involved in carcinogenesis and hence are attractive candidates for further research.

Curcumin induces apoptosis-independent death in oesophageal cancer cells.

LENUS (Irish Health Repository)

O'Sullivan-Coyne, G

2009-10-06

Background:Oesophageal cancer incidence is increasing and survival rates remain extremely poor. Natural agents with potential for chemoprevention include the phytochemical curcumin (diferuloylmethane). We have examined the effects of curcumin on a panel of oesophageal cancer cell lines.Methods:MTT (3-(4,5-dimethyldiazol-2-yl)-2,5 diphenyl tetrazolium bromide) assays and propidium iodide staining were used to assess viability and DNA content, respectively. Mitotic catastrophe (MC), apoptosis and autophagy were defined by both morphological criteria and markers such as MPM-2, caspase 3 cleavage and monodansylcadaverine (MDC) staining. Cyclin B and poly-ubiquitinated proteins were assessed by western blotting.Results:Curcumin treatment reduces viability of all cell lines within 24 h of treatment in a 5-50 muM range. Cytotoxicity is associated with accumulation in G2\\/M cell-cycle phases and distinct chromatin morphology, consistent with MC. Caspase-3 activation was detected in two out of four cell lines, but was a minor event. The addition of a caspase inhibitor zVAD had a marginal or no effect on cell viability, indicating predominance of a non-apoptotic form of cell death. In two cell lines, features of both MC and autophagy were apparent. Curcumin-responsive cells were found to accumulate poly-ubiquitinated proteins and cyclin B, consistent with a disturbance of the ubiquitin-proteasome system. This effect on a key cell-cycle checkpoint regulator may be responsible for the mitotic disturbances and consequent cytotoxicity of this drug.Conclusion:Curcumin can induce cell death by a mechanism that is not reliant on apoptosis induction, and thus represents a promising anticancer agent for prevention and treatment of oesophageal cancer.British Journal of Cancer advance online publication, 6 October 2009; doi:10.1038\\/sj.bjc.6605308 www.bjcancer.com.

Health Promoting Effects of Brassica-Derived Phytochemicals: From Chemopreventive and Anti-Inflammatory Activities to Epigenetic Regulation

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Anika Eva Wagner

2013-01-01

Full Text Available A high intake of brassica vegetables may be associated with a decreased chronic disease risk. Health promoting effects of Brassicaceae have been partly attributed to glucosinolates and in particular to their hydrolyzation products including isothiocyanates. In vitro and in vivo studies suggest a chemopreventive activity of isothiocyanates through the redox-sensitive transcription factor Nrf2. Furthermore, studies in cultured cells, in laboratory rodents, and also in humans support an anti-inflammatory effect of brassica-derived phytochemicals. However, the underlying mechanisms of how these compounds mediate their health promoting effects are yet not fully understood. Recent findings suggest that brassica-derived compounds are regulators of epigenetic mechanisms. It has been shown that isothiocyanates may inhibit histone deacetylase transferases and DNA-methyltransferases in cultured cells. Only a few papers have dealt with the effect of brassica-derived compounds on epigenetic mechanisms in laboratory animals, whereas data in humans are currently lacking. The present review aims to summarize the current knowledge regarding the biological activities of brassica-derived phytochemicals regarding chemopreventive, anti-inflammatory, and epigenetic pathways.

Sulforaphane modulates telomerase activity via epigenetic regulation in prostate cancer cell lines.

Science.gov (United States)

Abbas, Ata; Hall, J Adam; Patterson, William L; Ho, Emily; Hsu, Anna; Al-Mulla, Fahd; Georgel, Philippe T

2016-02-01

Epidemiologic studies have revealed that diets rich in sulforaphane (SFN), an isothiocyanate present in cruciferous vegetables, are associated with a marked decrease in prostate cancer incidence. The chemo-preventive role of SFN is associated with its histone de-acetylase inhibitor activity. However, the effect of SFN on chromatin composition and dynamic folding, especially in relation to HDAC inhibitor activity, remains poorly understood. In this study, we found that SFN can inhibit the expression and activity of human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase, in 2 prostate cancer cell lines. This decrease in gene expression is correlated with SFN-induced changes in chromatin structure and composition. The SFN-mediated changes in levels of histone post-translational modifications, more specifically acetylation of histone H3 lysine 18 and di-methylation of histone H3 lysine 4, 2 modifications linked with high risk of prostate cancer recurrence, were associated with regulatory elements within the hTERT promoter region. Chromatin condensation may also play a role in SFN-mediated hTERT repression, since expression and recruitment of MeCP2, a known chromatin compactor, were altered in SFN treated prostate cancer cells. Chromatin immuno-precipitation (ChIP) of MeCP2 showed enrichment over regions of the hTERT promoter with increased nucleosome density. These combined results strongly support a role for SFN in the mediation of epigenetic events leading to the repression of hTERT in prostate cancer cells. This ability of SFN to modify chromatin composition and structure associated with target gene expression provides a new model by which dietary phytochemicals may exert their chemoprevention activity.

Kefir and Cancer: A Systematic Review of Literatures.

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Rafie, Nahid; Golpour Hamedani, Sahar; Ghiasvand, Reza; Miraghajani, Maryam

2015-12-01

Some studies have suggested chemopreventive effects of kefir, a fermented milk product, on carcinogenesis. The aim of this review study was to evaluate the scientific evidence for effects of kefir on cancer prevention and treatment. We systematically searched for all relevant studies published before June 2015, using PubMed, Google scholar, Cochrane and Science Direct, SID, MedLib and Srlst databases. Relevant studies were reviewed based on systematic review (PRISMA) guidelines. From a total of 2208 papers obtained at the initial database search, 11 publications including 7 in vitro and 4 experimental studies were eligible. In vitro studies on breast, colon, skin and gastric cancers and leukemia cell lines and experimental studies on different sarcomas consistently showed beneficial effects of kefir on cancer prevention and treatment. The results of this systematic review suggest that kefir may be associated with cancer prevention and it also has beneficial effects in cancer treatment. This protection may be associated with kefir bioactive components including peptides, polysaccharides and sphingolipids.

Norcantharidin, Derivative of Cantharidin, for Cancer Stem Cells

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Chen-Hsi Hsieh

2013-01-01

Full Text Available Cancer stem cells (CSCs existing in human cancers have been demonstrated to be a major cause of cancer treatment resistance, invasion, metastasis, and relapse. Self-renewal pathways, Wnt/β-catenin, Sonic hedgehog (Shh, and the Notch signaling pathway play critical roles in developing CSCs and lead to angiogenesis, migration, invasion, and metastasis. Multidrug resistance (MDR is an unfavorable factor causing the failure of treatments against cancer cells. The most important and thoroughly studied mechanism involved in MDR is the active efflux of chemotherapeutic agents through membrane drug transporters. There is growing evidence that Norcantharidin (NCTD, a water-soluble synthetic small molecule derivative of naturally occurring cantharidin from the medicinal insect blister beetle (Mylabris phalerata Pallas, is capable of chemoprevention and tumor inhibition. We summarize investigations into the modulation of self-renewal pathways and MDR in CSCs by NCTD. This review may aid in further investigation of using NCTD to develop more effective strategies for cancer treatment to reduce resistance and recurrence.

Assessment of cellular responses to oxidative stress using MCF-7 breast cancer cells, black seed (N. Sativa L.) extracts and H2O2.

Science.gov (United States)

Farah, Ibrahim O

2005-12-01

Black seed (N. Sativa L) is an oriental spice of the family Ranunculaceae that has long been rationally used as a natural medicine for treatment of many acute as well as chronic conditions including cardiovascular disease and immunological disorders. It has been used in the treatment of diabetes, hypertension, and dermatological conditions. There have been very few studies on the effects of N. Sativa as a chemoprevention of chronic diseases as well as in cancer prevention and/or therapy. Oxidative stress is a condition that underlies many acute as well as chronic conditions. The combination and role of oxidative stress and antioxidants in vivo is still a matter of conjecture. Our objective for the present study was to expose MCF-7 breast cancer cells in vitro (as a chronic disease example) to aqueous and alcohol extracts and in combination with H[2]O[2] as an oxidative stressor. Measurement of cell survival under various concentrations and mixtures was conducted using standard cell culture techniques, exposure protocols in 96 well plates and Fluorospectrosphotometry. Following cellular growth to 90% confluencey, exposure to water (WE) and ethanol (AE) extracts of N. sativa and H[2]O[2] was performed. Cell survival indices were calculated from percent survival using regression analysis. Results showed that the alcohol extract and its mixtures were able to influence the survival of MCF-7 cells (indices ranged from 357.15- 809.50 mug/ml in descending potency for H[2]O[2]+AE to the mix of 3). In contrast, H[2]O[2] alone reduced effectively the survival of MCF-7 cells and the least effective combinations in descending potency were AE+H[2]O[2], WE+H[2]O[2], AE+WE, and WE+AE+H[2]O[2]. Mixtures other than AE+H[2]O[2] showed possible interactions and loss of potency. In conclusion, N. Sativa alone or in combination with oxidative stress was found to be effective (in vitro) in influencing the survival of MCF-7 breast cancer cells, unveiling promising opportunities in the

Assessment of Cellular Responses to Oxidative Stress using MCF-7 Breast Cancer Cells, Black Seed (N. Sativa L. Extracts and H2O2

Directory of Open Access Journals (Sweden)

Ibrahim O. Farah

2005-12-01

Full Text Available Black seed (N. Sativa L is an oriental spice of the family Ranunculaceae that has long been rationally used as a natural medicine for treatment of many acute as well as chronic conditions including cardiovascular disease and immunological disorders. It has been used in the treatment of diabetes, hypertension, and dermatological conditions. There have been very few studies on the effects of N. Sativa as a chemoprevention of chronic diseases as well as in cancer prevention and/or therapy. Oxidative stress is a condition that underlies many acute as well as chronic conditions. The combination and role of oxidative stress and antioxidants in vivo is still a matter of conjecture. Our objective for the present study was to expose MCF-7 breast cancer cells in vitro (as a chronic disease example to aqueous and alcohol extracts and in combination with H2O2 as an oxidative stressor. Measurement of cell survival under various concentrations and mixtures was conducted using standard cell culture techniques, exposure protocols in 96 well plates and Fluorospectrosphotometry. Following cellular growth to 90% confluencey, exposure to water (WE and ethanol (AE extracts of N. sativa and H2O2 was performed. Cell survival indices were calculated from percent survival using regression analysis. Results showed that the alcohol extract and its mixtures were able to influence the survival of MCF-7 cells (indices ranged from 357.15- 809.50 Bg/ml in descending potency for H2O2+AE to the mix of 3. In contrast, H2O2 alone reduced effectively the survival of MCF-7 cells and the least effective combinations in descending potency were AE+H2O2, WE+H2O2, AE+WE, and WE+AE+H2O2. Mixtures other than AE+H2O2 showed possible interactions and loss of potency. In conclusion, N. Sativa alone or in combination with oxidative stress was found to be effective (in vitro in influencing the survival of MCF-7 breast cancer cells, unveiling promising opportunities in the field of cancer

3,3'-Diindolylmethane downregulates pro-survival pathway in hormone independent prostate cancer

International Nuclear Information System (INIS)

Garikapaty, Venkata P.S.; Ashok, Badithe T.; Tadi, Kiranmayi; Mittelman, Abraham; Tiwari, Raj K.

2006-01-01

Epidemiological evidences suggest that the progression and promotion of prostate cancer (CaP) can be modulated by diet. Since all men die with prostate cancer rather than of the disease, it is of particular interest to prevent or delay the progression of the disease by chemopreventive strategies. We have been studying the anticancer properties of compounds present in cruciferous vegetables such as indole-3-carbinol (I3C). Diindolylmethane (DIM) is a dimer of I3C that is formed under acidic conditions and unlike I3C is more stable with higher anti-cancer effects. In the present report, we demonstrate that DIM is a potent anti-proliferative agent compared to I3C in the hormone independent DU 145 CaP cells. The anti-prostate cancer effect is mediated by the inhibition of the Akt signal transduction pathway as DIM, in sharp contrast to I3C, induces the downregulation of Akt, p-Akt, and PI3 kinase. DIM also induced a G1 arrest in DU 145 cells by flow cytometry and downstream concurrent inhibition of cell cycle parameters such as cyclin D1, cdk4, and cdk6. Our data suggest a need for further development of DIM, as a chemopreventive agent for CaP, which justifies epidemiological evidences and molecular targets that are determinants for CaP dissemination/progression. The ingestion of DIM may benefit CaP patients and reduce disease recurrence by eliminating micro-metastases that may be present in patients who undergo radical prostatectomy

Prevention of breast cancer.

Science.gov (United States)

Olver, Ian N

2016-11-21

Modifiable lifestyle factors may reduce the risk of developing breast cancer. Obesity is associated particularly with post-menopausal breast cancer. Diet is important, and exercise equivalent to running for up to 8 hours each week reduces the risk of breast cancer, both in its own right and through reducing obesity. Alcohol consumption may be responsible for 5.8% of breast cancers in Australia and it is recommended to reduce this to two standard drinks per day. Drinking alcohol and smoking increases the risk for breast cancer and, therefore, it is important to quit tobacco smoking. Prolonged use of combined oestrogen and progesterone hormone replacement therapy and oral contraceptives may increase breast cancer risk and this must be factored into individual decisions about their use. Ionising radiation, either from diagnostic or therapeutic radiation or through occupational exposure, is associated with a high incidence of breast cancer and exposure may be reduced in some cases. Tamoxifen chemoprevention may reduce the incidence of oestrogen receptor positive cancer in 51% of women with high risk of breast cancer. Uncommon but serious side effects include thromboembolism and uterine cancer. Raloxifene, which can also reduce osteoporosis, can be used in post-menopausal women and is not associated with the development of uterine cancer. Surgical prophylaxis with bilateral mastectomy and salpingo-oophorectomy can reduce the risk of breast cancer in patients carrying BRCA1 or BRCA2 mutations. For preventive treatments, mammographic screening can identify other women at high risk.

Andrographolide, a diterpene lactone from Andrographis paniculata and its therapeutic promises in cancer.

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Islam, Muhammad Torequl; Ali, Eunüs S; Uddin, Shaikh Jamal; Islam, Md Amirul; Shaw, Subrata; Khan, Ishaq N; Saravi, Seyed Soheil Saeedi; Ahmad, Saheem; Rehman, Shahnawaz; Gupta, Vijai Kumar; Găman, Mihnea-Alexandru; Găman, Amelia Maria; Yele, Santosh; Das, Asish Kumar; de Castro E Sousa, João Marcelo; de Moura Dantas, Sandra Maria Mendes; Rolim, Hercília Maria Lins; de Carvalho Melo-Cavalcante, Ana Amélia; Mubarak, Mohammad S; Yarla, Nagendra Sastry; Shilpi, Jamil A; Mishra, Siddhartha Kumar; Atanasov, Atanas G; Kamal, Mohammad Amjad

2018-04-28

The diterpene lactone andrographolide, isolated from Andrographis paniculata, has been proven to possess several important protective biological activities, including antioxidant, anti-inflammatory, immunomodulatory, antiseptic, antimicrobial, cytotoxic, hypolipidemic, cardioprotective, hepatoprotective, and neuroprotective effects. In addition, it has been reported to play a therapeutic role in the treatment of major human diseases, such as Parkinson's disease, rheumatoid arthritis, and colitis. This systematic review aims to highlight andrographolide as a promising agent in cancer treatment. To this purpose, a number of databases were used to search for the cytotoxic/anticancer effects of andrographolide in pre-clinical and clinical studies. Among 1703 identified literature articles, 139 were included in this review; 109 were investigated as non-clinical, whereas 24, 3, and 3 were pre-clinical, clinical, and non-pre-clinical trials, respectively. Among the model systems, cultured cell lines appeared as the most frequently (79.14%) used, followed by in vivo models using rodents, among others. Furthermore, andrographolide was found to exert cytotoxic/anticancer effects on almost all types of cell lines with the underlying mechanisms involving oxidative stress, cell cycle arrest, anti-inflammatory and immune system mediated effects, apoptosis, necrosis, autophagy, inhibition of cell adhesion, proliferation, migration, invasion, anti-angiogenic activity, and other miscellaneous actions. After careful consideration of the relevant evidence, we suggest that andrographolide can be one of the potential agents in the treatment of cancer in the near future. Copyright © 2018 Elsevier B.V. All rights reserved.

Curcumin induces apoptosis-independent death in oesophageal cancer cells.

LENUS (Irish Health Repository)

O'Sullivan-Coyne, G

2012-01-31

BACKGROUND: Oesophageal cancer incidence is increasing and survival rates remain extremely poor. Natural agents with potential for chemoprevention include the phytochemical curcumin (diferuloylmethane). We have examined the effects of curcumin on a panel of oesophageal cancer cell lines. METHODS: MTT (3-(4,5-dimethyldiazol-2-yl)-2,5 diphenyl tetrazolium bromide) assays and propidium iodide staining were used to assess viability and DNA content, respectively. Mitotic catastrophe (MC), apoptosis and autophagy were defined by both morphological criteria and markers such as MPM-2, caspase 3 cleavage and monodansylcadaverine (MDC) staining. Cyclin B and poly-ubiquitinated proteins were assessed by western blotting. RESULTS: Curcumin treatment reduces viability of all cell lines within 24 h of treatment in a 5-50 muM range. Cytotoxicity is associated with accumulation in G2\\/M cell-cycle phases and distinct chromatin morphology, consistent with MC. Caspase-3 activation was detected in two out of four cell lines, but was a minor event. The addition of a caspase inhibitor zVAD had a marginal or no effect on cell viability, indicating predominance of a non-apoptotic form of cell death. In two cell lines, features of both MC and autophagy were apparent. Curcumin-responsive cells were found to accumulate poly-ubiquitinated proteins and cyclin B, consistent with a disturbance of the ubiquitin-proteasome system. This effect on a key cell-cycle checkpoint regulator may be responsible for the mitotic disturbances and consequent cytotoxicity of this drug. CONCLUSION: Curcumin can induce cell death by a mechanism that is not reliant on apoptosis induction, and thus represents a promising anticancer agent for prevention and treatment of oesophageal cancer.

Environmental Epigenetics: Crossroad between Public Health, Lifestyle, and Cancer Prevention

Science.gov (United States)

Romani, Massimo; Pistillo, Maria Pia; Banelli, Barbara

2015-01-01

Epigenetics provides the key to transform the genetic information into phenotype and because of its reversibility it is considered an ideal target for therapeutic interventions. This paper reviews the basic mechanisms of epigenetic control: DNA methylation, histone modifications, chromatin remodeling, and ncRNA expression and their role in disease development. We describe also the influence of the environment, lifestyle, nutritional habits, and the psychological influence on epigenetic marks and how these factors are related to cancer and other diseases development. Finally we discuss the potential use of natural epigenetic modifiers in the chemoprevention of cancer to link together public health, environment, and lifestyle. PMID:26339624

A novel NSAID derivative, phospho-ibuprofen, prevents AOM-induced colon cancer in rats

Science.gov (United States)

OUYANG, NENGTAI; JI, PING; WILLIAMS, JENNIE L.

2013-01-01

The cancer chemopreventive properties and gastrointestinal toxicity of ibuprofen are well documented. Modification of existing NSAIDs has improved on the chemopreventive efficacy of this agent and reduced its toxicity. In this study, ibuprofen and a modified derivative (phospho-modified ibuprofen or p-ibuprofen) were used in a chemically induced model of colon cancer. Fisher 344 rats were injected with azoxymethane then treated with either ibuprofen (500 ppm) or p-ibuprofen (900 ppm) for 20 weeks to observe aberrant crypt foci (ACF) or 40 weeks to evaluate tumor incidence and multiplicity. β-catenin and p65 were measured in colonic tissues by immunofluorescence staining. Equal molar doses of ibuprofen (75 and 670 mg/kg) and p-ibuprofen (135 and 1,215 mg/kg) were administered to rats for 7 days to assess acute toxicity. The in vitro effect of p-ibuprofen on COX-2 and PGE2 synthesis, β-catenin expression and NF-κB activity were examined in RAW 264.7 macrophage and HCT 116 colon cancer cells. At week 20, p-ibuprofen and ibuprofen significantly reduced the multiplicity of ACF compared with control (pibuprofen and ibuprofen reduced the multiplicity of colon tumors compared with control (pibuprofen (670 mg/kg) and p-ibuprofen (1,215 mg/kg) resulted in stomach ulceration in 85.7% (6 out of 7) and 14.3% (1 out of 7) of rats, respectively, with pibuprofen and p-ibuprofen suppressed β-catenin nuclear translocation in colon cancer cells. In addition, p-ibuprofen but not ibuprofen inhibited NF-κB activation in colon cancer cells. Collectively, these results suggest that p-ibuprofen is a potential effective novel drug for long-term use in colon cancer prevention. PMID:23291777

Isoliquiritigenin, a flavonoid from licorice, blocks M2 macrophage polarization in colitis-associated tumorigenesis through downregulating PGE{sub 2} and IL-6

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Zhao, Haixia [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Zhang, Xinhua [Department of Liver, Biliary And Pancreatic Tumors, Hubei Cancer Hospital, Wuhan 430079 (China); Chen, Xuewei; Li, Ying; Ke, Zunqiong [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Tang, Tian [Department of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060 (China); Chai, Hongyan [Center for Gene Diagnosis, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Guo, Austin M. [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Department of Pharmacology, New York Medical College, Valhalla, NY 10595 (United States); Chen, Honglei, E-mail: hl-chen@whu.edu.cn [Department of Pathology and Pathophysiology, School of Medicine, Wuhan University, Wuhan 430071 (China); Yang, Jing, E-mail: yangjingliu2013@163.com [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China)

2014-09-15

M2 macrophage polarization is implicated in colorectal cancer development. Isoliquiritigenin (ISL), a flavonoid from licorice, has been reported to prevent azoxymethane (AOM) induced colon carcinogenesis in animal models. Here, in a mouse model of colitis-associated tumorigenesis induced by AOM/dextran sodium sulfate (DSS), we investigated the chemopreventive effects of ISL and its mechanisms of action. Mice were treated with AOM/DSS and randomized to receive either vehicle or ISL (3, 15 and 75 mg/kg). Tumor load, histology, immunohistochemistry, and gene and protein expressions were determined. Intragastric administration of ISL for 12 weeks significantly decreased colon cancer incidence, multiplicity and tumor size by 60%, 55.4% and 42.6%, respectively. Moreover, ISL inhibited M2 macrophage polarization. Such changes were accompanied by downregulation of PGE{sub 2} and IL-6 signaling. Importantly, depletion of macrophages by clodronate (Clod) or zoledronic acid (ZA) reversed the effects of ISL. In parallel, in vitro studies also demonstrated that ISL limited the M2 polarization of RAW264.7 cells and mouse peritoneal macrophages with concomitant inactivation of PGE{sub 2}/PPARδ and IL-6/STAT3 signaling. Conversely, exogenous addition of PGE{sub 2} or IL-6, or overexpression of constitutively active STAT3 reversed ISL-mediated inhibition of M2 macrophage polarization. In summary, dietary flavonoid ISL effectively inhibits colitis-associated tumorigenesis through hampering M2 macrophage polarization mediated by the interplay between PGE{sub 2} and IL-6. Thus, inhibition of M2 macrophage polarization is likely to represent a promising strategy for chemoprevention of colorectal cancer. - Highlights: • Isoliquiritigenin (ISL) prevents colitis-associated tumorigenesis. • ISL inhibits M2 macrophage polarization in vivo and in vitro. • ISL inhibits PGE{sub 2} and IL-6 signaling in colitis-associated tumorigenesis. • ISL may be an attractive candidate agent for

Use of antidepressants and risk of epithelial ovarian cancer

DEFF Research Database (Denmark)

Mørch, Lina S; Dehlendorff, Christian; Baandrup, Louise

2017-01-01

antidepressants, selective serotonin reuptake inhibitors, other antidepressants, and potential confounder drugs), medical and reproductive history and socioeconomic parameters, were obtained from nationwide registries. We used conditional logistic regression models to estimate adjusted odds ratios (ORs) and two.......80 (95% CI, 0.60-1.08). Among postmenopausal women, the inverse association was restricted to users of menopausal hormone therapy. In conclusion, use of selective serotonin reuptake inhibitors was associated with a decreased risk of epithelial ovarian cancer; thereby implying potential chemopreventive...

Encapsulated nanoepigallocatechin-3-gallate and elemental selenium nanoparticles as paradigms for nanochemoprevention

Directory of Open Access Journals (Sweden)

Wang D

2012-03-01

Full Text Available Dongxu Wang1, Ethan Will Taylor2, Yijun Wang1, Xiaochun Wan1, Jinsong Zhang11Key Laboratory of Tea Biochemistry and Biotechnology, School of Tea and Food Science, Anhui Agricultural University, Hefei, Anhui, People’s Republic of China; 2Department of Nanoscience, Joint School of Nanoscience and Nanoengineering, University of North Carolina at Greensboro, Greensboro, NC, USAAbstract: Chemoprevention that impedes one or more steps in carcinogenesis, via long-term administration of naturally occurring or synthetic compounds, is widely considered to be a crucial strategy for cancer control. Selenium (Se has chemopreventive effects, but its application is limited due to a low therapeutic index as shown in numerous animal experiments. In contrast to Se, which was known for its toxicity prior to the discovery of its beneficial effects, the natural compound epigallocatechin-3-gallate (EGCG was originally considered to be nontoxic. Due to its preventive effects on many types of cancer in various animal models, EGCG has been regarded as a prime example of a promising chemopreventive agent without major toxicity concerns. However, very recently, evidence has accumulated showing that efficacious doses of EGCG used in health promotion may not be far from its toxic dose level. Therefore, both Se and EGCG need to be modified by novel pharmaceutical technologies to attain enhanced efficacy and/or reduced toxicity. Nanotechnology may be one of these technologies. In support of this hypothesis, the characteristics of polylactic acid and polyethylene glycol-encapsulated nano-EGCG and elemental Se nanoparticles dispersed by bovine serum albumin are reviewed in this article. Encapsulation of EGCG to form nano-EGCG leads to its enhanced stability in plasma and remarkably superior chemopreventive effects, with more than tenfold dose advantages in inducing apoptosis and inhibition of both angiogenesis and tumor growth. Se at nanoparticle size (“Nano-Se”, compared

Potential Targets for Colorectal Cancer Prevention

Directory of Open Access Journals (Sweden)

Ali Shamseddine

2013-08-01

Full Text Available The step-wise development of colorectal neoplasia from adenoma to carcinoma suggests that specific interventions could delay or prevent the development of invasive cancer. Several key factors involved in colorectal cancer pathogenesis have already been identified including cyclooxygenase 2 (COX-2, nuclear factor kappa B (NF-κB, survivin and insulin-like growth factor-I (IGF-I. Clinical trials of COX-2 inhibitors have provided the “proof of principle” that inhibition of this enzyme can prevent the formation of colonic adenomas and potentially carcinomas, however concerns regarding the potential toxicity of these drugs have limited their use as a chemopreventative strategy. Curcumin, resveratrol and quercetin are chemopreventive agents that are able to suppress multiple signaling pathways involved in carcinogenesis and hence are attractive candidates for further research.

Role of GSK-3β in Regulation of Canonical Wnt/β-catenin Signaling and PI3-K/Akt Oncogenic Pathway in Colon Cancer.

Science.gov (United States)

Jain, Shelly; Ghanghas, Preety; Rana, Chandan; Sanyal, S N

2017-08-09

Non-steroidal anti-inflammatory drugs (NSAIDs) are emerging as novel chemopreventive agents because of their ability in blocking cellular proliferation, and thereby tumor development, and also by promoting apoptosis. GSK-3β, a serine threonine kinase and a negative regulator of the oncogenic Wnt/β-catenin signaling pathway, plays a critical role in the regulation of oncogenesis. Celecoxib and etoricoxib, the two cyclooxygenase-2 (COX-2) selective NSAIDs, and Diclofenac, a preferential COX-2 inhibitory NSAID, had shown uniformly the chemopreventive and anti-neoplastic effects in the early stage of colon cancer by promoting apoptosis as well as an over-expression of GSK-3β while down-regulating the PI3-K/Akt oncogenic pathway.

Inhibitory effect of Epstein-Barr virus activation by Citrus fruits, a cancer chemopreventor.

Science.gov (United States)

Iwase, Y; Takemura, Y; Ju-ichi, M; Kawaii, S; Yano, M; Okuda, Y; Mukainaka, T; Tsuruta, A; Okuda, M; Takayasu, J; Tokuda, H; Nishino, H

1999-05-24

To search useful compounds in Citrus fruit for cancer chemoprevention, we carried out a primary screening of extracts of fruit peels and seeds from 78 species of the genus Citrus and those from two Fortunella and one Poncirus species, which were closely related to the genus Citrus. These Citrus extracts inhibited the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) as a useful screening method for anti-tumor promoters. Our results indicated that Citrus containing substances may be inhibit susceptibility factors involved in the events leading to the development of cancer.

Insulin-Sensitizers, Polycystic Ovary Syndrome and Gynaecological Cancer Risk

Science.gov (United States)

Lauretta, Rosa; Lanzolla, Giulia; Vici, Patrizia; Mariani, Luciano; Moretti, Costanzo

2016-01-01

Preclinical, early phase clinical trials and epidemiological evidence support the potential role of insulin-sensitizers in cancer prevention and treatment. Insulin-sensitizers improve the metabolic and hormonal profile in PCOS patients and may also act as anticancer agents, especially in cancers associated with hyperinsulinemia and oestrogen dependent cancers. Several lines of evidence support the protection against cancer exerted by dietary inositol, in particular inositol hexaphosphate. Metformin, thiazolidinediones, and myoinositol postreceptor signaling may exhibit direct inhibitory effects on cancer cell growth. AMPK, the main molecular target of metformin, is emerging as a target for cancer prevention and treatment. PCOS may be correlated to an increased risk for developing ovarian and endometrial cancer (up to threefold). Several studies have demonstrated an increase in mortality rate from ovarian cancer among overweight/obese PCOS women compared with normal weight women. Long-term use of metformin has been associated with lower rates of ovarian cancer. Considering the evidence supporting a higher risk of gynaecological cancer in PCOS women, we discuss the potential use of insulin-sensitizers as a potential tool for chemoprevention, hypothesizing a possible rationale through which insulin-sensitizers may inhibit tumourigenesis. PMID:27725832

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. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemical Probes of Rapid Estrogen Signaling in Breast Cancer Treatment and Chemoprevention

National Research Council Canada - National Science Library

Weatherman, Rose V

2007-01-01

The goal of this project was to design new chemical tools to selectively probe the molecular mechanisms of action of rapid estrogen receptor action and their relevance to breast cancer drugs like tamoxifen...

Oral Field Cancerization: A Review

Directory of Open Access Journals (Sweden)

Raviraj Jayam

2010-01-01

Full Text Available The concept of oral field cancerization (OFC has been ever changing since its first description by Slaughter et al in 1953. The concept of OFC explains the mechanisms by which second primary tumors (OPTs develop- OPTs are the tumor-, which develop in the oral cavity in succession to the primary malignant tumors, which might vary in duration ranging from few months to years. The "classical" mechanism, which was originally observed by Slaughter describes that in the individuals with adverse habits, large areas of the aerodigestive tissue are affected by long-term exposure to carcinogens. In this preconditioned epithelium, multifocal carcinomas can develop as a result of independent mutations, and thus would not be genetically related. Although this mechanism was accepted for a quite a long time, the controversies began with the advent of new mechanism called the "clonal theory-, which explains that a single cell, on exposure to carcinogens, is transformed and give- rise to one large extended premalignant field by clonal expansion and gradual replacement of normal mucosa. In this field of various subclones, two separate tumors can develop after accumulation of additional genetic alteration-. Both tumors have the same clonal origin, and would thus share at least one early genetic event, which occurred before the initial clonal expansion. Also, the molecular studies regarding OFC have been expanding exponentially since a few years. The need for chemoprevention and the management of OFC with its resultant effect of development of second primary tumors has been challenging till today. Hence, the article tries to explain the conflicting aspects of various mechanisms by which SPTs develop, the molecular techniques, chemoprevention and therapeutic implications for oral field cancerization.

Colon carcinogenesis: influence of Western diet-induced obesity and targeting stem cells using dietary bioactive compounds.

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Kasdagly, Maria; Radhakrishnan, Sridhar; Reddivari, Lavanya; Veeramachaneni, D N Rao; Vanamala, Jairam

2014-01-01

Colon cancer strikes more than 1 million people annually and is responsible for more than 500,000 cancer deaths worldwide. Recent evidence suggests that the majority of malignancies, including colon cancer are driven by cancer stem cells (CSCs) that are resistant to current chemotherapeutic approaches leading to cancer relapse. Wnt signaling plays a critical role in colon stem cell renewal and carcinogenesis. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), a Wnt target gene, and aldehyde dehydrogenase 1 B1 (ALDH1B1) are good markers for normal and malignant human colon stem cells. Diet contributes to 20% to 42% of all human cancers and 50% to 90% of colon cancer. Recent evidence shows that the Western diet has a causative link to colon cancer; however, mechanisms of action are not fully elucidated. Western diet-induced obesity elevates systemic insulin-like growth factor-1 and insulin levels, which could lead to elevated proliferation and suppressed apoptosis of CSCs through PI3K/AKT/Wnt pathway. Although conventional chemotherapy targets the PI3K/AKT pathways and can significantly reduce tumor size, it fails to eliminate CSCs and has serious side effects. Dietary bioactive compounds such as grape seed extract, curcumin, lycopene, and resveratrol have promising chemopreventive effects, without serious side effects on various types of cancers due to their direct and indirect actions on CSC self-renewal pathways such as the Wnt pathway. Understanding the role of CSCs in diet-induced colon cancer will aid in development of evidence-based dietary chemopreventive strategies and/or therapeutic agents targeting CSCs. Copyright © 2014 Elsevier Inc. All rights reserved.

The protective effect of some Thai plants and their bioactive compounds in UV light-induced skin carcinogenesis.

Science.gov (United States)

de Silva, Madhura B; Tencomnao, Tewin

2018-05-02

Skin cancer, represents a major public health concern. While the vast majority is non-melanoma skin cancers, melanomas are mostly responsible for mortality. Solar UVB radiation is mutagenic and carcinogenic. It is primarily responsible for both non-melanoma and melanoma skin cancers via excessive production of reactive oxygen species (ROS), which mediate changes in inflammation and immunity, and have been implicated in all three stages of skin cancer development. Due to their regulatory role in numerous functions of cells, signaling pathways are targets for chemoprevention. The current standards in melanoma therapy are targeted and combination therapies, which, albeit prolong survival responses, are still prone to development of drug resistance. To this extent, drugs of natural origin continue to spark great interest. Thailand has a rich biodiversity of indigenous flora, which have traditionally been used to treat a variety of pathologies. The active components in plant extracts that have medicinal properties, termed 'bioactive compounds,' are efficient chemopreventive agents due to their antioxidant, antimutagenic, anticarcinogenic, and carcinogen detoxification properties. Thai plants and their bioactive compounds have shown protective effects on UV light-induced skin cancer in different experimental models. This warrants further in vivo investigations and translation to clinical studies to determine efficacy and safety, for use as lead compounds in targeted/combination therapy or adjuvant therapy with existing regimes. Coupled with a strategy for prevention, this offers a promising outlook for protection against photocarcinogenesis. Copyright © 2018 Elsevier B.V. All rights reserved.

Development of in vitro models for cellular and molecular studies in toxicology and chemoprevention

Energy Technology Data Exchange (ETDEWEB)

Mace, K.; Offord, E.A.; Harris, C.C.; Pfeifer, A.M.A. [Nestle Research Center, Lausanne (Switzerland)

1998-12-31

Many natural dietary phytochemicals found compounds found in fruits, vegetables, spices and tea have been shown in recent years to be protective against cancer in various animal models. In the light of the potential impact of these compounds on human health it is important to elucidate the mechanisms involved. We therefore developed and characterized relevant in vitro models using immortalized human epithelial cell lines derived from target tissues in carcinogenesis, such as lung, liver and colon. Assays were established, allowing the evaluation of the cytotoxic and genotoxic effects of various procarcinogens, including nitrosamines, mycotoxins and heterocyclic amines on these metabolically-competent human epithelial cell lines. These cellular models appeared to be a useful tool to study the capacity of certain food components to block the initiation stage of carcinogenesis. The ability of carnosol and carnosic acid from rosemary as well as the synthetic dithiolethione, oltipraz, to block the formation of DNA adducts, and their effects on the expression of phase I and phase II enzymes was investigated. We have observed that both rosemary extracts and oltiprax inhibited benzo(a)pyrene- or aflatoxin B{sub 1}-induced DNA adduct formation by strongly inhibiting CYP{sub 450} activities and inducing the expression of glutathione S-transferase. These results in human cell models give some insight into the different mechanisms involved in the chemopreventive action of both natural and synthetic compounds in relation to phase I and phase II enzymes. (orig.)

Nanoparticle Delivery of Natural Products in the Prevention and Treatment of Cancers: Current Status and Future Prospects

Energy Technology Data Exchange (ETDEWEB)

Bharali, Dhruba J. [The Pharmaceutical Research Institute at Albany College of Pharmacy and Health Sciences, 1 Discovery Drive, Rensselaer, NY 12144 (United States); Siddiqui, Imtiaz A.; Adhami, Vaqar M.; Chamcheu, Jean Christopher [Department of Dermatology, University of Wisconsin, Madison, WI 53706 (United States); Aldahmash, Abdullah M. [Stem Cell Unit, College of Medicine, King Saud University, Riyadh, 11461 (Saudi Arabia); University Hospital of Odense & Medical Biotechnology Center, Winslowsparken 25, DK-5000, Odense (Denmark); Mukhtar, Hasan [Department of Dermatology, University of Wisconsin, Madison, WI 53706 (United States); Mousa, Shaker A., E-mail: shaker.mousa@acphs.edu [The Pharmaceutical Research Institute at Albany College of Pharmacy and Health Sciences, 1 Discovery Drive, Rensselaer, NY 12144 (United States); Stem Cell Unit, College of Medicine, King Saud University, Riyadh, 11461 (Saudi Arabia)

2011-10-26

The advent of nanotechnology has had a revolutionary impact on many aspects of 21{sup st} century life. Nanotechnology has provided an opportunity to explore new avenues that conventional technologies have been unable to make an impact on for diagnosis, prevention, and therapy of different diseases, and of cancer in particular. Entities in nanometer sizes are excellent platforms to incorporate various drugs or active materials that can be delivered effectively to the desired action site without compromising the activity of the incorporated drug or material. In particular, nanotechnology entities can be used to deliver conventional natural products that have poor solubility or a short half life. Conventional natural products used with entities in nanometer sizes enable us to solve many of the inherent problems (stability, solubility, toxicity) associated with natural products, and also provide a platform for targeted delivery to tumor sites. We recently introduced the novel concept of using nanotechnology for enhancing the outcome of chemoprevention, which we called ‘nanochemoprevention’. This idea was subsequently exploited by several laboratories worldwide and has now become an advancing field in chemoprevention research. This review examines some of the applications of nanotechnology for cancer prevention and therapy using natural products.

Nanoparticle Delivery of Natural Products in the Prevention and Treatment of Cancers: Current Status and Future Prospects

International Nuclear Information System (INIS)

Bharali, Dhruba J.; Siddiqui, Imtiaz A.; Adhami, Vaqar M.; Chamcheu, Jean Christopher; Aldahmash, Abdullah M.; Mukhtar, Hasan; Mousa, Shaker A.

2011-01-01

The advent of nanotechnology has had a revolutionary impact on many aspects of 21 st century life. Nanotechnology has provided an opportunity to explore new avenues that conventional technologies have been unable to make an impact on for diagnosis, prevention, and therapy of different diseases, and of cancer in particular. Entities in nanometer sizes are excellent platforms to incorporate various drugs or active materials that can be delivered effectively to the desired action site without compromising the activity of the incorporated drug or material. In particular, nanotechnology entities can be used to deliver conventional natural products that have poor solubility or a short half life. Conventional natural products used with entities in nanometer sizes enable us to solve many of the inherent problems (stability, solubility, toxicity) associated with natural products, and also provide a platform for targeted delivery to tumor sites. We recently introduced the novel concept of using nanotechnology for enhancing the outcome of chemoprevention, which we called ‘nanochemoprevention’. This idea was subsequently exploited by several laboratories worldwide and has now become an advancing field in chemoprevention research. This review examines some of the applications of nanotechnology for cancer prevention and therapy using natural products

Role of pomegranate and citrus fruit juices in colon cancer prevention

Science.gov (United States)

Jaganathan, Saravana Kumar; Vellayappan, Muthu Vignesh; Narasimhan, Gayathri; Supriyanto, Eko

2014-01-01

Colorectal cancer is the second leading cause of cancer-related deaths in the United States. Recent studies prove that though chemotherapeutic agents are being used for the treatment of colon cancer, they become non-effective when the cancer progresses to an invasive stage. Since consumption of certain dietary agents has been linked with various cancers, fruit juices have been investigated for their consistently protective effect against colon cancer. The unique biochemical composition of fruit juices is responsible for their anticancer properties. In this review, the chemo-preventive effect of fruit juices such as pomegranate and citrus juices against colon cancer are discussed. For this purpose, the bioavailability, in vitro and in vivo effects of these fruit juices on colorectal cancer are highlighted. Moreover, there is a scarcity of studies involving human trials to estimate the preventive nature of these juices against colon cancer. This review will support the need for more preclinical tests with these crude juices and their constituents in different colorectal cancer cell lines and also some epidemiological studies in order to have a better understanding and promote pomegranate and citrus juices as crusaders against colon cancer. PMID:24782614

Combined ginger extract & Gelam honey modulate Ras/ERK and PI3K/AKT pathway genes in colon cancer HT29 cells.

Science.gov (United States)

Tahir, Analhuda Abdullah; Sani, Nur Fathiah Abdul; Murad, Noor Azian; Makpol, Suzana; Ngah, Wan Zurinah Wan; Yusof, Yasmin Anum Mohd

2015-04-01

The interconnected Ras/ERK and PI3K/AKT pathways play a central role in colorectal tumorigenesis, and they are targets for elucidating mechanisms involved in attempts to induce colon cancer cell death. Both ginger (Zingiber officinale) and honey have been shown to exhibit anti-tumor and anti-inflammation properties against many types of cancer, including colorectal cancer. However, there are currently no reports showing the combined effect of these two dietary compounds in cancer growth inhibition. The aim of this study was to evaluate the synergistic effect of crude ginger extract and Gelam honey in combination as potential cancer chemopreventive agents against the colorectal cancer cell line HT29. The cells were divided into 4 groups: the first group represents HT29 cells without treatment, the second and third groups were cells treated singly with either ginger or Gelam honey, respectively, and the last group represents cells treated with ginger and Gelam honey combined. The results of MTS assay showed that the IC50 of ginger and Gelam honey alone were 5.2 mg/ml and 80 mg/ml, respectively, whereas the IC50 of the combination treatment was 3 mg/ml of ginger plus 27 mg/ml of Gelam honey with a combination index of ginger and Gelam honey treatment was associated with the stimulation of early apoptosis (upregulation of caspase 9 and IκB genes) accompanied by downregulation of the KRAS, ERK, AKT, Bcl-xL, NFkB (p65) genes in a synergistic manner. In conclusion, the combination of ginger and Gelam honey may be an effective chemopreventive and therapeutic strategy for inducing the death of colon cancer cells.

Phytochemicals in Skin Cancer Prevention and Treatment: An Updated Review

Directory of Open Access Journals (Sweden)

Chau Yee Ng

2018-03-01

Full Text Available Skin is the largest human organ, our protection against various environmental assaults and noxious agents. Accumulation of these stress events may lead to the formation of skin cancers, including both melanoma and non-melanoma skin cancers. Although modern targeted therapies have ameliorated the management of cutaneous malignancies, a safer, more affordable, and more effective strategy for chemoprevention and treatment is clearly needed for the improvement of skin cancer care. Phytochemicals are biologically active compounds derived from plants and herbal products. These agents appear to be beneficial in the battle against cancer as they exert anti-carcinogenic effects and are widely available, highly tolerated, and cost-effective. Evidence has indicated that the anti-carcinogenic properties of phytochemicals are due to their anti-oxidative, anti-inflammatory, anti-proliferative, and anti-angiogenic effects. In this review, we discuss the preventive potential, therapeutic effects, bioavailability, and structure–activity relationship of these selected phytochemicals for the management of skin cancers. The knowledge compiled here will provide clues for future investigations on novel oncostatic phytochemicals and additional anti-skin cancer mechanisms.

Conjugated linoleic acid ameliorates inflammation-induced colorectal cancer in mice through activation of PPARgamma.

Science.gov (United States)

Evans, Nicholas P; Misyak, Sarah A; Schmelz, Eva M; Guri, Amir J; Hontecillas, Raquel; Bassaganya-Riera, Josep

2010-03-01

Conjugated linoleic acid (CLA) exerts a protective effect on experimental inflammatory bowel disease and shows promise as a chemopreventive agent against colorectal cancer (CRC) in mice, although the mechanisms by which it exerts its beneficial effects against malignancies in the gut are not completely understood. Mice lacking PPARgamma in immune and epithelial cells and PPARgamma-expressing littermates were fed either control or CLA-supplemented (1 g CLA/100 g) diets to determine the role of PPARgamma in inflammation-induced CRC. To induce tumor formation and colitis, mice were treated with azoxymethane and then challenged with 2% dextran sodium sulfate, respectively. Dietary CLA ameliorated disease activity, decreased colitis, and prevented adenocarcinoma formation in the PPARgamma-expressing floxed mice but not in the tissue-specific PPARgamma-null mice. Dietary CLA supplementation significantly decreased the percentages of macrophages in the mesenteric lymph nodes (MLN) regardless of the genotype and increased regulatory T cell numbers in MLN of PPARgamma-expressing, but not in the tissue-specific, PPARgamma-null mice. Colonic tumor necrosis factor-alpha mRNA expression was significantly suppressed in CLA-fed, PPARgamma-expressing mice. This study suggests CLA ameliorates colitis and prevents tumor formation in part through a PPARgamma-dependent mechanism.

Activation and Molecular Targets of Peroxisome Proliferator-Activated Receptor-γ Ligands in Lung Cancer

Directory of Open Access Journals (Sweden)

Raphael A. Nemenoff

2008-01-01

Full Text Available Lung cancer is the leading cause of cancer death, and five-year survival remains poor, raising the urgency for new treatment strategies. Activation of PPARγ represents a potential target for both the treatment and prevention of lung cancer. Numerous studies have examined the effect of thiazolidinediones such as rosiglitazone and pioglitazone on lung cancer cells in vitro and in xenograft models. These studies indicate that activation of PPARγ inhibits cancer cell proliferation as well as invasiveness and metastasis. While activation of PPARγ can occur by direct binding of pharmacological ligands to the molecule, emerging data indicate that PPARγ activation can occur through engagement of other signal transduction pathways, including Wnt signaling and prostaglandin production. Data, both from preclinical models and retrospective clinical studies, indicate that activation of PPARγ may represent an attractive chemopreventive strategy. This article reviews the existing biological and mechanistic experiments focusing on the role of PPARγ in lung cancer, focusing specifically on nonsmall cell lung cancer.

Does folic-acid supplementation prevent or promote colorectal cancer? Results from model-based predictions

OpenAIRE

Luebeck, EG; Moolgavkar, SH; Liu, AY; Boynton, A; Ulrich, CM

2008-01-01

Folate is essential for nucleotide synthesis, DNA-replication and methyl-group supply. Low-folate status has been associated with increased risks of several cancer types, suggesting a chemopreventive role of folate. However, recent findings on giving folic acid (FA) to patients with a history of colorectal polyps raise concerns about the efficacy and safety of folate supplementation and the long-term health effects of folate fortification. Results suggest that undetected precursor lesions may...

Gastric cancer: epidemiology, prevention, classification, and treatment

Directory of Open Access Journals (Sweden)

Sitarz R

2018-02-01

Full Text Available Robert Sitarz,1–3 Małgorzata Skierucha,1,2 Jerzy Mielko,1 G Johan A Offerhaus,3 Ryszard Maciejewski,2 Wojciech P Polkowski1 1Department of Surgical Oncology, Medical University of Lublin, Lublin, Poland; 2Department of Human Anatomy, Medical University of Lublin, Lublin, Poland; 3Department of Pathology, University Medical Centre, Utrecht, The Netherlands Abstract: Gastric cancer is the second most common cause of cancer-related deaths in the world, the epidemiology of which has changed within last decades. A trend of steady decline in gastric cancer incidence rates is the effect of the increased standards of hygiene, conscious nutrition, and Helicobacter pylori eradication, which together constitute primary prevention. Avoidance of gastric cancer remains a priority. However, patients with higher risk should be screened for early detection and chemoprevention. Surgical resection enhanced by standardized lymphadenectomy remains the gold standard in gastric cancer therapy. This review briefly summarizes the most important aspects of gastric cancers, which include epidemiology, risk factors, classification, diagnosis, prevention, and treatment. The paper is mostly addressed to physicians who are interested in updating the state of art concerning gastric carcinoma from easily accessible and credible source. Keywords: gastric cancer, epidemiology, classification, risk factors, treatment

Phytochemicals from cruciferous vegetables, epigenetics, and prostate cancer prevention.

Science.gov (United States)

W Watson, Gregory; M Beaver, Laura; E Williams, David; H Dashwood, Roderick; Ho, Emily

2013-10-01

Epidemiological evidence has demonstrated a reduced risk of prostate cancer associated with cruciferous vegetable intake. Follow-up studies have attributed this protective activity to the metabolic products of glucosinolates, a class of secondary metabolites produced by crucifers. The metabolic products of glucoraphanin and glucobrassicin, sulforaphane, and indole-3-carbinol respectively, have been the subject of intense investigation by cancer researchers. Sulforaphane and indole-3-carbinol inhibit prostate cancer by both blocking initiation and suppressing prostate cancer progression in vitro and in vivo. Research has largely focused on the anti-initiation and cytoprotective effects of sulforaphane and indole-3-carbinol through induction of phases I and II detoxification pathways. With regards to suppressive activity, research has focused on the ability of sulforaphane and indole-3-carbinol to antagonize cell signaling pathways known to be dysregulated in prostate cancer. Recent investigations have characterized the ability of sulforaphane and indole-3-carbinol derivatives to modulate the activity of enzymes controlling the epigenetic status of prostate cancer cells. In this review, we will summarize the well-established, "classic" non-epigenetic targets of sulforaphane and indole-3-carbinol, and highlight more recent evidence supporting these phytochemicals as epigenetic modulators for prostate cancer chemoprevention.