Department of Otolaryngology, Ajou University School of Medicine, Suwon, Korea
In the era of personalized medicine, selecting the ideal treatment modality for head and neck cancer is becoming more complex. Also, despite the use of the newest agents, overall survival has not been improved notably over the past few decades. Currently, in accordance with the development of diagnostic tools, prevention and early detection of cancer are being emphasized more in obtaining better treatment outcomes. Among the various cancer preventative methods, the use of green tea is one of the most common approaches, and tea is known to be involved in multiple steps of carcinogenesis. Thus, in this short review, the protective roles of green tea components against the initiation, progression, and metastasis of head and neck malignancies will be discussed. Conclusion ... green tea component, EGCG, may be the single most important agent, which has demonstrated positive effects in preventing and treating head and neck cancers. EGCC protects against diverse steps in cancer progression and invasion through multiple and complex signal transduction pathways.....
1Tang Center for Herbal Medicine Research, The Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, U.S.A.
2Department of Anesthesia and Critical Care, The Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, U.S.A.
3Department of Pathology, The Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, U.S.A.
4Department of Surgery, The Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, U.S.A.
5Ben May Department for Cancer Research, The Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, U.S.A.
6Committee on Clinical Pharmacology and Pharmacogenomics, The Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, U.S.A.
Abstract Background: Former studies have shown that extract from American ginseng (Panax quinquefolius) may possess certain antiproliferative effects on cancer cells. In this study, the chemical constituents of both untreated and heat-processed American ginseng and their antiproliferative activities on human breast cancer cells were evaluated. Materials and Methods: American ginseng roots were steamed at 120°C for 1 h or 2 h. The major ginsenosides in the two steamed and in the unsteamed extracts were quantitatively determined using high performance liquid chromatography (HPLC). The antiproliferative activities of these extracts and individual ginsenosides on MCF-7 and MDA-MB-231 breast cancer cells were assayed using the MTS method. The effects of the extracts and the ginsenosides on the induction of cell apoptosis, the expression of cyclins A and D1, and cell cycle arrest were evaluated. Results: Compared to the untreated extract, heat-processing reduced the content of ginsenosides Rb1, Re, Rc and Rd, and increased the content of Rg2 and Rg3. After 2 h steaming, the percent content of ginsenoside Rg3 was increased from 0.06% to 5.9% . Compared to the unsteamed extract, the 2 h steamed extract significantly increased the antiproliferative activity and significantly reduced the number of viable cells. The steamed extract also significantly reduced the expression of cyclin A and cyclin D1. The cell cycle assay showed that the steamed extract and ginsenoside Rg3 arrested cancer cells in G1-phase. Conclusion: Heat-processing of American ginseng root significantly increases antiproliferative activity and influences the cell cycle profile.
of Epidemiology, Department of Family and Preventive Medicine,
University of California San Diego, La Jolla CA, U.S.A.
2Naval Health Research Center, San Diego, CA, U.S.A.
of Epidemiology and Biostatistics, Graduate School of Public Health,
San Diego State University, San Diego CA,
of Surgery, School of Medicine, University of California San Diego, La
Jolla CA, U.S.A.
Low serum levels of 25-hydroxyvitamin D [25(OH)D] have been
associated with a high risk of breast cancer. Since
publication of the most current meta-analysis of 25(OH)D and breast
cancer risk, two new nested case–control studies have
Materials and Methods: A PubMed search for all
case–control studies on risk of breast cancer by 25(OH)D concentration
identified 11 eligible studies. Data from all 11
studies were combined in order to calculate the pooled odds ratio of
the highest vs. lowest quantile of 25(OH)D across
Results: The overall Peto odds ratio summarizing
the estimated risk in the highest compared to the
lowest quantile across all 11 studies was 0.61 (95% confidence
interval 0.47, 0.80).
study supports the hypothesis that higher serum 25(OH)D levels reduce
the risk of breast cancer. According to the review
of observational studies, a serum 25(OH)D level of 47 ng/ml was
associated with a 50% lower risk of breast cancer.
Dietary Walnut Suppressed Mammary Gland Tumorigenesis in the C(3)1 TAg Mouse W. Elaine Hardmana, Gabriela Iona, Juliana A. Akinsetea & Theodore R. Wittea
Abstract Walnuts contain multiple ingredients that, individually, have been shown to slow cancer growth, including omega-3 fatty acids, antioxidants, and phytosterols. In previous research, consumption of walnuts has slowed the growth of implanted breast cancers. We wanted to determine whether regular walnut consumption might reduce the risk for developing cancer. Homozygous male C(3)1 TAg mice were bred with female SV129 mice consuming either the control AIN-76 diet or the walnut-containing diet. At weaning, the female hemizygous pups were randomized to control or walnut-containing diets and followed for tumor development. Compared to a diet without walnuts, consumption of walnuts significantly reduced tumor incidence (fraction of mice with at least one tumor), multiplicity (number of glands with tumor/mouse), and size. Gene expression analyses indicated that consumption of the walnut diet altered expression of multiple genes associated with proliferation and differentiation of mammary epithelial cells. A comparison with another dietary intervention indicated that the omega 3 content alone did not account for the extent of tumor suppression due to the walnut. The results of this study indicate that walnut consumption could contribute to a healthy diet to reduce risk for breast cancer.
Conclusion These data indicate that exposure to a small amount of walnut in the diet of this transgenic mouse slowed the development and reduced the multiplicity of mammary gland cancers but does not define the mechanism of action for the walnut nor an active ingredient of the walnut. Walnut in the diet was associated with alterations in cell signaling pathways involved in proliferation, cell differentiation, and apoptosis. The signaling pathways altered in mammary glands of these mice have been identified as important in the development of human breast cancer, thus this study should be relevant to humans. The fatty acid composition of the mammary glands was altered but comparison to another study with the same amount of omega 3 fatty acids in the diet indicates that increased omega 3 fatty acids in the mammary gland does not explain the altered tumor incidence. However, alterations in dietary gamma tocopherol were inversely associated with tumorigenesis.More work will need to be done to determine the components of walnut and the mechanisms associated with tumor suppression. However, humans eat the whole nut, not specific components. It seems likely that incorporation of walnuts as part of a healthy diet could reduce the risk for breast cancer in humans.
Green Tea and cancer Prevention Chung S. Yanga & Xin Wanga
Abstract Extracts of green tea and green tea polyphenols have exhibited inhibitory effects against the formation and development of tumors at different organ sites in animals. These include animal models for skin, lung, oral cavity, esophagus, stomach, intestine, colon, liver, pancreas, bladder, mammary gland, and prostate cancers. In addition to suppressing cell proliferation, promoting apoptosis, and modulating signaling transduction, green tea polyphenols, especially (-)-epigallocatechin-3-gallate, also inhibit cell invasion, angiogenesis, and metastasis. This article reviews data on the cancer preventive activities of green tea polyphenols, possible mechanisms involved, and the relationship between green tea consumption and human cancer risk.
Conclusion The inhibitory activities of tea and tea catechins against carcinogenesis have been demonstrated in different animal models. Studies in cell lines have also showed that tea catechins can affect a variety of signaling and metabolic pathways. These molecular events could result in cancer cell growth inhibition, apoptosis, and inhibition of invasion, angiogenesis, and metastasis. These activities and the prevention of carcinogenesis have been demonstrated in animal model, but the cancer preventive activity of tea has not been consistently observed in human studies. This may be due to the relatively lower levels of tea consumption by some human populations (than animal studies) and the various confounding factors in epidemiological studies in different populations. The low bioavailability of tea polyphenols, such as EGCG, is also an issue. For agents with low systematic bioavailability, their direct contact with the digestive tract could be important for their cancer preventive activity. This point should be applicable to the activities of EGCG and polyphenols in many other foods or beverages. This information, as well as the biological properties and activities of tea polyphenols reviewed here, may be useful in design of prospective studies and in the selection of the agent, dosage, and biomarkers for intervention trials. The results of such well-designed studies will provide more definitive information on the possible use of tea for the reduction of cancer risk in different populations.
Significance of Dietary Antioxidants in Averting Cancer Subrahmanyam V1* and Radhika P Ramachandran2*
1Department of Biochemistry, School of Life sciences, University of Hyderabad, Hyderabad 2Department of Biotechnology, Faculty of Engineering and Technology, SRM University, Chennai
Abstract Reactive oxygen species are constantly produced in our body due to various factors like environmental pollution, unhealthy diet habits, cellular metabolism etc. Epidemiological studies suggest that the intakes of antioxidants are inversely related to the cancer risk. While the cell culture studies confirm the effect of antioxidants against cancer, the clinical trials remains inconclusive. The human population is heterogeneous regarding Reactive oxygen species (ROS), so screening the human population for developing the risk of cancer will provide a scientific ground for the application of antioxidants. Research is increasingly showing that those who eat antioxidant-rich foods reap health benefits. Foods, rather than supplements, may boost antioxidant levels because foods contain an unmatchable array of antioxidant substances.
Conclusions By this we can conclude that dietary antioxidants can provide a wide sort of health benefits, caused by the in the presence of free radicals on key biomolecules like lipids or nucleic acids. We can also prevent the various diseases which are occurring in the presence of Reactive Oxygen Species (ROS) like cancer and oxidative stress related diseases.
Top Ranked Antioxidant foods : Small red beans, dried, Wild blueberries, Red kidney beans, dried, Pinto beans, Blueberries, cultivated, Cranberries, Artichoke hearts, cooked, Blackberries, Dried prunes, Raspberries, Strawberries, Red delicious apple, Granny Smith apple , Pecans, Sweet cherries, Black plum, Russet potato, cooked, Black beans, Plum, Gala apple.
The highest ranked foods in four major categories are as follows: Fruits: blueberries, cranberries, and blackberries. Vegetables: beans, artichoke hearts, and surprisingly, russet potatoes. Nuts: pecans, walnuts, and hazelnuts. Spices: cinnamon, oregano, and ground cloves.
Luteolin, a flavonoid with potentials for cancer prevention and therapy Yong Lin,1* Ranxin Shi,2# Xia Wang,1,3 and Han-Ming Shen2
1Molecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest DR., SE, Albuquerque, NM 87108, USA 2Department of Community, Occupational and Family Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Republic of Singapore 3Laboratory of Molecular and Translational Medicine, West China Second University Hospital, Sichuan University, Chengdu 610041, China
Abstract Luteolin, 3′,4′,5,7-tetrahydroxyflavone, is a common flavonoid that exists in many types of plants including fruits, vegetables, and medicinal herbs. Plants rich in luteolin have been used in Chinese traditional medicine for treating various diseases such as hypertension, inflammatory disorders, and cancer. Having multiple biological effects such as anti-inflammation, anti-allergy and anticancer, luteolin functions as either an antioxidant or a pro-oxidant biochemically. The biological effects of luteolin could be functionally related to each other. For instance, the anti-inflammatory activity may be linked to its anticancer property. Luteolin's anticancer property is associated with the induction of apoptosis, and inhibition of cell proliferation, metastasis and angiogenesis. Furthermore, luteolin sensitizes cancer cells to therapeutic-induced cytotoxicity through suppressing cell survival pathways such as phosphatidylinositol 3′-kinase (PI3K)/Akt, nuclear factor kappa B (NF-κB), and X-linked inhibitor of apoptosis protein (XIAP), and stimulating apoptosis pathways including those that induce the tumor suppressor p53. These observations suggest that luteolin could be an anticancer agent for various cancers. Furthermore, recent epidemiological studies have attributed a cancer prevention property to luteolin. In this review, we summarize the progress of recent research on luteolin, with a particular focus on its anticancer role and molecular mechanisms underlying this property of luteolin.
MicroRNA, Nutrition, and Cancer Prevention1 Sharon A. Ross* and Cindy D. Davis
Abstract MicroRNA (miRNA) are small noncoding RNA molecules that are involved in post-transcriptional gene silencing. Alterations in miRNA expression are observed in and may underlie many different human diseases, including cancer. In fact, miRNA have been shown to affect the hallmarks of cancer, including sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Genetic and epigenetic alterations may explain aberrant miRNA expression in cancer cells and may also contribute to cancer risk. It is now thought that by circulating through the bloodstream, miRNA can exert their effects at distant sites as well as within the cells of origin. Recent evidence suggests that nutrients and other bioactive food components protect against cancer through modulation of miRNA expression. Moreover, dietary factors have been shown to modify miRNA expression and their mRNA targets in various cancer processes, including apoptosis, cell cycle regulation, differentiation, inflammation, angiogenesis, and metastasis as well as pathways in stress response. Herein, we provide a brief overview of dietary modulation of miRNA expression and its potential role in cancer prevention. Understanding the affect of dietary factors on miRNA expression and function may provide insight on prevention strategies to reduce the burden of cancer.
Phytochemicals as Protectors Against Ultraviolet Radiation: Versatility of Effects and Mechanisms Albena T. Dinkova-Kostova1
1Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Scotland, UK and Department of Pharmacology and Molecular Sciences and Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
Abstract Ultraviolet (UV) radiation is one of the most abundant carcinogens in our environment, and the development of non-melanoma skin cancers, the most common type of human malignancy worldwide, represents one of the major consequences of excessive exposure. Because of growing concerns that the level of UV radiation is increasing as a result of depletion of the stratospheric ozone and climate change, the development of strategies for protection of the skin is an urgent need. Many phytochemicals that belong to various families of secondary metabolites, such as alkaloids (caffeine, sanguinarine), flavonoids [(−)-epigallocatechin 3-gallate, genistein, silibinin], carotenoids (β-carotene, lycopene), and isothiocyanates (sulforaphane), offer exciting platforms for the development of such protective strategies. These phytochemicals have been consumed by humans for many centuries as part of plant-rich diets and are presumed to be of low toxicity, an essential requirement for a chemoprotective agent. Mechanistically, they affect multiple signalling pathways and protect against UV radiation-inflicted damage by their ability to act as direct and indirect antioxidants, as well as anti-inflammatory and immunomodulatory agents. Such ”pluripotent character” is a critical prerequisite for an agent that is designed to counteract the multiple damaging effects of UV radiation. Especially attractive are inducers of the Keap1/Nrf2/ARE pathway, which controls the gene expression of proteins whose activation leads to enhanced protection against oxidants and electrophiles. Such protection is comprehensive, long-lasting, and unlikely to cause pro-oxidant effects or interfere with the synthesis of vitamin D.
Potential of Spice-Derived Phytochemicals for Cancer Prevention Bharat B. Aggarwal, Ajaikumar B. Kunnumakkara, Kuzhuvelil B. Harikumar, Sheeja T. Tharakan, Bokyung Sung,Preetha Anand
Affiliation Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA
Abstract Although spices have been used for thousands of years and are known for their flavor, taste and color in the food, they are not usually recognized for their medicinal value. Extensive research within the last two decades from our laboratory and others has indicated that there are phytochemicals present in spices thatmay prevent various chronic illnesses including cancerous, diabetic, cardiovascular, pulmonary, neurological and autoimmune diseases. For instance, the potential of turmeric (curcumin), red chilli (capsaicin), cloves (eugenol), ginger (zerumbone), fennel (anethole), kokum (gambogic acid), fenugreek (diosgenin), and black cumin (thymoquinone) in cancer prevention has been established. Additionally, the mechanism by which these agents mediate anticancer effects is also becoming increasingly evident. The current review describes the active components of some of the major spices, their mechanisms of action and their potential in cancer prevention.
Conclusion From the description provided above it is clear that spice-derived phytochemicals have an enormous potential in the prevention and treatment of cancer. They can induce apoptosis, suppress proliferation of tumor cells, inhibit invasion and angiogenesis, and prevent even bone loss. These phytochemicals mediate their effects through multiple targets and yet pharmacologically they are highly safe. More animal studies and clinical trials are needed to prove the usefulness of these agents. Safety, inexpensive cost, years of intake by humans and their efficacy make them ideal agents. Therefore it is not too surprising to note that Vasco de Gama tried to look for these spices almost five centuries ago.
Perspectives for Cancer Prevention With Natural Compounds
A.R.M. Ruhul Amin, Omer Kucuk, Fadlo R. Khuri, and Dong M. Shin From the Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA.Corresponding author: Dong M. Shin, MD, Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA 30322
Abstract Cancer is the second leading cause of death in the United States. Despite the estimated 565,650 deaths in 2008 of Americans as a result of cancer, it is mostly a preventable disease. Simply by modification of diet, maintenance of optimum body weight, and regular physical activity, 30% to 40% of all instances of cancer could be prevented. Modification of diet alone by increasing vegetable and fruit intake could prevent 20% or more of all cases of cancer and may potentially prevent approximately 200,000 cancer-related deaths annually. Because of their safety, low toxicity, antioxidant properties, and general acceptance as dietary supplements, fruits, vegetables, and other dietary elements (phytochemicals and minerals) are being investigated for the prevention of cancer. Extensive research over the past several decades has identified numerous dietary and botanical natural compounds that have chemopreventive potential. In this review, we discuss promising natural chemopreventive compounds, their molecular targets, and their mechanisms, which may help the further design and conduct of preclinical and clinical trials
Conclusion Chemoprevention research has gained momentum through the US Food and Drug Administration approval of tamoxifen and raloxifene for breast cancer risk reduction. Various epidemiological and preclinical findings and the results of several early clinical studies convincingly argue for a definitive role of selected dietary products in the prevention and treatment of cancers. Many of these agents target multiple signal transduction pathways, which vary widely depending on cancer origin. The key challenge to researchers is how best to use this information for effective cancer prevention in populations with different cancer risks. Moreover, low potency and poor bioavailability of dietary agents pose further challenges to scientists. The introduction of synthetic analogs of natural compounds may be a solution for these potency and bioavailability limitations. For example, the synthetic curcumin analog EF24 exhibited approximately 10-fold greater potency than natural curcumin.154 Some natural compounds have exhibited synergism with established chemopreventive agents or with other natural compounds. Since drug-associated toxicity remains a significant barrier for currently available chemotherapeutic and chemopreventive drugs, using natural compounds (which have better safety profiles) as adjuvant therapy with current chemotherapeutic agents may help to mitigate drug-associated toxicities. For example, genistein was found to sensitize prostate cancer to radiation in animal studies122 and a recent clinical trial suggested that soy isoflavones could prevent radiation-induced bladder and bowel adverse effects and erectile dysfunction.188Because of the advances in our understanding of multistep and field carcinogenesis, the introduction of new technologies for screening and early detection, and the emergence of promising molecularly targeted agents, prevention and therapy are beginning to converge at the level of early-phase clinical trials.189 The future full convergence of prevention-therapy drug development will open new avenues for natural compounds in reducing the public health impact of major cancers. However, more preclinical studies and clinical trials are certainly needed to validate the usefulness of these agents either alone or in combination with existing therapies.
Nrf2 as a Master Redox Switch in Turning on the Cellular Signaling Involved in the Induction of Cytoprotective Genes by Some ChemopreventivePhytochemicals Young-Joon Surh, Joydeb Kumar Kundu, Hye-Kyung Na
Affiliation National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, Seoul, South Korea
Abstract A wide array of dietary phytochemicals have been reported to induce the expression of enzymes involved in both cellular antioxidant defenses and elimination/inactivation of electrophilic carcinogens. Induction of such cytoprotective enzymes by edible phytochemicals largely accounts for their cancer chemopreventive and chemoprotective activities. Nuclear factor-erythroid-2-related factor 2 (Nrf2) plays a crucial role in the coordinated induction of those genes encoding many stress-responsive and cytoptotective enzymes and related proteins. These include NAD(P)H:quinone oxidoreductase-1, heme oxygenase-1, glutamate cysteine ligase, glutathione S-transferase, glutathione peroxidase, thioredoxin, etc. In resting cells, Nrf2 is sequestered in the cytoplasm as an inactive complex with the repressor Kelch-like ECH-associated protein 1 (Keap1). The release of Nrf2 from its repressor is most likely to be achieved by alterations in the structure of Keap1. Keap1 contains several reactive cysteine residues that function as sensors of cellular redox changes. Oxidation or covalent modification of some of these critical cysteine thiols would stabilize Nrf2, thereby facilitating nuclear accumulation of Nrf2. After translocation into nucleus, Nrf2 forms a heterodimer with other transcription factors, such as small Maf, which in turn binds to the 5′-upstream cis-acting regulatory sequence, termed antioxidant response elements (ARE) or electrophile response elements (EpRE), located in the promoter region of genes encoding various antioxidant and phase 2 detoxifying enzymes. Certain dietary chemopreventive agents target Keap1 by oxidizing or chemically modifying one or more of its specific cysteine thiols, thereby stabilizing Nrf2. In addition, phosphorylation of specific serine or threonine residues present in Nrf2 by upstream kinases may also facilitate the nuclear localization of Nrf2. Multiple mechanisms of Nrf2 activation by signals mediated by one or more of the upstream kinases, such as mitogen-activated protein kinases, phosphatidylionositol-3-kinase/Akt, protein kinase C, and casein kinase-2 have recently been proposed. This review highlights the cytoprotective gene expression induced by some representative dietary chemopreventive phytochemicals with the Nrf2-Keap1 system as a prime molecular target.
Dietary Cancer Chemopreventive Agents – Targeting Inflammation and Nrf2 Signaling Pathway Tin Oo Khor, Siwang Yu, Ah-Ng Kong
Affiliation Center for Cancer Prevention Research and Department of Pharmaceutics, Ernest-Mario School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, NJ, USA
Abstract Accumulating epidemiological and clinical evidence shows that chronic inflammation plays a critical role in neoplastic transformation and progression. Long-term users of selective cycloxygenase-2 (Cox-2) inhibitors (coxibs) and non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to have a reduced risk of developing colorectal cancer. However, the adverse gastrointestinal and cardiovascular side effects associated with these drugs have limited their routine use for cancer chemoprevention. Basic leucine zipper (bZIP) protein Nrf2, a key transcription factor mediating the antioxidant response is an important modulator of tumor susceptibility in mouse models. Mice lacking Nrf2 are more susceptible to carcinogenesis induced by carcinogens. Moreover, induction of the Nrf2 signaling pathway is essential for many food phytochemicals to exert their cancer chemopreventive activity as demonstrated in many preclinical studies. It has been recently shown that the combination of coxibs or NSAIDs and natural phytochemicals can synergistically inhibit carcinogenesis in rodent models. This review will focus on the role of chronic inflammation and the Nrf2 signaling pathway in carcinogenesis and the feasibility of targeting these signaling pathways with dietary cancer chemopreventive agents and for cancer chemoprevention.