REVIEW STUDY ON ROLE OF NATURAL COMPOUNDS IN CANCER TREATMENTHTML Full Text
REVIEW STUDY ON ROLE OF NATURAL COMPOUNDS IN CANCER TREATMENT
Seyed Hossein Hassanpour * 1 and Azade Roohipoor 2
Department of Pharmacology 1, Faculty of Pharmacy, Jundishapour University of Medical Sciences, Ahvaz, Iran.
Department of Biochemistry 2, Taft University of Payame - Noor, Yazd, Iran.
ABSTRACT: Today, cancer can be considered as a serious threat to human health because its treatment is difficult and expensive. Also, genetic modifications are considered as risk factors for many diseases including cancer. To discover a benefit and promising therapeutic is one of the main goals research on cancer. Environmental and nutritional factors can affect the organism through genetic and epigenetic changes. Natural compounds found in plants and can be a potential source for cancer treatment. It has recently been considered the role of some of these compounds in genetic and epigenetic changes. In this study, we mentioned some of these cases. This study is a beneficial review of the relationship between nutrition and cancer by searching for the related article.
Cancer, Natural compounds, Genetic, Epigenetic changes
INTRODUCTION: Nutrition is one of the most important factors affecting genetic and epigenetic. Many foods have properties of therapeutic and preventive against many diseases by interference in genetic and epigenetic processes. Cancer is one of the diseases that it has frequently been studied in this field. Many studies have been showed that nutritional factors found in fruits and vegetables lead to activation of tumor suppressor genes, apoptosis, and suppression of cancer genes through genetic and epigenetic processes 1, 2. It has well been shown that food phytochemicals such as polyphenols, genistein, resveratrol, and curcumin could have had anti-cancer activity by effects of genetic and epigenetic 3, 4.
Dietary polyphenols found in fruits and vegetables are an essential part of the human diet 5. Common polyphenols such as epigallocatechin gallate (EGCG), curcumin and resveratrol in green tea, turmeric and grape, respectively have a pivotal role in reducing and preventing cancer so that they inhibit DNA methyltransferase (DNMT) and lead to changes in the histones 6, 7. The study aimed to review the effect of natural compounds on cancer by focusing on epigenetic processes.
Review Method: In this review study, we searched paper related to the role of natural compounds in the treatment of cancer with keywords such as natural compounds and cancer, natural compounds and epigenetic change during cancer in databases include the web of science, PubMed and Scopus. Then, the papers were fully read and summarized here.
The Effects of Natural Compounds in Cancer Treatment: There is resveratrol in food and normally in several plants, including peanut, strawberry, blueberry, however it has majority been seen in grape peel 8. The properties such as antioxidant, anti-inflammation and anti-cancer related to resveratrol occur through different biochemical and molecular pathways 9. Also, the anti-proliferative property of resveratrol against cancers of breast, prostate, lung, and colon has been reported 10, 11.
Studies have been showed inhibitory effects of resveratrol on DNMT is lower than EGCG. However, resveratrol inhibits inactivation of BRCA1 as tumor suppressor genes 12. Resveratrol activates the SIRT1 and P300 that known as a histone deacetylase inhibitor 13. Histone deacetylases are responsible for removing acetyl groups from lysine in histone structure. To date, it has been identified at least 18 isozymes of histone deacetylase, which categorize in several class. In several studies, it has been reported the association between its class I with progressing of malignant tumors, but this association has been less in its class II 14. Many studies have been examined the effects of resveratrol against aging. Based on study performed by Baur et al., 2006 resveratrol could increase longevity and health in mice with a high-calorie diet 15. Today than in the past, it has been confirmed the antioxidant activity of resveratrol. It inhibits oxidative damage against DNA in the presence of iron and copper 16.
The Brassicaceae family is rich in glucosinolate. Hydrolysis glucosinolate by myrosinase leads to the production of indole and isothiocyanate 17. According to studies, isothiocyanate has pre-apoptotic and anti-proliferative properties and anti-carcinogenic effects 18. Treatment with isothiocyanate leads to improvement of tumorigenesis in esophageal 19. Allyl isothiocyanate found in broccoli can increase histone acetylation in mice’s erythroleukemia cells. Phenylhexyl isothiocyanate as a synthetic isothiocyanate inhibits histone deacetylase, hypomethylation P16 and hyper-methylation histone H3 20. Also, phenylhexyl Isothiocyanate is affected in p21 activation, cell cycle arrest in prostate cancer and leukemia cells by inhibition of histone deacetylase activity required for chromatin remodeling 21. Sulforaphane is another isothiocyanates, which is found in the Brassicaceae family such as broccoli. The studies have been showed that it has anticancer activity 22, 23. Sulforaphane can induce apoptosis and influence cell cycle through inhibition of histone deacetylase; thus; it is involved in the regulation of cancer-related genes 24, 25. Based on previous studies, treatment with sulforaphane inhibits histone deacetylase activity in prostate cancer. It also leads to inhibition of DNA methyltransferase in breast cancer and expression of the human telomerase gene in (Htert) in more than 90% of cancer 26, 27.
Isoflavones (genistein) are a group of flavonoids; in fact, they are the largest class of polyphenols. Polyphenols found in some plants such as soybean. Study on isoflavones has been showed that they have anti-cancer property. Among the isoflavones, most studies have been conducted on genistein, and it has been found that genistein as a phytoestrogen can be a promising compound to prevent cancer 28. Several mechanisms have been attributed to the anti-cancer effects of genistein, including the ability to regulate genes transcription, DNA methylation and histone acetylation 29. The studies on prostate cancer cells have been demonstrated that genistein results in the expression of tumor suppressor genes (p21 and p16) by changes in histone methylation 30. Genistein inhibits DNA methyltransferase (DNMT1 3a, 3b) and increases the acetylation through an increment of histone acetyltransferase activity. Also, genistein and other isoflavones lead to regulation of miRNA expression in cancer cells 31, 32.
Curcumin is a polyphenol that turmeric is its source so that curcumin is responsible for the yellow color of turmeric. Curcumin has anti-inflammatory, antioxidant and anti-cancer properties and it is used as a therapeutic agent in Indian and Chinese medicine 33, 34. Evidence suggests that curcumin as an affecting factor on DNA hypomethylation lead to facilitation of proto-oncogene expression 35, 36. Curcumin has epigenomic effects in cancer cells because overall epigenetic methylation has been seen after treatment curcumin 37. Also, it leads to the expression of GADD 153 and induction of apoptosis in lung cancer cells 38. Curcumin inhibits histone acetyltransferase and histone deacetylase so that these events lead to changes in the histones.
According to performed studies, treatment with curcumin results in inhibition of histone acetyltransferase activity and ultimately the reduction of acetylation in histones H3 and H4 in brain cells. Also, curcumin is main factor histone methylation in several promoters and inactivation of several genes. Recent studies have been demonstrated that inhibition of histone acetyltransferase has a possible role in cancer treatment. This view is a strong strategy for the treatment of cancer through cell cycle arresting and apoptosis induction 39, 40. Several studies have been indicated that curcumin can inhibit the activity of p300/CBP in leukemia and uterus cancer 41. There is also evidence that curcumin inhibits histone hypermethylation by histone deacetylase inhibitor in peripheral blood lymphocytes and cancer cells 42.
In previous studies, it has been reported that compounds in tea can prevent many diseases such as cancer. Indeed, tea contains polyphenolic compounds that have a protective effect against reactive oxygen species 3. Epigallocatechin gallate (EGCG) comprises over 50% active ingredients of tea, and its anti-cancer activity has been widely studied 43, and its preventive effect against cancer has been proven 44, 45. Epigallocatechin gallate (EGCG) acts as anti-cancer compounds through several different mechanisms such as apoptosis induction, cell cycle arrest, reduction of oxidative stress, inhibition of proliferation and angiogenesis of cancer cells 46 - 49.
Based on previous studies that Epigallocatechin gallate (EGCG) reduces DNMT activity in esophageal cancer cells that leads to hyper-methylation of tumor suppressor genes and subsequently increase their activity 50. EGCG results in a reduction of acetylation in p65 as a transcription factor by inhibition of histone acetyltransferase that this event leads to inhibition of inflammation due to reduction of NF-Ҡb and IL-6 levels 49. Also, it increases the expression of tumor suppressor genes through the promotion of hypermethylation status in oral squamous cell carcinoma cells 51. Moreover, Studies have been revealed that EGCG makes moderation of miRNA expression in liver cancer 52.
CONCLUSION: In this study, we reviewed the anticancer effects of natural compounds in the diet, which can be effective on important processes involved in the initiation and progression of cancer. Numerous studies have been showed that cancer alike other chronic diseases such as diabetes, cardiovascular disease are associated with metabolic stress and chronic inflammation. Also, the expression of genes involved in inflammation is controlled by epigenetic mechanisms. Natural compounds in the diet moderate inflammatory genes expression by an effect on epigenetic processes.
Based on empirical and laboratory evidence mentioned in this review, epigenetic changes are one of the main mechanisms related to natural compounds to control growth tumor and metastasis. Epigenetic changes lead to a lack of normal regulation of genes expression, oncogenes activation, and inhibition of tumor suppressor genes in early and advanced stages of carcinogenesis. Therefore, natural compounds are useful in order to prevention and treatment of cancer and can be effective in the development of new drugs against cancer. Results of performed studies in this field manifest a dire need to consume natural products to health promotion.
CONFLICT OF INTEREST: The authors declare that there is no conflict of interest regarding this paper.
- Li Y and Tollefsbol TO: p16 INK 4a suppression by glucose restriction contributes to human cellular lifespan extension through SIRT1-mediated epigenetic and genetic mechanisms. PLoS One 2011; 6(2): e17421.
- Paluszczak J, Krajka-Kuźniak V and Baer-Dubowska W: The effect of dietary polyphenols on the epigenetic regulation of gene expression in MCF7 breast cancer cells. Toxicology Letters 2010; 192(2): 119-25.
- Link A, Balaguer F and Goel A: Cancer chemoprevention by dietary polyphenols: promising role for epigenetics. Biochemical Pharmacology 2010; 80(12): 1771-92.
- Lee KW, Lee HJ and Lee CY: Vitamins, phytochemicals, diets, and their implementation in cancer chemo-prevention. Critical Reviews in Food Science and Nutrition 2004; 44(6): 437-52.
- Bravo L: Polyphenols: chemistry, dietary sources, metabolism, and nutritional significance. Nutrition reviews 1998; 56(11): 317-33.
- Shukla Y and Singh R: Resveratrol and cellular mechanisms of cancer prevention. Annals of the New York Academy of Sciences 2011; 1215(1): 1-8.
- Cui X, Jin Y, Hofseth AB, Pena E, Habiger J and Chumanevich A: Resveratrol suppresses colitis and colon cancer associated with colitis. Cancer Prevention Research 2010; 3(4): 549-59.
- Das DK, Mukherjee S and Ray D: Resveratrol and red wine, healthy heart and longevity. Heart failure reviews 2010; 15(5): 467-77.
- Athar M, Back JH, Kopelovich L, Bickers DR and Kim AL: Multiple molecular targets of resveratrol: Anti-carcinogenic mechanisms. Archives of Biochemistry and Biophysics 2009; 486(2): 95-102.
- Mao QQ, Bai Y, Lin YW, Zheng XY, Qin J and Yang K: Resveratrol confers resistance against taxol via induction of cell cycle arrest in human cancer cell lines. Molecular Nutrition and Food Research 2010; 54(11): 1574-84.
- Vanamala J, Reddivari L, Radhakrishnan S and Tarver C: Resveratrol suppresses IGF-1 induced human colon cancer cell proliferation and elevates apoptosis via suppression of IGF-1R/Wnt and activation of p53 signaling pathways. BMC Cancer 2010; 10(1): 238.
- Papoutsis AJ, Lamore SD, Wondrak GT, Selmin OI and Romagnolo DF: Resveratrol prevents epigenetic silencing of BRCA-1 by the aromatic hydrocarbon receptor in human breast cancer cells. The Journal of Nutrition 2010; 140(9): 1607-14.
- Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S and Wood JG: Small molecule activators of sirtuins extend Saccharomyces cerevisiae Nature 2003; 425(6954): 191-6.
- Hoshino I and Matsubara H: Recent advances in histone deacetylase targeted cancer therapy. Surgery Today 2010; 40(9): 809-15.
- Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C and Kalra A: Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006; 444(7117): 337-42.
- Azmi AS, Bhat SH and Hadi S: Resveratrol–Cu (II) induced DNA breakage in human peripheral lymphocytes: implications for anticancer properties. FEBS Letters 2005; 579(14): 3131-5.
- Hayes JD, Kelleher MO and Eggleston IM: The cancer chemopreventive actions of phytochemicals derived from glucosinolates. European J of Nutrit 2008; 47(2): 73-88.
- Fimognari C, Lenzi M and Hrelia P: Chemoprevention of cancer by isothiocyanates and anthocyanins: mechanisms of action and structure-activity relationship. Current Medicinal Chemistry 2008; 15(5): 440-7.
- Wilkinson JT, Morse MA, Kresty LA and Stoner GD: Effect of alkyl chain length on inhibition of N-nitrosomethyl benzylamine - induced esophageal tumorigenesis and DNA methylation by isothiocyanates. Carcinogenesis 1995; 16(5): 1011-5.
- Lu Q, Lin X, Feng J, Zhao X, Gallagher R and Lee MY: Phenylhexyl isothiocyanate has a dual function as histone deacetylase inhibitor and hypomethylating agent and can inhibit myeloma cell growth by targeting critical pathways. Journal of Hematology and Oncology 2008; 1(1): 6.
- Beklemisheva AA, Fang Y, Feng J, Ma X, Dai W and Chiao JW: Epigenetic mechanism of growth inhibition induced by phenylhexyl isothiocyanate in prostate cancer cells. Anticancer Research 2006; 26(2A): 1225-30.
- Cheung KL and Kong AN: Molecular targets of dietary phenethyl isothiocyanate and sulforaphane for cancer chemoprevention. The AAPS Journal 2010; 12(1): 87-97.
- Meeran SM, Patel SN and Tollefsbol TO: Sulforaphane causes epigenetic repression of hTERT expression in human breast cancer cell lines. PloS One 2010; 5(7): e11457.
- Pledgie-Tracy A, Sobolewski MD and Davidson NE: Sulforaphane induces cell type-specific apoptosis in human breast cancer cell lines. Molecular Cancer Therapeutics 2007; 6(3): 1013-21.
- Bhamre S, Sahoo D, Tibshirani R, Dill DL and Brooks JD: Temporal changes in gene expression induced by sulforaphane in human prostate cancer cells. The Prostate 2009; 69(2): 181-90.
- Telang U, Brazeau DA and Morris ME: Comparison of the effects of phenethyl isothiocyanate and sulforaphane on gene expression in breast cancer and normal mammary epithelial cells. Experimental Biology and Medicine 2009; 234(3): 287-95.
- Myzak MC, Tong P, Dashwood WM, Dashwood RH and Ho E: Sulforaphane retards the growth of human PC-3 xenografts and inhibits HDAC activity in human subjects. Experimental biology and medicine 2007; 232(2): 227-34.
- Barnes S: Effect of genistein on in-vitro and in-vivo models of cancer. The Journal of Nutrition 1995; 125(3): 777S.
- Li Y, Liu L, Andrews LG and Tollefsbol TO: Genistein depletes telomerase activity through cross‐talk between genetic and epigenetic mechanisms. International journal of Cancer 2009; 125(2): 286-96.
- Majid S, Kikuno N, Nelles J, Noonan E, Tanaka Y and Kawamoto K: Genistein induces the p21WAF1/CIP1 and p16INK4a tumor suppressor genes in prostate cancer cells by epigenetic mechanisms involving active chromatin modification. Cancer Research 2008; 68(8): 2736-44.
- Li Y, Vandenboom TG, Kong D, Wang Z, Ali S and Philip PA: Up-regulation of miR-200 and let-7 by natural agents leads to the reversal of epithelial-to-mesenchymal transition in gemcitabine-resistant pancreatic cancer cells. Cancer Research 2009; 69(16): 6704-12.
- Parker L, Taylor D, Kesterson J, Metzinger D and Gercel-Taylor C: Modulation of microRNA associated with ovarian cancer cells by genistein. European Journal of Gynecological Oncology 2008; 30(6): 616-21.
- Maheshwari RK, Singh AK, Gaddipati J and Srimal RC: Multiple biological activities of curcumin: a short review. Life Sciences 2006; 78(18): 2081-7.
- Goel A and Aggarwal BB: Curcumin, the golden spice from Indian saffron, is a chemosensitizer and radio-sensitizer for tumors and chemoprotector and radio-protector for normal organs. Nutrition and Cancer 2010; 62(7): 919-30.
- Liu Z, Xie Z, Jones W, Pavlovicz RE, Liu S and Yu J: Curcumin is a potent DNA hypomethylation agent. Bioorganic and Medicinal Chemistry Letters 2009; 19(3): 706-9.
- Fu S and Kurzrock R: Development of curcumin as an epigenetic agent. Cancer 2010; 116(20): 4670-6.
- Chen Y: Curcumin, a potent anti‐tumor reagent, is a novel histone deacetylase inhibitor regulating B‐NHL cell line Raji proliferation. Acta Pharmacologica Sinica 2005; 26(5): 603-9.
- Saha A, Kuzuhara T, Echigo N, Fujii A, Suganuma M and Fujiki H: Apoptosis of human lung cancer cells by curcumin-mediated through up-regulation of" growth arrest and DNA damage-inducible genes 45 and 153". Biological and Pharmaceutical Bulletin 2009; 33(8): 1291-9.
- Kang SK, Cha SH and Jeon HG: Curcumin-induced histone hypoacetylation enhances caspase-3-dependent glioma cell death and neurogenesis of neural progenitor cells. Stem cells and development 2006; 15(2): 165-74.
- Lee YH, Hong SW, Jun W, Cho HY, Kim HC and Jung MG: Anti-histone acetyltransferase activity from allspice extracts inhibits androgen receptor-dependent prostate cancer cell growth. Bioscience, Biotechnology, and Biochemistry 2007; 71(11): 2712-9.
- Marcu MG, Jung YJ, Lee S, Chung EJ, Lee MJ and Trepel J: Curcumin is an inhibitor of p300 histone acetyl-transferase. Medicinal Chemistry 2006; 2(2): 169-74.
- Kutluay SB, Doroghazi J, Roemer ME and Triezenberg SJ: Curcumin inhibits herpes simplex virus immediate-early gene expression by a mechanism independent of p300/ CBP histone acetyltransferase activity. Virology 2008; 373(2): 239-47.
- Lin JK, Liang YC and Lin-Shiau SY: Cancer chemoprevention by tea polyphenols through mitotic signal transduction blockade. Biochemical Pharmacology 1999; 58(6): 911-5.
- Chen PN, Chu SC, Kuo WH, Chou MY, Lin JK and Hsieh YS: Epigallocatechin-3 gallate inhibits invasion, epithelial-mesenchymal transition, and tumor growth in oral cancer cells. Journal of Agricultural and Food Chemistry 2011; 59(8): 3836-44.
- Tu SH, Ku CY, Ho CT, Chen CS, Huang CS and Lee CH: Tea polyphenol (−)‐epigallocatechin‐3‐gallate inhibits nicotine‐and estrogen‐induced α9‐nicotinic acetylcholine receptor upregulation in human breast cancer cells. Molecular Nutrition and Food Research 2011; 55(3): 455-66.
- Yang CS, Lambert JD and Sang S: Antioxidative and anti-carcinogenic activities of tea polyphenols. Archives of Toxicology 2009; 83(1): 11-21.
- Li Y and Tollefsbol TO: Impact on DNA methylation in cancer prevention and therapy by bioactive dietary components. Current Medicinal Chemistry 2010; 17(20): 2141-51.
- Farabegoli F, Papi A, Bartolini G, Ostan R and Orlandi M: (-)-Epigallocatechin-3-gallate downregulates Pg-P and BCRP in a tamoxifen resistant MCF-7 cell line. Phytomedicine 2010; 17(5): 356-62.
- Balasubramanian S, Adhikary G and Eckert RL: The Bmi-1 polycomb protein antagonizes the (−)-epigallocatechin-3-gallate-dependent suppression of skin cancer cell survival. Carcinogenesis 2010; 31(3): 496-503.
- Fang MZ, Wang Y, Ai N, Hou Z, Sun Y and Lu H: Tea polyphenol (−)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer Research 2003; 63(22): 7563-70.
- Kato K, Long N, Makita H, Toida M, Yamashita T and Hatakeyama D: Effects of green tea polyphenol on methylation status of RECK gene and cancer cell invasion in oral squamous cell carcinoma cells. British Journal of Cancer 2008; 99(4): 647-54.
- Tsang WP and Kwok TT: Epigallocatechin gallate up-regulation of miR-16 and induction of apoptosis in human cancer cells. The Journal of Nutritional Biochemistry 2010; 21(2): 140-6.
How to cite this article:
Hassanpour SH and Roohipoor A: Review study on role of natural compounds in cancer treatment. Int J Pharmacognosy 2017; 4(8): 257-61. doi link: http://dx.doi.org/10.13040/IJPSR.0975-8232.IJP.4(8).257-61.
This Journal licensed under a Creative Commons Attribution-Non-commercial-Share Alike 3.0 Unported License.
S. H. Hassanpour * and A. Roohipoor
Department of Pharmacology, Faculty of Pharmacy, Jundishapour University of Medical Sciences, Ahvaz, Iran.
17 March 2017
23 May 2017
30 May 2017
01 August 2017