Main Article Content
Cervical cancer is most familiar neoplasm among women worldwide. Surgery, radiotherapy, and chemotherapy are common treatments, however high stage tumors have frequently poor prognosis. HPV 16 and 18 are major etiological factors for cervical cancer. Likewise, epigenetics is the study of inherited changes and modulated gene expression without alteration in DNA sequences. In mammals epigenetic modifications include DNA methylation, histone modifications and miRNA.
Phytochemicals are mainly contained in fruits, seeds, and vegetables as well as in foods supplements. Numerous dietary compounds exhibit potent anti-tumor activities through the reversion of epigenetic alterations associated to oncogenes activation and inactivation of tumor suppressor genes in cervical cancer cell lines SiHa and HeLa, demethylation of the tumour suppressor genes such as RARβ2, MGMT, RASSF1A, DAPK etc. Reversal of hypermethylated genes as a tumor-suppressor gene, is related to inhibition of cell proliferation, development and differentiation. The impact of phytochemicals lead to the reversal of hypermethylation which may help to cure cervical cancer. This study concludes the effect of phytochemicals on genetic and epigenetic modifications and reveals how these modifications help to prevent various types of cancers and improve health outcomes.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J Clin. 2018;68:394-422.
Yeole BB, Kumar AV, Kurkureet A, Sunny L. Population-based survival from cancers of breast, cervix and ovary in women in Mumbai. Asian Pac J Cancer Prev. 2004;5:308–315.
Siegel RL, Miller KD. Jemal Acer statistics. CA Cancer J Clin. 2016;66(1):7-30.
Zur H, Hausen W, Meinhof W, Scheiber G.W. Bornkamm. Attempts to detectvirus-specific DNA in human tumors. I. Nucleic acid hybridizations with complementary RNA of human wart virus. Int. J. Cancer. 1987;13:650–656.
Alshatwi AA, Ramesh E, Periasamy VS, Subash-Babu P. The apoptotic effect of hesperetin on human cervical cancer cells is mediated through cell cycle arrest, death receptor, and mitochondrial pathways. Fundam Clin Pharmacol. 2013;27:581-92.
Sowjanya AP, Jain M, Poli UR, et al. Prevalence and distribution of high-risk human papilloma virus (HPV) types in invasive squamous cell carcinoma of the cervix and in normal women in Andhra Pradesh, India. BMC Infect Dis. 2005;5:116.
Hanahan D, Weinberg R. Hallmarks of cancer: The next generation. Cell. 2011;144:646–676.
Waddington CH. The epigenotype. Endeavour .1942;1:18–20.
Illingworth R, Kerr A, Desousa D, Jorgensen H, Ellis P, Stalker J, et al. A novel CpG island set identifies tissue-specific methylation at developmental gene loci. PLoS Biol. 2008;6:e22.
[PMC free article] [PubMed]
Suter MA, Aagaard-Tillery KM. Environmental influences on epigenetic profiles. Semin Reprod Med. 2009;27:380–390.
Lim U, Song MA. Dietary and lifestyle factors of DNA methylation. Methods Mol Biol. 2012;863:359–376.
Hotchkiss RD. The quantitative separation of purines, pyrimidines, andnucleosides by paper chromatography. J Biol Chem.1948;175:315–332.
Gruenbaum Y, Naveh-Many T, Cedar H, Razin A. Sequence specificity of methylation in higher plant DNA. Nature. 1981;292:860–862.
Yoo CB, Jones PA. Epigenetic therapy of cancer: Past, present and future. Nat Rev Drug Discov. 2006;5(1):37–50.
Ehrlich M, Gama-Sosa MA, Huang LH, Midgett RM, Kuo KC, McCune RA, Gehrke C. Amount and distribution of 5-methylcytosine in humans DNA from different types of tissues of cells. Nucleic Acids Res. 1982;10:2709-2721.
Goll MG, Kirpekar F, Maggert KA, Yoder JA, Hsieh CL, Zhang X, Golic KG, Jacobsen SE, Bestor TH. Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2. Science. 2006;311:395–398.
Jurkowska RZ, Jurkowski TP, Jeltsch A. Structure and function of mammalian DNA methyltransferases. Chem Biochem. 2010;12:206–222.
Diaz LA Jr, Bardelli A. Liquid biopsies: Genotyping circulating tumor DNA. J Clin Oncol. 2014;32(6):579–86.
Kouzarides T. Regulation of chromatin by histone modifications. Cell Res. 2011;21:381–395.
Cedar H, Bergman Y. Linking DNA methylation and histone modification: Patterns and paradigms. Nat Rev Genet. 2009;10:295–304.
Fullgrabe J, Kavanagh E, Joseph B. Histone onco-modifications. Oncogene. 2011;30:3391–3403.
Doi A, Park I-H, Wen B, et al. Differential methylation of tissue- and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts. Nat Genet. 2009;41(12):1350–1353.
Croce CM. Causes and consequences of microRNA dysregulationin cancer. Nat Rev Genet. 2009;10:704–714.
Negrini M, Ferracin M, Sabbioni S, Croce CM. MicroRNAs in human cancer: From research to therapy. J Cell Sci. 2007;120:1833–1840.
Mager DL, Humphries RK, Kuchenbauer F. MiRNAs, epigenetics, and cancer. Mamm Genome. 2008;19(7–8):517–525.
Suzuki T, Miyata N. Epigenetic control using natural products and synthetic molecules. Curr Med Chem. 2006;13:935–958.
Palakurthy RK, Wajapeyee N, Santra MK, Gazin C, Lin L, Gobeil S, Green MR. Epigenetic silencing of the RASSF1A tumor suppressor gene through HOXB3-mediated induction of DNMT3B expression. Mol Cell. 2009;36:219-230.
Bhattacharya SK, Ramchandani S, Cervoni N, Szyf M. A mammalian protein with specific demethylase activity for mCpG DNA. Nature. 1999;397(6720):579–83.
Mani S, Herceg Z. DNA demethylating agents and epigenetic therapy of cancer. Adv Genet. 2010;70:327-40.
Donninger H, Clark J, Rinaldo F, Nelson N, Barnoud T, Schmidt ML, et al. The RASSF1A tumor suppressor regulates XPA-mediated DNA repair.Mol Cell Biol. 2015;35(1):277-87.
Garzon R, Calin GA, et al. MicroRNAs in Cancer. Annu Rev Med. 2009;60:167–179.
Burdge GC, Lillycrop KA. Nutrition, epigenetics, and developmental plasticity: implications for understanding human disease. Annu Rev Nutr. 2010;30:315–339.
Duthie SJ. Epigenetic modifications and human pathologies: Cancer and CVD. Proc Nutr Soc. 2011;70(1):47–56.
Hayashi K, Yokozaki H, Naka K, Yasui W, Lotan R, Tahara E. Overexpression of retinoic acid receptor beta induces growth arrest and apoptosis in oral cancer cell lines. Jpn J Cancer Res. 2001;92:42–50.
Yang Q, Sakurai T, Kakudo K. Retinoid, retinoic acid receptor beta and breast cancer. Breast Cancer Res Treat. 2002;76:167-173.
Jeong JH, An JY, Kwon YT, Rhee JG, Lee YJ. Cancer cell-specific inhibition of cell cycle progression. J. Cell. Biochem. 2009;106:73–82.
Jha AK, Nikbakht M, Parashar G, et al. Reversal of hypermethylation and reactivation of the RARbeta2 gene by natural compounds in cervical cancer cell lines. Folia Bio (Praha). 2010;56:195-200.
Mittag F, Kuester D, Vieth M, Peters B, Stolte B, Roessner A. Schneider-Stock R. DAPK promotor methylation is an early event in colorectal carcinogenesis. Cancer Lett. 2006;240:69–75.
Yamanaka M, Watanabe M, Yamada Y, Takagi A, Murata T, Takahashi H, Suzuki H, Ito H, Tsukino H, Katoh T, Sugimura Y, Shiraishi T. Altered methylation of multiple genes in carcinogenesis of the prostate. Int J Cancer. 2003;106:382–387.
Deiss LP, Feinstein E, Berissi H, Cohen O, Kimchi A. Identification of a novel serine/ threonine kinase and a novel 15-kD protein as potential mediators of the gamma interferon-induced cell death. Genes Dev. 1995;9:15-30.
Shohat G, Shani G, Eisenstein M, Kimchi A. The DAP-kinase familyof proteins: Study of a novel group of calcium-regulated death-promoting kinases. Biochem Biophys Acta. 2002;1600:45-50.
Inbal B, Cohen O, Polak-Charcon S, Kopolovic J, Vadai E, Eisenbach L, Kimchi A. DAP kinase links the control of apoptosis to metastasis. Nature. 1997;390:180-184.
Dong SM, Kim HS, Rha SH, Sidransky D. Promoter hyper methylation of multiple genes in carcinoma of the uterine cervix. Clin Cancer Res. 2001;7:1982-1986.
Jacobsen AV, Murphy JM. The secret life of kinases: Insights into non-catalytic signalling functions from pseudo kinases. Biochem Soc Trans. 2017;45:665–681.
Yokoyama T, Kosaka Y, Mizuguchi M. Structural insight into the interactions between death-associated protein kinase 1and natural flavonoids. J Med Chem. 2015;58:7400–7408.
Kuramochi M, Fukuhara H, Nobukuni T, Kanbe T, Maruyama T, Ghosh HP, Pletcher M, Isomura M, Onizuka M, Kitamura T, et al. TSLC1 is a tumor-suppressor gene in human non-small-cell lung cancer. Nat Genet. 2001;27:427-430.
Steenbergen RD, Kramer D, Braakhuis BJ, Stern PL, Verheijen RH, Meijer CJ, Snijders PJ. TSLC1 gene silencing in cervical cancer cell lines and cervical neoplasia. J Natl Cancer Inst. 2004;96:294-305.
Fukuhara H, Kuramochi M, Fukami T, Kasahara K, Furuhata M, Nobukuni T, Maruyama T, Isogai K, Sekiya T, Shuin T, et al. Promoter methylation of TSLC1 and tumor suppression by itsgene product in human prostate cancer. Jpn J Cancer Res. 2002;93:605-609.
Lung HL, Cheung AK, Xie D, Cheng Y, Kwong FM, Murakami Y, Guan XY, Sham JS, Chua D, Protopopov AI, et al. TSLC1 is a tumor suppressor gene associated with metastasis in nasopharyngeal carcinoma. Cancer Res. 2006;66:9385-9392.
Roy SK, Chen Q, Fu J, Shankar S, Srivastava RK. Resveratrol inhibits growth of orthotopic pancreatic tumors through activation of FOXO transcription factors. PLoS One. 2011;6(9):e25166
Fang M, Chen D, Yang CS. Dietary polyphenols may affect DNA methylation. J Nutr. 2007;137(Suppl1):223S–228S.
Fang MZ, Wang Y, Ai N, Hou Z, Sun Y, Lu H, Welsh W, Yang CS. Tea polyphenol(_)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation silenced genes in cancer cell lines. Cancer Res. 2003;63(22):7563–7570.
Fang MZ, Chen D, Sun Y, Jin Z, Christman JK, et al. Reversal of hypermethylation and reactivation of p16INK4a, RARbeta, and MGMT genes by genistein and other isoflavones from soy. Clin Cancer Res. 2005;11(19 Pt 1):7033–7041.
Doughari JH, Human IS, Benadé AJ, Ndakidemi PA. Phytochemicals as chemotherapeutic agents and antioxidants: Possible solution to the control of antibiotic resistant vero cytotoxin producing bacteria. Plantamedica. 2009;3(11):839–48.
Liu RH. Potential synergy of phytochemicals in cancer prevention: Mechanism of action. J Nutr. 2004;134(Suppl12):3479S–85.
Uramova S, Kubatka P, Dankova Z, Kapinova A, Zolakova B, Samec M, Zubor P, Zulli A, Valentova V, Kwon TK, Solar P, Kello M, Kajo K, Busselberg D, Pec M, Danko J. Plant natural modulators in breast cancer prevention: status quo and future perspectives reinforced by predictive, preventive, and personalized medical approach. 2018;9(4):403–419.
Levin DA. Plant phenolics: An ecological perspective. Am Nat. 1971;105(942):157–81.
Watson WG, Beaver ML, Williams ED, Dashwood HR, Ho E. Phytochemicals from cruciferous vegetables, epigenetics, and prostate cancer prevention. AAPSJ. 2013;15(4):951–61.
Acharya A, Das I, Chandhok D, Saha T. Redox regulation in cancer: A double-edgeds word with the rapeutic potential. Oxid Med Cell Longev. 2010;3(1):23–34.
Islam MB, Sarkar MMH, Shaﬁque MZ, Jalil MA, Haque MZ, Amin R. Phytochemical screening and anti-microbial activity studies on leeamacrophylla seed extracts. J Sci Res. 2013;5(2).
Mateos R, Goya L, Bravo L. Uptake and metabolism of hydroxyl cinnamic acids (chlorogenic, caffeic, and ferulic acids) by HepG2cellsas a model of the human liver. J Agric Food Chem. 2006;54(23):8724–32.
Forster GM, Raina K, Kumar A, Kumar S, Agarwal R, Chen MH, et al. Rice varietal differences in bioactive bran components for inhibition of colorectal cancer cell growth. Food Chem. 2013;141(2):1545–52.
Stahl W, Sies H. Bioactivity and protective effects of natural carotenoids. Biochim Biophys Acta. 2004;1740(2):101–7.
Russo GL. Ins and outs of dietary phytochemicals in cancer chemoprevention. Biochem Pha rmacol. 2007;74(4):533–44.
Ambrósio CLB, de Arruda Camara e Siqueira Campos F, de Faro ZP. Carotenóides como alternativa contra a hipovitaminose A. Revista de Nutrição. 2006;19(2):233–243.
Manetta A, Schubbert T, Chapman J, Schell MJ, Peng YM, Liao SY, Meyskens FJ. b-Carotene treatment of cervical intraepithelial neoplasia: A Phase II study. Cancer Epidemiol. Biomark. Prev. 1996;5:929–932.
Deiters A, Martin SF. Synthesis of oxygen- and nitrogen-containing heterocycles by ring-closing meta thesis. Chem Rev. 2004;104(5):2199238.
Su C, Zhang P, Song X, Shi Q, Fu J, Xia X, et al. Tetrachloro benzoquinone activates Nrf 2 signaling by Keap 1 cross-linking and ubiquitin translocation but not Keap1-Cullin3 complex dissociation. Chem Res Toxicol. 2015;28(4):765–74.
Giardi MT, Touloupakis E, Bertolotto D, Mascetti G. Preventive or potential therapeutic value of nutraceuticals against ionizing radiation-induced oxidative stress in exposed subjects and frequent fliers. Int J Mol Sci. 2013;14(8):17168–92.
Iciek M, Kwiecien I, Wlodek L. Biological properties of garlic and garlic-derived organosulfur compounds. Environ Mol Mutagen. 2009;50:247–265.
Druesne N, Pagniez A, Mayeur C, Thomas M, Cherbuy C, Duée PH, et al. Diallyl disulfide (DADS) increases histone acetylation and p21(waf1/cip1) expression in human colon tumor cell lines. Carcinogenesis. 2004;25:1227–1236.
Chirumbolo S. Quercetin in cancer prevention and therapy. Integr. Cancer Ther. 2013;12:97–102.
Graefe EU, Wittig J, Mueller S, Riethling AK, Uehleke B, Drewelow B, Pforte H, Jacobasch G, Derendorf H, Veit M. Pharmacokinetics and bioavailability of quercitol glycosides in humans. J. Clin. Pharmacol. 2001;41:492–499.
D'Avila Farias M, Oliveira PS, Dutra FS, Fernandes TJ, de Pereira CM, de Oliveira SQ, et al. Eugenol derivatives as potential anti-oxidants: Is phenolic hydroxyl necessary to obtain an effect? J Pharm Pharmacol. 2014;66:733-46.
Miyazawa M, Hisama M. Antimutagenic activity of Phenyl propanoids from clove (Syzygium aromaticum). J Agric Food Chem. 2003;51:6413-22.