Phytochemicals in cervical cancer: an epigenetic overview

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References

• 1. Sung H, Ferlay J, Siegel RL et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71(3), 209–249 (2021). • This reference address the recent statistics of different cancers in several countries.
  MedlineGoogle Scholar
• 2. Ferlay J, Colombet M, Soerjomataram I et al. Cancer Today. International Agency for Research on Cancer. Global Cancer Observatory, Lyon, France (2021).
  Google Scholar
• 3. American Cancer Society. Cancer Facts & Figures 2023.. American Cancer Society, Atlanta, USA (2023). www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/2023-cancer-facts-figures.html
  Google Scholar
• 4. WHO. Institut Català d'Oncologia (ICO), Information Centre on HPV and Cervical Cancer (2022): human papillomavirus and related cancers in Egypt. Summ. Rep. Updat. 22 (2022).
  Google Scholar
• 5. Chan CK, Aimagambetova G, Ukybassova T, Kongrtay K, Azizan A. Human papillomavirus infection and cervical cancer: epidemiology, screening, and vaccination – review of current perspectives. J. Oncol. 2019, 1–11 (2019).
  Google Scholar
• 6. Lin M, Ye M, Zhou J, Wang ZP, Zhu X. Recent advances on the molecular mechanism of cervical carcinogenesis based on systems biology technologies. Comput. Struct. Biotechnol. J. 17, 241–250 (2019).
  Medline CASGoogle Scholar
• 7. Wassie M, Argaw Z, Tsige Y, Abebe M, Kisa S. Survival status and associated factors of death among cervical cancer patients attending at Tikur Anbesa Specialized Hospital, Addis Ababa, Ethiopia: a retrospective cohort study. BMC Cancer 19, 1 (2019).
  MedlineGoogle Scholar
• 8. Johnson CA, James D, Marzan A, Cancer AMC. An overview of pathophysiology and management. Semin. Oncol. Nursing Apr. 35(2), 166–174 (2019).
  MedlineGoogle Scholar
• 9. Castellsagué X. Natural history and epidemiology of HPV infection and cervical cancer. Gynecol. Oncol. 1(110), 3 (2008).
  Google Scholar
• 10. García-Closas R, Castellsagué X, Bosch X, González CA. The role of diet and nutrition in cervical carcinogenesis: a review of recent evidence. Int. J. Cancer 117(4), 629–637 (2005).
  Medline CASGoogle Scholar
• 11. Campos NG, Sharma M, Clark A et al. The health and economic impact of scaling cervical cancer prevention in 50 low- and lower-middle-income countries. Int. J. Gynecol. Obstet. 138, 47–56 (2017).
  MedlineGoogle Scholar
• 12. Manaf R, Ismail S, Cecilia N. Global burden of cervical cancer: a literature review. Int. J. Public Heal. Clin. Sci. 4(2), (2017).
  Google Scholar
• 13. LaVigne AW, Triedman SA, Randall TC, Trimble EL, Viswanathan AN. Cervical cancer in low- and middle-income countries: addressing barriers to radiotherapy delivery. Gynecol. Oncol. Rep. 22, 16–20 (2017).
  MedlineGoogle Scholar
• 14. Lelchuk A, Morin N, Bain K. Squamous cell carcinoma of cervix origin with rare metastasis to the colon. AME Case Rep. 2, 23 (2018).
  MedlineGoogle Scholar
• 15. Bhat S, Kabekkodu SP, Noronha A, Satyamoorthy K. Biological implications and therapeutic significance of DNA methylation regulated genes in cervical cancer. Biochimie 121, 298–311 (2016).
  Medline CASGoogle Scholar
• 16. Sharma A, Kulkarni V, Bhaskaran U et al. Profile of cervical cancer patients attending tertiary care hospitals of Mangalore, Karnataka: a 4 year retrospective study. J. Nat. Sci. Biol. Med. 8(1), 125–129 (2017).
  MedlineGoogle Scholar
• 17. Alay I, Kaya C, Karaca I et al. The effect of being diagnosed with human papillomavirus infection on women's sexual lives. J. Med. Virol. 92(8), 1290–1297 (2020).
  Medline CASGoogle Scholar
• 18. Boda D, Docea AO, Calina D et al. Human papillomavirus: apprehending the link with carcinogenesis and unveiling new research avenues (Review). Int. J. Oncol. 52(3), 637–655 (2018).
  Medline CASGoogle Scholar
• 19. Prati B, Marangoni B, Boccardo E. Human papillomavirus and genome instability: from productive infection to cancer. Clinics (Sao Paulo, Brazil) 73(Suppl. 1), e539s (2018).
  MedlineGoogle Scholar
• 20. McBride AA, Warburton A. The role of integration in oncogenic progression of HPV-associated cancers. PLoS Pathogen. 13, 4 (2017).
  Google Scholar
• 21. Gupta SM, Mania-Pramanik J. Molecular mechanisms in progression of HPV-associated cervical carcinogenesis. J. Biomed. Sci. 26(1), 28 (2019).
  MedlineGoogle Scholar
• 22. Garbuglia AR, Lapa D, Sias C, Capobianchi MR, Del Porto P. The use of both therapeutic and prophylactic vaccines in the therapy of papillomavirus disease. Front. Immunol. 11, 188 (2020). • Addresses the latest updates in treatment and prevention of HPV infection.
  Medline CASGoogle Scholar
• 23. Jing Y, Wang T, Chen Z et al. Phylogeny and polymorphism in the long control regions E6, E7, and L1 of HPV Type 56 in women from southwest China. Mol. Med. Rep. 17(5), 7131–7141 (2018).
  Medline CASGoogle Scholar
• 24. Di-Domenico M, Giovane G, Kouidhi S et al. HPV epigenetic mechanisms related to oropharyngeal and cervix cancers. Cancer Biol. Ther. 19(10), 850–857 (2017).
  Google Scholar
• 25. Yeo-Teh N, Ito Y, Jha S. High-risk human papillomaviral oncogenes E6 and E7 target key cellular pathways to achieve oncogenesis. Int. J. Mol. Sci. 19(6), 1706 (2018).
  MedlineGoogle Scholar
• 26. Martinez-Zapien D, Ruiz FX, Poirson J et al. Structure of the E6/E6AP/p53 complex required for HPV-mediated degradation of p53. Nature 529(7587), 541–545 (2016).
  Medline CASGoogle Scholar
• 27. Ganti K, Broniarczyk J, Manoubi W et al. The human papillomavirus E6 PDZ binding motif: from life cycle to malignancy. Viruses 7(7), 3530–3551 (2015).
  Medline CASGoogle Scholar
• 28. Kranjec C, Tomaić V, Massimi P, Nicolaides L, Doorbar J, Banks L. The high-risk HPV E6 target scribble (hScrib) is required for HPV E6 expression in cervical tumour-derived cell lines. Papillomavirus Res. 2, 70–77 (2016).
  MedlineGoogle Scholar
• 29. Fischer M, Uxa S, Stanko C, Magin TM, Engeland K. Human papillomavirus E7 oncoprotein abrogates the p53-p21-DREAM pathway. Sci. Rep. 7(1), 2603 (2017).
  MedlineGoogle Scholar
• 30. Kgatle MM, Spearman CW, Kalla AA, Hairwadzi HN. DNA oncogenic virus-induced oxidative stress, genomic damage, and aberrant epigenetic alterations. Oxid. Med. Cell Longev. 2017, 1–16 (2017).
  Google Scholar
• 31. Pop S, Enciu AM, Tarcomnicu I et al. Phytochemicals in cancer prevention: modulating epigenetic alterations of DNA methylation. Phytochem. Rev. 18, 1005–1024 (2019).
  CASGoogle Scholar
• 32. Fang J, Zhang H, Jin S. Epigenetics and cervical cancer: from pathogenesis to therapy. Tumour Biol. 35, 5083–5093 (2014).
  Medline CASGoogle Scholar
• 33. Bennett RL, Licht JD. Targeting epigenetics in cancer. Annu. Rev. Pharmacol. Toxicol. 58(1), 187–207 (2018).
  Medline CASGoogle Scholar
• 34. Sen P, Ganguly P, Ganguly N. Modulation of DNA methylation by human papillomavirus E6 and E7 oncoproteins in cervical cancer. Oncol. Lett. 15(1), 11–22 (2018).
  MedlineGoogle Scholar
• 35. Stability RW. Stability and flexibility of epigenetic gene regulation in mammalian development. Nature 24(447), 7143 (2007).
  Google Scholar
• 36. Okano M, Bell DW, Haber DA, Li E. DNA methyltransferases Dnmt3a LED. and Dnmt3b are essential for de novo methylation and mammalian development. Cell 29(99), 3 (1999).
  Google Scholar
• 37. Ooi SK, Qiu C, Bernstein E et al. DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA. Nature 9(448), 7154 (2007).
  Google Scholar
• 38. Arora I, Sharma M, Tollefsbol TO. Combinatorial epigenetics impact of polyphenols and phytochemicals in cancer prevention and therapy. Int. J. Mol. Sci. 20(18), 4567 (2019).
  Medline CASGoogle Scholar
• 39. Sundaram MK, Unni S, Somvanshi P et al. Genistein modulates signaling pathways and targets several epigenetic markers in HeLa cells. Genes 10(12), 955 (2019).
  Medline CASGoogle Scholar
• 40. Nebbioso A, Tambaro FP, Dell'Aversana C, Altucci L. Cancer epigenetics: moving forward. PLOS Genet. 14, 6 (2018).
  Google Scholar
• 41. Yang Q, Yang Y, Zhou N et al. Epigenetics in ovarian cancer: premise, properties, and perspectives. Mol. Cancer 17(1), 1–21 (2018).
  MedlineGoogle Scholar
• 42. Shukla S, Meeran SM, Katiyar SK. Epigenetic regulation by selected dietary phytochemicals in cancer chemoprevention. Cancer Lett. 355(1), 9–17 (2014).
  Medline CASGoogle Scholar
• 43. Kaufman-Szymczyk A, Majewski G, Lubecka-Pietruszewska K, Fabianowska-Majewska K. The role of sulforaphane in epigenetic mechanisms, including interdependence between histone modification and DNA methylation. Int. J. Mol. Sci. 16(12), 29732–29743 (2015).
  Medline CASGoogle Scholar
• 44. Sanaei M, Kavoosi F. Histone deacetylases and histone deacetylase inhibitors: molecular mechanisms of action in various cancers. Adv. Biomed. Res. 8, 63 (2019).
  Medline CASGoogle Scholar
• 45. Fernandes J, Acuña SM, Aoki JI, Floeter-Winter LM, Muxel SM. Long non-coding RNAs in the regulation of gene expression: physiology and disease. Noncoding RNA 5(1), 17 (2019).
  Medline CASGoogle Scholar
• 46. Oliveto S, Mancino M, Manfrini N, Biffo S. Role of microRNAs in translation regulation and cancer. World J. Biol. Chem. 8(1), 45–56 (2017).
  MedlineGoogle Scholar
• 47. Michlewski G, Cáceres JF. Post-transcriptional control of miRNA biogenesis. RNA (New York, NY) 25(1), 1–16 (2019).
  Medline CASGoogle Scholar
• 48. Pardini B, De Maria D, Francavilla A, Di Gaetano C, Ronco G, Naccarati A. MicroRNAs as markers of progression in cervical cancer: a systematic review. BMC Cancer 18, 1 (2018).
  MedlineGoogle Scholar
• 49. Svoronos AA, Engelman DM, Slack FJ. OncomiR or tumour suppressor? The duplicity of MicroRNAs in cancer. Cancer Res. 76(13), 3666–3670 (2016).
  Medline CASGoogle Scholar
• 50. miRBase: the microRNA database. https://mirbase.org/
  Google Scholar
• 51. Kamińska K, Nalejska E, Kubiak M et al. Prognostic and predictive epigenetic biomarkers in oncology. Mol. Diagn. Ther. 23(1), 83–95 (2019).
  Medline CASGoogle Scholar
• 52. Durzynska J, Lesniewicz K, Poreba E. Human papillomaviruses in epigenetic regulations. Mutat. Res. Mutat. Res. 772, 36–50 (2017).
  Medline CASGoogle Scholar
• 53. Do H, Kim W. Roles of oncogenic long non-coding RNAs in cancer development. Genomics Informat. 16, 4 (2018).
  Google Scholar
• 54. Dong J, Su M, Chang W, Zhang K, Wu S, Xu T. Long non-coding RNAs on the stage of cervical cancer (Review). Oncol. Rep. 38, 1923–1931 (2017).
  Medline CASGoogle Scholar
• 55. Li B, Li B. The role of lncRNAs in the development of endometrial carcinoma (Review). Oncol. Lett. 16, 3424–3429 (2018).
  MedlineGoogle Scholar
• 56. Zhang X, Mao L, Li L, He Z, Wang N, Song Y. Long noncoding RNA GIHCG functions as an oncogene and serves as a serum diagnostic biomarker for cervical cancer. J. Cancer 10(3), 672–681 (2019).
  Medline CASGoogle Scholar
• 57. Alfaro-Mora Y, Herrera LA, Cáceres-Gutiérrez R, Andonegui-Elguera MA, Dominguez-Gómez G, D'iaz-Chávez J. Role of Epigenetics in Cervical Cancer. Gynaecological Malignancies – Updates and Advances, IntechOpen, London, UK (2019).
  Google Scholar
• 58. Cicchini L, Westrich JA, Xu T et al. Suppression of antitumour immune responses by human papillomavirus through epigenetic downregulation of CXCL14. mBio 7(3), 216–270 (2016).
  Google Scholar
• 59. Bashaw AA, Leggatt GR, Chandra J, Tuong ZK, Frazer IH. Modulation of antigen presenting cell functions during chronic HPV infection. Papillomavirus Res. (Amsterdam, The Netherlands) 4, 58–65 (2017).
  MedlineGoogle Scholar
• 60. Landoni F, Colombo A, Milani R, Placa F, Zanagnolo V, Mangioni C. Randomized study between radical surgery and radiotherapy for the treatment of stage IB–IIA cervical cancer: 20-year update. J. Gynecol. Oncol. 28, 3 (2017).
  Google Scholar
• 61. Shim S-H, Lim MC, Kim HJ et al. Can simple trachelectomy or conization show comparable survival rate compared with radical trachelectomy in IA1 cervical cancer patients with lymphovascular space invasion who wish to save fertility? A systematic review and guideline recommendation. PLOS ONE 13, 1 (2018).
  Google Scholar
• 62. Tseng JH, Aloisi A, Sonoda Y et al. Long-term oncologic outcomes of uterine-preserving surgery in young women with stage ib1 cervical cancer. Int. J. Gynecol. Cancer 28(7), 1350–1359 (2018).
  MedlineGoogle Scholar
• 63. Ventola CL. Cancer Immunotherapy, Part 2: Efficacy, safety, and other clinical considerations. PT 42(7), 452–463 (2017).
  MedlineGoogle Scholar
• 64. Jordan K, Feyer P, H'Oller U, Link H, W'Ormann B, Jahn F. Supportive treatments for patients with cancer. Deutsches Arzteblatt Int. 114(27–28), 481–487 (2017).
  MedlineGoogle Scholar
• 65. Goktas SB, Gun I, Yildiz T, Sakar MN, Caglayan S. The effect of total hysterectomy on sexual function and depression. Pakistan J. Med. Sci. 31(3), 700–705 (2015).
  MedlineGoogle Scholar
• 66. Pfaendler KS, Tewari KS. Changing paradigms in the systemic treatment of advanced cervical cancer. Am. J. Obstet. Gynecol. 214(1), 2 (2016).
  Google Scholar
• 67. Cho O, Chun M. Management for locally advanced cervical cancer: new trends and controversial issues. Radiat. Oncol. J. 36(4), 254–264 (2018).
  MedlineGoogle Scholar
• 68. Mishra GA, Pimple SA, Shastri SS. An overview of prevention and early detection of cervical cancers. Indian J. Med. Paediatr. Oncol. 32(3), 125–132 (2011).
  MedlineGoogle Scholar
• 69. Baylin SB, Jones PA. Epigenetic determinants of cancer. Cold Spring Harbor Persp.Biol. 8, 9 (2016).
  Google Scholar
• 70. Suraweera A, O'Byrne KJ, Richard DJ. Combination therapy with histone deacetylase inhibitors (HDACi) for the treatment of cancer: achieving the full therapeutic potential of HDACi. Front. Oncol. 8, 92 (2018).
  MedlineGoogle Scholar
• 71. Martin SL, Royston KJ, Tollefsbol TO. The Role of Non-Coding RNAs and Isothiocyanates in Cancer. Mol. Nutr. Food Res. 62, 18 (2018).
  Google Scholar
• 72. Ribeiro ML, Reyes-Garau D, Armengol M, Fernández-Serrano M, Roué G. Recent advances in the targeting of epigenetic regulators in B-cell non-Hodgkin lymphoma. Front. Genet. 10, 986 (2019).
  Medline CASGoogle Scholar
• 73. Kronfol MM, Dozmorov MG, Huang R, Slattum PW, McClay JL. The role of epigenomics in personalized medicine. Expert Rev. Prec. Med. Drug Dev. 2(1), 33–45 (2017).
  MedlineGoogle Scholar
• 74. Greenwell M, Rahman PK. Medicinal plants: their use in anticancer treatment. Int. J. Pharmaceut. Sci. Res. 6(10), 4103–4112 (2015).
  Medline CASGoogle Scholar
• 75. Barbieri R, Coppo E, Marchese A et al. Phytochemicals for human disease: an update on plant-derived compounds antibacterial activity. Microbiol. Res. 196, 44–68 (2017).
  Medline CASGoogle Scholar
• 76. Karimi A, Majlesi M, Rafieian-Kopaei M. Herbal versus synthetic drugs; beliefs and facts. J. Nephropharmacol. 4(1), 27–30 (2015).
  Medline CASGoogle Scholar
• 77. Kapinova A, Kubatka P, Golubnitschaja O et al. Dietary phytochemicals in breast cancer research: anticancer effects and potential utility for effective chemoprevention. Environ. Health Prev. Med. 23(1), 36 (2018).
  Medline CASGoogle Scholar
• 78. Sharma SB, Gupta R. Drug development from natural resource: a systematic approach. Mini Rev. Med. Chem. 1(15), 1 (2015).
  Google Scholar
• 79. Anwar-Mohamed A, El-Kadi AOS. Sulforaphane induces CYP1A1 mRNA, protein, and catalytic activity levels via an AhR-dependent pathway in murine hepatoma Hepa 1c1c7 and human HepG2 cells. Cancer Lett. 8(275), 1 (2009).
  Google Scholar
• 80. Khan A, Sundaram MK, Hamza A et al. Sulforaphane reverses the expression of various tumour suppressor genes by targeting DNMT3B and HDAC1 in human cervical cancer cells. Evidence-Based Complement. Altern. Med. 2015, 412149 (2015).
  Google Scholar
• 81. Su X, Jiang X, Meng L, Dong X, Shen Y, Xin Y. Anticancer activity of sulforaphane: the epigenetic mechanisms and the Nrf2 signaling pathway. Oxid. Med. Cell Longev. 2018, 1–10 (2018).
  Google Scholar
• 82. Zaman MS, Chauhan N, Yallapu MM et al. Curcumin nanoformulation for cervical cancer treatment. Sci. Rep. 6, 20051 (2016).
  Medline CASGoogle Scholar
• 83. Thakur VS, Deb G, Babcook MA et al. Plant phytochemicals as epigenetic modulators: role in cancer chemoprevention. AAPS J. 16, 151–163 (2014).
  Medline CASGoogle Scholar
• 84. Kumar D, Basu S, Parija L et al. Curcumin and ellagic acid synergistically induce ROS generation, DNA damage, p53 accumulation and apoptosis in HeLa cervical carcinoma cells. Biomed. Pharmacother. 81, 31–37 (2016).
  Medline CASGoogle Scholar
• 85. Kim E, Bisson WH, L'Ohr CV et al. Histone and non-histone targets of dietary deacetylase inhibitors. Curr. Topics Med. Chem. 16(7), 714–731 (2016).
  Medline CASGoogle Scholar
• 86. Guo H, Zhang D, Fu Q. Inhibition of cervical cancer by promoting IGFBP7 expression using ellagic acid from pomegranate peel. Med. Sci. Monit. 22, 4881–4886 (2016).
  Medline CASGoogle Scholar
• 87. Tuli HS, Tuorkey MJ, Thakral F et al. Molecular mechanisms of action of genistein in cancer: recent advances. Front. Pharmacol. 10, 1336 (2019).
  Medline CASGoogle Scholar
• 88. Abotaleb M, Samuel SM, Varghese E et al. Flavonoids in cancer and apoptosis. Cancers 28, 11 (2018).
  Google Scholar
• 89. Farhan M, Ullah MF, Faisal M et al. Differential methylation and acetylation as the epigenetic basis of resveratrol's anticancer activity. Medicines (Basel, Switzerland) 6(1), 24 (2019). • Discusses the action of resveratrol as an anticancer agent. Its mechanism of action is mainly based on the epigenetic regulation, specifically through methylation and acetylation.
  Medline CASGoogle Scholar
• 90. Yu X, Liu Y, Wang Y, Mao X, Zhang Y, Xia J. Baicalein induces cervical cancer apoptosis through the NF-κB signaling pathway. Mol. Med. Rep. 17(4), 5088–5094 (2018).
  Medline CASGoogle Scholar
• 91. Clemente-Soto AF, Salas-Vidal E, Milan-Pacheco C, Sánchez-Carranza JN, Peralta-Zaragoza O, González-Maya L. Quercetin induces G2 phase arrest and apoptosis with the activation of p53 in an E6 expression-independent manner in HPV-positive human cervical cancer-derived cells. Mol. Med. Reports 1(19), 3 (2019).
  Google Scholar
• 92. Sundaram MK, Hussain A, Haque S, Raina R, Afroze N. Quercetin modifies 5′CpG promoter methylation and reactivates various tumour suppressor genes by modulating epigenetic marks in human cervical cancer cells. J. Cell. Biochem. 120(10), 18357–18369 (2019).
  MedlineGoogle Scholar
• 93. Palliyaguru DL, Yuan JM, Kensler TW, Fahey JW. Isothiocyanates: translating the power of plants to people. Mol. Nutr. Food Res. 62, 18 (2018).
  Google Scholar
• 94. Mokhtari RB, Narges Baluch N, Homayouni TS et al. The role of sulforaphane in cancer chemoprevention and health benefits: a mini-review. J. Cell Comm. Signal. 12(1), 91–101 (2018).
  MedlineGoogle Scholar
• 95. Jiang X, Liu Y, Ma L et al. Chemopreventive activity of sulforaphane. Drug design. Dev. Ther. 12, 2905–2913 (2018).
  Medline CASGoogle Scholar
• 96. Cheng YM, Tsai CC, Hsu YC. Sulforaphane, a dietary isothiocyanate, induces G₂/M arrest in cervical cancer cells through CyclinB1 downregulation and GADD45β/CDC2 association. Int. J. Mol. Sci. 17, 9 (2016).
  Google Scholar
• 97. Sharma C, Sadrieh L, Priyani A, Ahmed M, Hassan AH, Hussain A. Anti-carcinogenic effects of sulforaphane in association with its apoptosis-inducing and anti-inflammatory properties in human cervical cancer cells. Cancer Epidemiol. 1(35), 3 (2011).
  Google Scholar
• 98. Park SY, Kim GY, Bae SJ, Yoo YH, Choi YH. Induction of apoptosis by isothiocyanate sulforaphane in human cervical carcinoma HeLa and hepatocarcinoma HepG2 cells through activation of caspase-3. Oncol. Reports 1(18), 1 (2007).
  Google Scholar
• 99. Schnekenburger M, Diederich M. Nutritional epigenetic regulators in the field of cancer. Epigenetic Cancer Ther. 2015, 393–425 (2015).
  Google Scholar
• 100. Wang S, Wang Y, Liu X, Yang Y, Wu S, Sfn LY. SFN enhanced the radiosensitivity of cervical cancer cells via activating LATS2 and blocking Rad51/MDC1 recruitment to DNA damage site. Cancers 8, 14 (2022).
  Google Scholar
• 101. Woodward KA, Draijer R, Thijssen DHJ, Low DA. Polyphenols and microvascular function in humans: a systematic review. Curr. Pharm. Des. 24(2), 203–226 (2018).
  Medline CASGoogle Scholar
• 102. Sundaram MK, Ansari MZ, Al Mutery A et al. Genistein induces alterations of epigenetic modulatory signatures in human cervical cancer cells. Anticancer Agents Med. Chem. 2018(18), 412–421 (2018).
  Google Scholar
• 103. Hassan FU, Rehman MS, Khan MS et al. Curcumin as an alternative epigenetic modulator: mechanism of action and potential effects. Front. Genet. 4, 10 (2019).
  Google Scholar
• 104. Lewinska A, Adamczyk J, Pajak J et al. Curcumin-mediated decrease in the expression of nucleolar organizer regions in cervical cancer (HeLa) cells. Mutat. Res. Toxicol. Environ. Mutagen. 771, 43–52 (2014).
  Medline CASGoogle Scholar
• 105. Khojaste E, Ahmadizadeh C. Catechin metabolites along with curcumin inhibit proliferation and induce apoptosis in cervical cancer cells by regulating VEGF expression in-vitro. Nutr. Cancer 24(74), 3 (2022).
  Google Scholar
• 106. Wang T, Wu X, Song Y, Cheng H. Curcumin induces G2/M arrest and triggers autophagy, ROS generation and cell senescence in cervical cancer cells. J. Cancer 11, 22 (2020).
  Google Scholar
• 107. Zhao X, Zhang R, Song Z et al. Curcumin suppressed the proliferation and apoptosis of HPV-positive cervical cancer cells by directly targeting the E6 protein. Phyther. Res. doi: 10.1002/ptr.7868 (2023). (Epub ahead of print). •• Address the effect of curcumin on HPV-positive cervical cancer cells. Curcumin is a antiapoptotic phytochemical with much potential regarding therapeutic effects on several diseases.
  Google Scholar
• 108. Ismail T, Calcabrini C, Diaz AR et al. Ellagitannins in cancer chemoprevention and therapy. Toxins 8(5), 151 (2016).
  MedlineGoogle Scholar
• 109. Khiewkamrop P, Phunsomboon P, Richert L et al. E catechins. EGCG and EC facilitate apoptosis induction through targeting de novo lipogenesis pathway in HepG2 cells. Cancer Cell Int. 18, 46 (2018).
  MedlineGoogle Scholar
• 110. Wang Y-Q, Lu J-L, Liang Y-R, Li Q-S. Suppressive effects of EGCG on cervical cancer. Molecules 23(9), 2334 (2018).
  MedlineGoogle Scholar
• 111. Alshatwi AA, Periasamy VS, Athinarayanan J, Elango R. Synergistic anticancer activity of dietary tea polyphenols and bleomycin hydrochloride in human cervical cancer cell: caspase-dependent and independent apoptotic pathways. Chem. Biol. Interact. 247, 1–10 (2016).
  Medline CASGoogle Scholar
• 112. Qiao Y, Cao J, Xie L, Shi X. Cell growth inhibition and gene expression regulation by (-)-epigallocatechin-3-gallate in human cervical cancer cells. Arch. Pharmacal Res. 32, 1309–1315 (2009).
  Medline CASGoogle Scholar
• 113. Asif Siddiqui F, Naim M, Islam N. Apoptotic effect of green tea polyphenol (EGCG) on cervical carcinoma cells. Diagn. Cytopathol. 39(7), 482–488 (2011).
  MedlineGoogle Scholar
• 114. Montgomery M, Srinivasan A. Epigenetic gene regulation by dietary compounds in cancer prevention. Adv. Nutr. 10(6), 1012–1028 (2019).
  MedlineGoogle Scholar
• 115. Sundaram MK, Haque S, Somvanshi P, Bhardwaj T, Hussain A. Epigallocatechin gallate inhibits HeLa cells by modulation of epigenetics and signaling pathways. 3 Biotech. 10(11), 484 (2020).
  MedlineGoogle Scholar
• 116. Zhu Y, Huang Y, Liu M et al. Epigallocatechin gallate inhibits cell growth and regulates miRNA expression in cervical carcinoma cell lines infected with different high-risk human papillomavirus subtypes. Exp. Ther. Med. 1(17), 3 (2019). • Highlights the anticancer action of epigallocatechin gallate on cervical cancer through epigenetic regulation mechanisms. Epigallocatechin gallate is one of the most important phytochemicals in targeting cervical cancer.
  Google Scholar
• 117. Kř\'\ižová L, Dadáková K, Kašparovská J, Kašparovský T. Isoflavones. Molecules (Basel, Switzerland) 24(6), 1076 (2019).
  MedlineGoogle Scholar
• 118. Hajialyani M, Farzaei MH, Echeverría J et al. Hesperidin as a neuroprotective agent: a review of animal and clinical evidence. Molecules (Basel, Switzerland) 24(3), 648 (2019).
  Medline CASGoogle Scholar
• 119. Panche AN, Diwan AD, Chandra SR. Flavonoids: an overview. J. Nutr. Sci. 5, e47 (2016).
  Medline CASGoogle Scholar
• 120. Cirmi S, Ferlazzo N, Lombardo GE et al. Chemopreventive agents and inhibitors of cancer hallmarks: may citrus offer new perspectives?. Nutrients 8(11), 698 (2016).
  MedlineGoogle Scholar
• 121. Pandey P, Khan F, Maurya P. Targeting Jab1 using hesperidin (dietary phytocompound) for inducing apoptosis in HeLa cervical cancer cells. J. Food Biochem. 45, 7 (2021).
  Google Scholar
• 122. Abu-Amero KK, Kondkar AA, Chalam KV. Resveratrol and ophthalmic diseases. Nutrients 8(4), 200 (2016).
  MedlineGoogle Scholar
• 123. Salehi B, Mishra AP, Nigam M et al. Resveratrol: a double-edged sword in health benefits. Biomedicines 6(3), 91 (2018).
  Medline CASGoogle Scholar
• 124. Resveratrol RG. Multiple activities on the biological functionality of the cell. Nutraceuticals 1, 453–464 (2016).
  Google Scholar
• 125. Ko JH, Sethi G, Um JY et al. The role of resveratrol in cancer therapy. Int. J. Mol. Sci. 18(12), 2589 (2017).
  MedlineGoogle Scholar
• 126. Saghafi T, Taheri RA, Parkkila S, Emameh RZ. Phytochemicals as modulators of long non-coding RNAs and inhibitors of cancer-related carbonic anhydrases. Int. J. Mol. Sci. 20(12), 2939 (2019).
  Medline CASGoogle Scholar
• 127. Zhang P, Li H, Yang B et al. Biological significance and therapeutic implication of resveratrol-inhibited Wnt, Notch and STAT3 signaling in cervical cancer cells. Genes Cancer 5, 5–6 (2014).
  Google Scholar
• 128. Saenglee S, Jogloy S, Patanothai A, Leid M, Senawong T. Cytotoxic effects of peanut phenolics possessing histone deacetylase inhibitory activity in breast and cervical cancer cell lines. Pharmacol. Reports 68, 1102–1110 (2016).
  CASGoogle Scholar
• 129. Liu Z, Li Y, She G et al. Resveratrol induces cervical cancer HeLa cell apoptosis through the activation and nuclear translocation promotion of FOXO3a. Die. Pharm. Int. J. Pharm. Sci. 1(75), 6 (2020).
  Google Scholar
• 130. Jiang B, Tian Q, Shu C, Zhao J, Xue M, Zhu S. Resveratrol enhances the anti-cancer effects of cis-platinum on human cervical cancer cell lines by activating the SIRT3 relative anti-oxidative pathway. Front. Pharmacol. 5, 13 (2022).
  Google Scholar
• 131. Li L, Qiu RL, Lin Y et al. Resveratrol suppresses human cervical carcinoma cell proliferation and elevates apoptosis via the mitochondrial and p53 signaling pathways. Oncol. Lett. 1(15), 6 (2018).
  CASGoogle Scholar
• 132. Chen RJ, Kuo HC, Cheng LH et al. Apoptotic and nonapoptotic activities of pterostilbene against cancer. Int. J. Mol. Sci. 18, 19 (2018).
  Google Scholar
• 133. Asensi M, Medina I, Ortega A et al. Inhibition of cancer growth by resveratrol is related to its low bioavailability. Free Radic. Biol. Med. 1(33), 3 (2002).
  Google Scholar
• 134. Chatterjee K, AlSharif D, Mazza C, Syar P, Al Sharif M, Fata JE. Resveratrol and pterostilbene exhibit anticancer properties involving the downregulation of HPV oncoprotein E6 in cervical cancer cells. Nutrients 21, 10 (2018).
  Google Scholar
• 135. Shin HJ, Han JM, Choi YS, Jung HJ. Pterostilbene suppresses both cancer cells and cancer stem-like cells in cervical cancer with superior bioavailability to resveratrol. Molecules 6, 25 (2020).
  Google Scholar
• 136. Kim YJ, Kim HJ, Lee JY, Kim DH, Kang MS, Park W. Anti-inflammatory effect of baicalein on polyinosinic-polycytidylic acid-induced RAW 264.7 mouse macrophages. Viruses 10(5), 224 (2018).
  MedlineGoogle Scholar
• 137. Liao C-Y, Lee C-C, Tsai C et al. Novel investigations of flavonoids as chemopreventive agents for hepatocellular carcinoma. Biomed. Res. Int. 2015(4), 1–26 (2015).
  Google Scholar
• 138. Yu X, Yang Y, Li Y et al. Baicalein inhibits cervical cancer progression via downregulating long noncoding RNA BDLNR and its downstream PI3 K/Akt pathway. Int. J. Biochem. Cell Biol. 94, 107–118 (2018).
  Medline CASGoogle Scholar
• 139. Yang J, Nie J, Ma X et al. Targeting PI3K in cancer: mechanisms and advances in clinical trials. Mol. Cancer 18, 26 (2019).
  MedlineGoogle Scholar
• 140. Lei H, Shi J, Teng Y et al. Baicalein modulates the radiosensitivity of cervical cancer cells in vitro via miR-183 and the JAK2/STAT3 signaling pathway. Adv. Clin. Exp. Med. 30(7), 727–736 (2021). •• Baicalein is an important phytochemical in therapy of cervical cancer, mainly related to its role in combination therapy. This reference discuss the role of baicalein in enhancing the radiosesntivity of cervical cancer cells through modulating miR-183 expression.
  MedlineGoogle Scholar
• 141. Wu X, Yang Z, Dang H, Peng H, Dai Z. Baicalein inhibits the proliferation of cervical cancer cells through the GSK3β-dependent pathway. Oncol. Res. Featur. Preclin. Clin. Cancer Ther. 7(26), 4 (2018).
  CASGoogle Scholar
• 142. Xia X, Xia J, Yang H et al. Baicalein blocked cervical carcinoma cell proliferation by targeting CCND1 via Wnt/β-catenin signaling pathway. Artif. Cell, Nanomed. Biotechnol. 4(47), 1 (2019).
  Google Scholar
• 143. Yu X, Lu K, Xia J, Mao X. Baicalein induces HeLa cell growth inhibition by down-regulation of matrix metalloproteinases and activating extracellular signal-regulated kinase. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi: Chinese J. Cell Mol. Immunol. 1(30), 8 (2014).
  Google Scholar
• 144. David AVA, Arulmoli R, Parasuraman S. Overviews of biological importance of quercetin: a bioactive flavonoid. Pharmaco. Rev. 10(20), 84–89 (2016).
  Medline CASGoogle Scholar
• 145. Shafabakhsh R, Asemi Z. Quercetin: a natural compound for ovarian cancer treatment. J. Ovarian Res. 12, 55 (2019).
  MedlineGoogle Scholar
• 146. Hashemzaei M, Far AD, Yari A et al. Anticancer and apoptosis-inducing effects of quercetin in vitro and in vivo. Oncol. Rep. 38(2), 819–828 (2017).
  Medline CASGoogle Scholar
• 147. Alvarez MC, Maso V, Torello CO et al. The polyphenol quercetin induces cell death in leukemia by targeting epigenetic regulators of pro-apoptotic genes. Clin. Epigenet 10, 139 (2018).
  MedlineGoogle Scholar
• 148. Fernández-Palanca P, Fondevila F, Méndez-Blanco C, Tuñón MJ, González-Gallego J, Mauriz JL. Antitumor effects of quercetin in hepatocarcinoma in vitro and in vivo models: a systematic review. Nutrients 11, 12 (2019).
  Google Scholar
• 149. He C, Lu X, Li J et al. The effect of quercetin on cervical cancer cells as determined by inducing tumor endoplasmic reticulum stress and apoptosis and its mechanism of action. Am. J. Transl. Res. 13, 5 (2021).
  Google Scholar
• 150. Murata M, Komatsu S, Miyamoto E et al. Quercetin up-regulates the expression of tumor-suppressive microRNAs in human cervical cancer. Biosci. Microbiota, Food Heal. 42(1), 87–93 (2023). •• Addresses the effect of quercetin on expression of different miRNAs in cervical cancer. Quercetin is a very well-known phytochemical with anti-inflammatory effects on different range of diseases.
  Medline CASGoogle Scholar
• 151. Chan CW, Deadman BJ, Manley-Harris M, Wilkins AL, Alber DG, Harry E. Analysis of the flavonoid component of bioactive New Zealand mānuka (Leptospermum scoparium) honey and the isolation, characterisation and synthesis of an unusual pyrrole. Food Chem. 141(3), 1772–1781 (2013).
  Medline CASGoogle Scholar
• 152. Woźniak M, Mrówczyńska L, Kwaśniewska-Sip P, Waśkiewicz A, Nowak P, Ratajczak I. Effect of the solvent on propolis phenolic profile and its antifungal, antioxidant, and in vitro cytoprotective activity in human erythrocytes under oxidative stress. Molecules 17, 25 (2020).
  Google Scholar
• 153. Batra P, Sharma AK. Anti-cancer potential of flavonoids: recent trends and future perspectives. 3 Biotech. 3(6), 439–459 (2013).
  MedlineGoogle Scholar
• 154. Pal-Bhadra M, Ramaiah MJ, Reddy TL et al. Plant HDAC inhibitor chrysin arrest cell growth and induce p21 WAF1 by altering chromatin of STAT response element in A375 cells. BMC Cancer 12, 1–7 (2012).
  MedlineGoogle Scholar
• 155. Pawar JS, Mustafa S, Chrysin GI. Chrysin and capsaicin induces premature senescence and apoptosis via mitochondrial dysfunction and p53 elevation in cervical cancer cells. Saudi J. Biol. Sci. 1(29), 5 (2022).
  Google Scholar
• 156. Laishram S, Moirangthem DS, Borah JC et al. Chrysin rich Scutellaria discolor Colebr. induces cervical cancer cell death via the induction of cell cycle arrest and caspase-dependent apoptosis. Life Sci. 15(143), 105–113 (2015).
  Google Scholar
• 157. Raina R, Afroze N, Sundaram MK et al. Chrysin inhibits propagation of HeLa cells by attenuating cell survival and inducing apoptotic pathways. Eur. Rev. Med. Pharmacol. Sci. 1(25), 5 (2021). •• Chrysin is an interesting phytochemical that has received increased attention lately. This reference discuss its role in inducing apoptosis in cervical cancer.
  Google Scholar
• 158. Yu Y, Zick S, Li X, Zou P, Wright B, Sun D. Examination of the pharmacokinetics of active ingredients of ginger in humans. AAPS J. 13, 417–426 (2011).
  Medline CASGoogle Scholar
• 159. Wang W, Li CY, Wen XD, Li P, Wi L-W. Simultaneous determination of 6-gingerol, 8-gingerol, 10-gingerol and 6-shogaol in rat plasma by liquid chromatography–mass spectrometry: application to pharmacokinetics. J. Chromatogr. B. 15(877), 671–679 (2009).
  CASGoogle Scholar
• 160. Oyagbemi AA, Saba AB, Azeez OI. Molecular targets of [6]-gingerol: Its potential roles in cancer chemoprevention. Biofactors 36(3), 169–178 (2010).
  Medline CASGoogle Scholar
• 161. Rastogi N, Duggal S, Singh SK et al. Proteasome inhibition mediates p53 reactivation and anti-cancer activity of 6-gingerol in cervical cancer cells. Oncotarget 12, 6 (2015).
  Google Scholar
• 162. Liu Y, Whelan RJ, Pattnaik BR et al. Terpenoids from Zingiber officinale (ginger) induce apoptosis in endometrial cancer cells through the activation of p53. PLOS ONE 31, 7 (2012).
  Google Scholar
• 163. Rastogi N, Gara RK, Trivedi R et al. (6)-Gingerolinduced myeloid leukemia cell death is initiated by reactive oxygen species and activation of miR-27b expression. Free Radic. Biol. Med. 1(68), 288–301 (2014).
  Google Scholar
• 164. Lv C, Hong Y, Miao L et al. Wentilactone A as a novel potential antitumor agent induces apoptosis and G2/M arrest of human lung carcinoma cells, and is mediated by HRas-GTP accumulation to excessively activate the Ras/Raf/ERK/p53-p21 pathway. Cell Death Dis. 4, 12 (2013).
  Google Scholar
• 165. Zhang F, Zhang JG, Qu J, Zhang Q, Prasad C, Wei Z-J. Assessment of anti-cancerous potential of 6-gingerol (Tongling white ginger) and its synergy with drugs on human cervical adenocarcinoma cells. Food Chem. Toxicol. 1(109), 910–922 (2017).
  Google Scholar
• 166. Ahmed SH, Gonda T, Hunyadi A. Medicinal chemistry inspired by ginger: exploring the chemical space around 6-gingerol. RSC Adv. 11(43), 26687–26699 (2021).
  Medline CASGoogle Scholar
• 167. Liu Q, Peng YB, Qi LW et al. The cytotoxicity mechanism of 6-shogaol-treated HeLa human cervical cancer cells revealed by label-free shotgun proteomics and bioinformatics analysis. Evid. Based Complement. Altern. Med. 1, 2012 (2012).
  Google Scholar
• 168. Pei XD, He ZL, Yao HL et al. 6-Shogaol from ginger shows anti-tumor effect in cervical carcinoma via PI3K/Akt/mTOR pathway. Eur. J. Nutr. 1, 1–3 (2021).
  Google Scholar
• 169. Wei QY, He KM, Chen JL, Xu YM, Lau A. Phytofabrication of nanoparticles as novel drugs for anticancer applications. Molecules (Basel, Switzerland) 24(23), 4246 (2019).
  Medline CASGoogle Scholar
• 170. Altemimi A, Lakhssassi N, Baharlouei A, Watson DG, Lightfoot DA. Phytochemicals: extraction, isolation, and identification of bioactive compounds from plant extracts. Plants (Basel, Switzerland) 6(4), 42 (2017).
  MedlineGoogle Scholar
• 171. Bode AM, Dong Z. Toxic phytochemicals and their potential risks for human cancer. Cancer Prev. Res. (Philadelphia, PA) 8(1), 1–8 (2015).
  Medline CASGoogle Scholar