DOI QR코드

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Characteristic Features of Cytotoxic Activity of Flavonoids on Human Cervical Cancer Cells

  • Sak, Katrin (NGO Praeventio)
  • Published : 2014.10.23

Abstract

Cervical cancer is the most common gynecologic malignancy worldwide and development of new therapeutic strategies and anticancer agents is an urgent priority. Plants have remained an important source in the search for novel cytotoxic compounds and several polyphenolic flavonoids possess antitumor properties. In this review article, data about potential anticarcinogenic activity of common natural flavonoids on various human cervical cancer cell lines are compiled and analyzed showing perspectives for the use of these secondary metabolites in the treatment of cervical carcinoma as well as in the development of novel chemotherapeutic drugs. Such anticancer effects of flavonoids seem to differentially depend on the cellular type and origin of cervical carcinoma creating possibilities for specific targeting in the future. Besides the cytotoxic activity per se, several flavonoids can also contribute to the increase in efficacy of conventional therapies rendering tumor cells more sensitive to standard chemotherapeutics and irradiation. Although the current knowledge is still rather scarce and further studies are certainly needed, it is clear that natural flavonoids may have a great potential to benefit cervical cancer patients.

Keywords

Cervical cancer;natural flavonoids;anticancer mechanisms;chemosensitization

Acknowledgement

Supported by : NGO Praeventio

References

  1. Alshatwi AA, Ramesh E, Periasamy VS, Subash-Babu P (2013). The apoptotic effect of hesperetin on human cervical cancer cells is mediated through cell cycle arrest, death receptor, and mitochondrial pathways. Fundam Clin Pharmacol, 27, 581-92. https://doi.org/10.1111/j.1472-8206.2012.01061.x
  2. Ahn WS, Huh SW, Bae SM, et al (2003a). A major constituent of green tea, EGCG, inhibits the growth of a human cervical cancer cell line, CaSki cells, through apoptosis, G(1) arrest, and regulation of gene expression. DNA Cell Biol, 22, 217-24. https://doi.org/10.1089/104454903321655846
  3. Ahn WS, Yoo J, Huh SW, et al (2003b). Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions. Eur J Cancer Prev, 12, 383-90. https://doi.org/10.1097/00008469-200310000-00007
  4. Al-Hazzani AA, Alshatwi AA (2011). Catechin hydrate inhibits proliferation and mediates apoptosis of SiHa human cervical cancer cells. Food Chem Toxicol, 49, 3281-6. https://doi.org/10.1016/j.fct.2011.09.023
  5. Alonso-Castro AJ, Ortiz-Sanchez E, Garcia-Regalado A, et al (2013). Kaempferitrin induces apoptosis via intrinsic pathway in HeLa cells and exerts antitumor effects. J Ethnopharmacol, 145, 476-89. https://doi.org/10.1016/j.jep.2012.11.016
  6. Bazzaro M, Anchoori RK, Mudiam MK, et al (2011). ${\alpha}$,${\beta}$- Unsaturated carbonyl system of chalcone-based derivatives is responsible for broad inhibition of proteasomal activity and preferential killing of human papilloma virus (HPV) positive cervical cancer cells. J Med Chem, 54, 449-56. https://doi.org/10.1021/jm100589p
  7. Butler LM, Wu AH (2011). Green and black tea in relation to gynecologic cancers. Mol Nutr Food Res, 55, 931-40. https://doi.org/10.1002/mnfr.201100058
  8. Bhatia N, Zhao J, Wolf DM, Agarwal R (1999). Inhibition of human carcinoma cell growth and DNA synthesis by silibinin, an active constituent of milk thistle: comparison with silymarin. Cancer Lett, 147, 77-84. https://doi.org/10.1016/S0304-3835(99)00276-1
  9. Bishayee K, Ghosh S, Mukherjee A, et al (2013). Quercetin induces cytochrome-c release and ROS accumulation to promote apoptosis and arrest the cell cycle in G2/M, in cervical carcinoma: signal cascade and drug-DNA interaction. Cell Prolif, 46, 153-63. https://doi.org/10.1111/cpr.12017
  10. Borska S, Gebarowska E, Wysocka T, Drag-Zalesinska M, Zabel M (2003). Induction of apoptosis by EGCG in selected tumour cell lines in vitro. Folia Histochem Cytobiol, 41, 229-32.
  11. Cardenas M, Marder M, Blanck VC, Roguin LP (2006). Antitumor activity of some natural flavonoids and synthetic derivatives on various human and murine cancer cell lines. Bioorg Med Chem, 14, 2966-71. https://doi.org/10.1016/j.bmc.2005.12.021
  12. Chen D, Cao J, Tian L, Liu F, Sheng X (2011). Induction of apoptosis by casticin in cervical cancer cells through reactive oxygen species-mediated mitochondrial signaling pathways. Oncol Rep, 26, 1287-94.
  13. Chen YJ, Cheng YJ, Hung AC, et al (2013a). The synthetic flavonoid WYC02-9 inhibits cervical cancer cell migration/ invasion and angiogenesis via MAPK14 signaling. Gynecol Oncol, 131, 734-43. https://doi.org/10.1016/j.ygyno.2013.10.012
  14. Chen YJ, Kay N, Yang JM, et al (2013b). Total synthetic protoapigenone WYC02 inhibits cervical cancer cell proliferation and tumour growth through PIK3 signalling pathway. Basic Clin Pharmacol Toxicol, 113, 8-18. https://doi.org/10.1111/bcpt.12057
  15. Cherng JM, Shieh DE, Chiang W, Chang MY, Chiang LC (2007). Chemopreventive effects of minor dietary constituents in common foods on human cancer cells. Biosci Biotechnol Biochem, 71, 1500-4. https://doi.org/10.1271/bbb.70008
  16. Csapi B, Hajdu Z, Zupko I, et al (2010). Bioactivity-guided isolation of antiproliferative compounds from Centaurea arenaria. Phytother Res, 24, 1664-9. https://doi.org/10.1002/ptr.3187
  17. Cherry JJ, Rietz A, Malinkevich A, et al (2013). Structure based identification and characterization of flavonoids that disrupt human papillomavirus-16 E6 function. PLoS One, 8, 84506. https://doi.org/10.1371/journal.pone.0084506
  18. Chou RH, Hsieh SC, Yu YL, et al (2013). Fisetin inhibits migration and invasion of human cervical cancer cells by downregulating urokinase plasminogen activator expression through suppressing the p38 MAPK-dependent NF-kB signaling pathway. PLoS One, 8, 71983. https://doi.org/10.1371/journal.pone.0071983
  19. Chung KS, Choi JH, Back NI, et al (2010). Eupafolin, a flavonoid isolated from Artemisia princeps, induced apoptosis in human cervical adenocarcinoma HeLa cells. Mol Nutr Food Res, 54, 1318-28. https://doi.org/10.1002/mnfr.200900305
  20. Csupor-Loffler B, Hajdu Z, Zupko I, et al (2009). Antiproliferative effect of flavonoids and sesquiterpenoids from Achillea millefolium s.I. on cultured human tumour cell lines. Phytother Res, 23, 672-6. https://doi.org/10.1002/ptr.2697
  21. Csupor-Loffler B, Hajdu Z, Zupko I, et al (2011). Antiproliferative constituents of the roots of Conyza canadensis. Planta Med, 77, 1183-8. https://doi.org/10.1055/s-0030-1270714
  22. Czyz J, Madeja Z, Irmer U, Korohoda W, Hulser DF (2005). Flavonoid apigenin inhibits motility and invasiveness of carcinoma cells in vitro. Int J Cancer, 114, 12-8. https://doi.org/10.1002/ijc.20620
  23. Dat NT, Binh PT, Quynh Ie TP, et al (2010). Cytotoxic prenylated flavonoid from Morus alba. Fitoterapia, 81, 1224-7. https://doi.org/10.1016/j.fitote.2010.08.006
  24. Deng X, Zhao X, Lan Z, et al (2014). Anti-tumor effects of flavonoids from the ethnic medicine Docynia delavayi (Franch.) Schneid. and its possible mechanism. J Med Food, 17, 787-94. https://doi.org/10.1089/jmf.2013.2886
  25. GLOBOCAN2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. http://globocan.iarc.fr/Default.aspx
  26. Dhandayuthapani S, Marimuthu P, Hormann V, Kumi-Diaka J, Rathinavelu A (2013). Induction of apoptosis in HeLa cells via caspase activation by resveratrol and genistein. J Med Food, 16, 139-46. https://doi.org/10.1089/jmf.2012.0141
  27. Di Domenico F, Foppoli C, Coccia R, Perluigi M (2012). Antioxidants in cervical cancer: chemopreventive and chemotherapeutic effects of polyphenols. Biochim Biophys Acta, 1822, 737-47. https://doi.org/10.1016/j.bbadis.2011.10.005
  28. Garcia FA, Cornelison T, Nuno T, et al (2014). Results of a phase II randomized, double-blind, placebo-controlled trial of polyphenon E in women with persistent high-risk HPV infection and low-grade cervical intraepithelial neoplasia. Gynecol Oncol, 132, 377-82. https://doi.org/10.1016/j.ygyno.2013.12.034
  29. Guo JM, Kang GZ, Xiao BX, Liu DH, Zhang S (2004). Effect of daidzein on cell growth, cell cycle, and telomerase activity of human cervical cancer in vitro. Int J Gynecol Cancer, 14, 882-8. https://doi.org/10.1111/j.1048-891X.2004.14525.x
  30. Ham S, Kim KH, Kwon TH, et al (2014). Luteolin induces intrinsic apoptosis via inhibition of E6/E7 oncogenes and activation of extrinsic and intrinsic signaling pathways in HPV-18-associated cells. Oncol Rep, 31, 2683-91.
  31. He F, Wang Q, Zheng XL, et al (2012). Wogonin potentiates cisplatin-induced cancer cell apoptosis through accumulation of intracellular reactive oxygen species. Oncol Rep, 28, 601-5.
  32. Hernandez BY, McDuffie K, Franke AA, Killeen J, Goodman MT (2004). Reports: plasma and dietary phytoestrogens and risk of premalignant lesions of the cervix. Nutr Cancer, 49, 109-24. https://doi.org/10.1207/s15327914nc4902_1
  33. Hirchaud F, Hermetet F, Ablise M, et al (2013). Isoliquiritigenin induces caspase-dependent apoptosis via downregulation of HPV16 E6 expression in cervical cancer CaSki cells. Planta Med, 79, 1628-35. https://doi.org/10.1055/s-0033-1350956
  34. Jakubowicz-Gil J, Paduch R, Piersiak T, et al (2005). The effect of quercetin of pro-apoptotic activity of cisplatin in HeLa cells. Biochem Pharmacol, 69, 1343-50. https://doi.org/10.1016/j.bcp.2005.01.022
  35. Hsu YL, Chia CC, Chen PJ, et al (2009). Shallot and licorice constituent isoliquiritigenin arrests cell cycle progression and induces apoptosis through the induction of ATM/p53 and initiation of the mitochondrial system in human cervical carcinoma HeLa cells. Mol Nutr Food Res, 53, 826-35. https://doi.org/10.1002/mnfr.200800288
  36. Hu T, He XW, Jiang JG, Xu XL (2014). Efficacy evaluation of a Chinese bitter tea (Ilex latifolia Thunb.) via analyses of its main components. Food Funct, 5, 876-81. https://doi.org/10.1039/c3fo60603a
  37. Hussain A, Harish G, Prabhu SA, et al (2012). Inhibitory effect of genistein on the invasive potential of human cervical cancer cells via modulation of matrix metalloproteinase-9 and tissue inhibitors of matrix metalloproteinase-1 expression. Cancer Epidemiol, 36, 387-93. https://doi.org/10.1016/j.canep.2012.07.005
  38. Jha AK, Nikbakht M, Parashar G, et al (2010). Reversal of hypermethylation and reactivation of the RAR${\beta}$2 gene by natural compounds in cervical cancer cell lines. Folia Biol (Praha), 56, 195-200.
  39. Jin YM, Xu TM, Zhao YH, Wang YC, Cui MH (2014). In vitro and in vivo anti-cancer activity of formononetin on human cervical cancer cell line HeLa. Tumour Biol, 35, 2279-84. https://doi.org/10.1007/s13277-013-1302-1
  40. Ju HK, Lee HW, Chung KS, et al (2012). Standardized flavonoidrich fraction of Artemisia princeps Pampanini cv. Sajabal induces apoptosis via mitochondrial pathway in human cervical cancer HeLa cells. J Ethnopharmacol, 141, 460-8. https://doi.org/10.1016/j.jep.2012.03.011
  41. Jung JH, Lee JO, Kim JH, et al (2010). Quercetin suppresses HeLa cell viability via AMPK-induced HSP70 and EGFR downregulation. J Cell Physiol, 223, 408-14.
  42. Kim JH, Kang JW, Kim MS, et al (2012). The apoptotic effects of the flavonoid N101-2 in human cervical cancer cells. Toxicol In Vitro, 26, 67-73. https://doi.org/10.1016/j.tiv.2011.10.012
  43. Kanno S, Tomizawa A, Hiura T, et al (2005). Inhibitory effects of naringenin on tumor growth in human cancer cell lines and sarcoma S-180-implanted mice. Biol Pharm Bull, 28, 527-30. https://doi.org/10.1248/bpb.28.527
  44. Kim EY, Kim AK (2013). Combination effect of equol and TRAIL against human cervical cancer cells. Anticancer Res, 33, 903-12.
  45. Kim H, Moon JY, Mosaddik A, Cho SK (2010). Induction of apoptosis in human cervical carcinoma HeLa cells by polymethoxylated flavone-rich Citrus grandis Osbeck (Dangyuja) leaf extract. Food Chem Toxicol, 48, 2435-42. https://doi.org/10.1016/j.fct.2010.06.006
  46. Kim MS, Bak Y, Park YS, et al (2013). Wogonin induces apoptosis by suppressing E6 and E7 expressions and activating intrinsic signaling pathways in HPV-16 cervical cancer cells. Cell Biol Toxicol, 29, 259-72. https://doi.org/10.1007/s10565-013-9251-4
  47. Kim SH, Kim SH, Kim YB, et al (2009a). Genistein inhibits cell growth by modulating various mitogen-activated protein kinases and AKT in cervical cancer cells. Ann N Y Acad Sci, 1171, 495-500. https://doi.org/10.1111/j.1749-6632.2009.04899.x
  48. Kim SH, Kim SH, Lee SC, Song YS (2009b). Involvement of both extrinsic and intrinsic apoptotic pathways in apoptosis induced by genistein in human cervical cancer cells. Ann N Y Acad Sci, 1171, 196-201. https://doi.org/10.1111/j.1749-6632.2009.04902.x
  49. Kitdamrongtham W, Manosroi A, Akazawa H, et al (2013). Potent anti-cervical cancer activity: synergistic effects of Thai medicinal plants in recipe N040 selected from the MANOSROI III database. J Ethnopharmacol, 149, 288-96. https://doi.org/10.1016/j.jep.2013.06.037
  50. Kma L (2013). Roles od plant extracts and constituents in cervical cancer therapy. Asian Pac J Cancer Prev, 14, 3429-36. https://doi.org/10.7314/APJCP.2013.14.6.3429
  51. Kuo YJ, Hwang SY, Wu MD, et al (2008). Cytotoxic constituents from Podocarpus fasciculus. Chem Pharm Bull (Tokyo), 56, 585-8. https://doi.org/10.1248/cpb.56.585
  52. Koppikar SJ, Choudhari AS, Suryavanshi SA, et al (2010). Aqueous cinnamon extract (ACE-c) from the bark of Cinnamomum cassia causes apoptosis in human cervical cancer cell line (SiHa) through loss of mitochondrial membrane potential. BMC Cancer, 10, 210. https://doi.org/10.1186/1471-2407-10-210
  53. Krifa M, Alhosin M, Muller CD, et al (2013). Limoniastrum guyonianum aqueous gall extract induces apoptosis in human cervical cancer cells involving p16 INK4A re-expression related to UHRF1 and DNMT1 down-regulation. J Exp Clin Cancer Res, 32, 30. https://doi.org/10.1186/1756-9966-32-30
  54. Kundu JK, Chun KS (2014). The promise of dried fruits in cancer chemoprevention. Asian Pac J Cancer Prev, 15, 3343-52. https://doi.org/10.7314/APJCP.2014.15.8.3343
  55. Lee HG, Yu KA, Oh WK, et al (2005). Inhibitory effect of jaceosidin isolated from Artemisiaargyi on the function of E6 and E7 oncoproteins of HPV16. J Ethnopharmacol, 98, 339-43. https://doi.org/10.1016/j.jep.2005.01.054
  56. Lee S, Kim H, Kang JW, et al (2011). The biflavonoid amentoflavone induces apoptosis via suppressing E7 expression, cell cycle arrest at sub-G1 phase, and mitochondria-emanated intrinsic pathways in human cervical cancer cells. J Med Food, 14, 808-16. https://doi.org/10.1089/jmf.2010.1428
  57. Li F, Awale S, Tezuka Y, Kadota S (2008). Cytotoxic constituents from Brazilian red propolis and their structure-activity relationship. Bioorg Med Chem, 16, 5434-40. https://doi.org/10.1016/j.bmc.2008.04.016
  58. Li F, Awale S, Tezuka Y, Kadota S (2010). Cytotoxicity of constituents from Mexican propolis against a panel of six different cancer cell lines. Nat Prod Commun, 5, 1601-6.
  59. Li HN, Nie FF, Liu W, et al (2009). Apoptosis induction of oroxylin A in human cervical cancer HeLa cell line in vitro and in vivo. Toxicology, 257, 80-5. https://doi.org/10.1016/j.tox.2008.12.011
  60. Lo YL, Wang W (2013). Formononetin potentiates epirubicininduced apoptosis via ROS production in HeLa cells in vitro. Chem Biol Interact, 205, 188-97. https://doi.org/10.1016/j.cbi.2013.07.003
  61. Lin C, Yu Y, Zhao HG, et al (2012). Combination of quercetin with radiotherapy enhances tumor radiosensitivity in vitro and in vivo. Radiother Oncol, 104, 395-400. https://doi.org/10.1016/j.radonc.2011.10.023
  62. Liu C, Wang Y, Xie S, et al (2011). Liquiritigenin induces mitochondria-mediated apoptosis via cytochrome c release and caspases activation in HeLa cells. Phytother Res, 25, 277-83.
  63. Liu Y, Xie S, Wang Y, et al (2012). Liquiritigenin inhibits tumor growth and vascularization in a mouse model of HeLa cells. Molecules, 17, 7206-16. https://doi.org/10.3390/molecules17067206
  64. Lo YL, Wang W, Ho CT (2012). 7, 3', 4'-Trihydroxyisoflavone modulates multidrug resistance transporters and induces apoptosis via production of reactive oxygen species. Toxicology, 302, 221-32. https://doi.org/10.1016/j.tox.2012.08.003
  65. Mamadalieva NZ, Herrmann F, El-Readi MZ, et al (2011). Flavonoids in Scutellaria immaculata and S. ramosissima (Lamiaceae) and their biological activity. J Pharm Pharmacol, 63, 1346-57. https://doi.org/10.1111/j.2042-7158.2011.01336.x
  66. Meiyanto E, Hermawan A, Anindyajati (2012). Natural products for cancer-targeted therapy: citrus flavonoids as potent chemopreventive agents. Asian Pac J Cancer Prev, 13, 427-36. https://doi.org/10.7314/APJCP.2012.13.2.427
  67. Moga MA, Irimie M, Oanta A, Pascu A, Burtea V (2014). Typespecific prevalence of human papillomavirus by cervical cytology among women in Brasov, Romania. Asian Pac J Cancer Prev, 15, 6887-92. https://doi.org/10.7314/APJCP.2014.15.16.6887
  68. Muthusami S, Prabakaran DS, An Z, Yu JR, Park WY (2013). EGCG suppresses Fused Toes Homolog protein through p53 in cervical cancer cells. Mol Biol Rep, 40, 5587-96. https://doi.org/10.1007/s11033-013-2660-x
  69. Papazisis KT, Kalemi TG, Zambouli D, et al (2006). Synergistic effects of protein tyrosine kinase inhibitor genistein with camptothecins against three cell lines in vitro. Cancer Lett, 233, 255-64. https://doi.org/10.1016/j.canlet.2005.03.022
  70. Noguchi M, Yokoyama M, Watanabe S, et al (2006). Inhibitory effect of the tea polyphenol, (-)-epigallocatechin gallate, on growth of cervical adenocarcinoma cell lines. Cancer Lett, 234, 135-42. https://doi.org/10.1016/j.canlet.2005.03.053
  71. Noh HJ, Sung EG, Kim JY, Lee TJ, Song IH (2010). Suppression of phorbol-12-myristate-13-acetate-induced tumor cell invasion by apigenin via the inhibition of p38 mitogen-activated protein kinase-dependent matrix metalloproteinase-9 expression. Oncol Rep, 24, 277-83.
  72. O'Prey J, Brown J, Fleming J, Harrison PR (2003). Effects of dietary flavonoids on major signal transduction pathways in human epithelial cells. Biochem Pharmacol, 66, 2075-88. https://doi.org/10.1016/j.bcp.2003.07.007
  73. Park J, Park KK, Park JH, Chung WY (2009). Isoliquiritigenin induces G2 and M phase arrest by inducing DNA damage and by inhibiting the metaphase/anaphase transition. Cancer Lett, 277, 174-81. https://doi.org/10.1016/j.canlet.2008.12.005
  74. Pluchino KM, Hall MD, Goldsborough AS, Callaghan R, Gottesman MM (2012). Collateral sensitivity as a strategy against cancer multidrug resistance. Drug Resist Updat, 15, 98-105. https://doi.org/10.1016/j.drup.2012.03.002
  75. Qiao Y, Cao J, Xie L, Shi X (2009). Cell growth inhibition and gene expression regulation by (-)-epigallocatechin-3-gallate in human cervical cancer cells. Arch Pharm Res, 32, 1309-15. https://doi.org/10.1007/s12272-009-1917-3
  76. Ramesh E, Alshatwi AA (2013). Naringin induces death receptor and mitochondria-mediated apoptosis in human cervical cancer (SiHa) cells. Food Chem Toxicol, 51, 97-105. https://doi.org/10.1016/j.fct.2012.07.033
  77. Sah JF, Balasubramanian S, Eckert RL, Rorke EA (2004). Epigallocatechin-3-gallate inhibits epidermal growth factor receptor signaling pathway. Evidence for direct inhibition of ERK1/2 and AKT kinases. J Biol Chem, 279, 12755-62. https://doi.org/10.1074/jbc.M312333200
  78. Singh M, Bhui K, Singh R, Shukla Y (2013). Tea polyphenols enhance cisplatin chemosensitivity in cervical cancer cells via induction of apoptosis. Life Sci, 93, 7-16. https://doi.org/10.1016/j.lfs.2013.02.001
  79. Samama B, Plas-Roser S, Schaeffer C, et al (2002). HPV DNA detection by in situ hybridization with catalyzed signal amplification on thin-layer cervical smears. J Histochem Cytochem, 50, 1417-20. https://doi.org/10.1177/002215540205001014
  80. Sharma C, Nusri Qel-A, Begum S, et al (2012). (-)-Epigallocatechin-3-gallate induces apoptosis and inhibits invasion and migration of human cervical cancer cells. Asian Pac J Cancer Prev, 13, 4815-22. https://doi.org/10.7314/APJCP.2012.13.9.4815
  81. Shin JI, Shim JH, Kim KH, et al (2008). Sensitization of the apoptotic effect of gamma-irradiation in genistein-pretreated CaSki cervical cancer cells. J Microbiol Biotechnol, 18, 523-31.
  82. Singh M, Tyagi S, Bhui K, Prasad S, Shukla Y (2010). Regulation of cell growth through cell cycle arrest and apoptosis in HPV 16 positive human cervical cancer cells by tea polyphenols. Invest New Drugs, 28, 216-24. https://doi.org/10.1007/s10637-009-9240-x
  83. Spoerlein C, Mahal K, Schmidt H, Schobert R (2013). Effects of chrysin, apigenin, genistein and their homoleptic copper(II) complexes on the growth and metastatic potential of cancer cells. J Inorg Biochem, 127, 107-15. https://doi.org/10.1016/j.jinorgbio.2013.07.038
  84. Thomasset SC, Berry DP, Garcea G, et al (2007). Dietary polyphenolic phytochemicals - promising cancer chemopreventive agents in humans? A review of their clinical properties. Int J Cancer, 120, 451-8. https://doi.org/10.1002/ijc.22419
  85. Totta P, Acconcia F, Leone S, Cardillo I, Marino M (2004). Mechanisms of naringenin-induced apoptotic cascade in cancer cells: involvement of estrogen receptor alpha and beta signalling. IUBMB Life, 56, 491-9. https://doi.org/10.1080/15216540400010792
  86. Tudoran O, Soritau O, Balacescu O, et al (2012). Early transcriptional pattern of angiogenesis induced by EGCG treatment in cervical tumour cells. J Cell Mol Med, 16, 520-30. https://doi.org/10.1111/j.1582-4934.2011.01346.x
  87. Wang L, Guo H, Yang L, et al (2013). Morusin inhibits human cervical cancer stem cell growth and migration through attenuation of NF-kB activity and apoptosis induction. Mol Cell Biochem, 379, 7-18. https://doi.org/10.1007/s11010-013-1621-y
  88. Tumbas VT, Canadanovic-Brunet JM, Cetojevic-Simin DD, et al (2012). Effect of rosehip (Rosa canina L.) phytochemicals on stable free radicals and human cancer cells. J Sci Food Agric, 92, 1273-81. https://doi.org/10.1002/jsfa.4695
  89. Vidya Priyadarsini R, Senthil Murugan R, Maitreyi S, et al (2010). The flavonoid quercetin induces cell cycle arrest and mitochondria-mediated apoptosis in human cervical cancer (HeLa) cells through p53 induction and NF-kB inhibition. Eur J Pharmacol, 649, 84-91. https://doi.org/10.1016/j.ejphar.2010.09.020
  90. Virgili F, Acconcia F, Ambra R, et al (2004). Nutritional flavonoids modulate estrogen receptor alpha signaling. IUBMB Life, 569, 145-51.
  91. Wang SY, Yang KW, Hsu YT, Chang CL, Yang YC (2001). The differential inhibitory effects of genistein on the growth of cervical cancer cells in vitro. Neoplasma, 48, 227-33.
  92. Wu C, Chen F, Rushing JW, et al (2006). Antiproliferative activities of parthenolide and golden feverfew extract against three human cancer cell lines. J Med Food, 9, 55-61. https://doi.org/10.1089/jmf.2006.9.55
  93. Xie F, Lang Q, Zhou M, et al (2012). The dietary flavonoid luteolin inhibits Aurora B kinase activity and blocks proliferation of cancer cells. Eur J Pharm Sci, 46, 388-96. https://doi.org/10.1016/j.ejps.2012.03.002
  94. Xie SR, Wang Y, Liu CW, Luo K, Cai YQ (2012). Liquiritigenin inhibits serum-induced HIF-1${\alpha}$ and VEGF expression via the AKT/mTOR-p70S6K signalling pathway in HeLa cells. Phytother Res, 26, 1133-41. https://doi.org/10.1002/ptr.3696
  95. Xu Q, Xie H, Wu P, Wei X (2013). Flavonoids from the capitula of Eriocaulon australe. Food Chem, 139, 149-54. https://doi.org/10.1016/j.foodchem.2013.01.018
  96. Yang L, Zheng XL, Sun H, et al (2011). Catalase suppressionmediated H(2)O(2) accumulation in cancer cells by wogonin effectively blocks tumor necrosis factor-induced NF-kB activation and sensitizes apoptosis. Cancer Sci, 102, 870-6. https://doi.org/10.1111/j.1349-7006.2011.01874.x
  97. Xu W, Liu J, Li C, Wu HZ, Liu YW (2008). Kaempferol-7-Obeta-D-glucoside (KG) isolated from Smilax china L. rhizome induces G2/M phase arrest and apoptosis on HeLa cells in a p53-independent manner. Cancer Lett, 264, 229-40. https://doi.org/10.1016/j.canlet.2008.01.044
  98. Xu Y, Xin Y, Diao Y, et al (2011). Synergistic effects of apigenin and paclitaxel on apoptosis of cancer cells. PLoS One, 6, 29169. https://doi.org/10.1371/journal.pone.0029169
  99. Yang L, Zhang HW, Hu R, et al (2009). Wogonin induces G1 phase arrest through inhibiting Cdk4 and cyclin D1 concomitant with and elevation in p21Cip1 in human cervical carcinoma HeLa cells. Biochem Cell Biol, 87, 933-41. https://doi.org/10.1139/O09-060
  100. Yang LL, Chang CC, Chen LG, Wang CC (2003). Antitumor principle constituents of Myrica rubra Var. acuminata. J Agric Food Chem, 51, 2974-9. https://doi.org/10.1021/jf026188i
  101. Yashar CM, Spanos WJ, Taylor DD, Gercel-Taylor C (2005). Potentiation of the radiation effect with genistein in cervical cancer cells. Gynecol Oncol, 99, 199-205. https://doi.org/10.1016/j.ygyno.2005.07.002
  102. Ying TH, Yang SF, Tsai SJ, et al (2012). Fisetin induces apoptosis in human cervical cancer HeLa cells through ERK1/2-mediated activation of caspase-8-/caspase-3-dependent pathway. Arch Toxicol, 86, 263-73. https://doi.org/10.1007/s00204-011-0754-6
  103. Yokoyama M, Noguchi M, Nakao Y, et al (2008). Antiproliferative effects of the major tea polyphenol, (-)-epigallocatechin gallate and retinoic acid in cervical adenocarcinoma. Gynecol Oncol, 108, 326-31. https://doi.org/10.1016/j.ygyno.2007.10.013
  104. Yokoyama M, Noguchi M, Nakao Y, Pater A, Iwasaka T (2004). The tea polyphenol, (-)-epigallocatechin gallate effects on growth, apoptosis, and telomerase activity in cervical cell lines. Gynecol Oncol, 92, 197-204. https://doi.org/10.1016/j.ygyno.2003.09.023
  105. Zeng F, Tian L, Liu F, et al (2012a). Induction of apoptosis by casticin in cervical cancer cells: reactive oxygen speciesdependent sustained activation of Jun N-terminal kinase. Acta Biochem Biophys Sin (Shanghai), 44, 442-9. https://doi.org/10.1093/abbs/gms013
  106. Yuan CH, Fillippova M, Tungteakkhun SS, Duerksen-Hughes PJ, Krstenansky JL (2012). Small molecule inhibitors of the HPV16-E6 interaction with caspase 8. Bioorg Med Chem Lett, 22, 2125-9. https://doi.org/10.1016/j.bmcl.2011.12.145
  107. Yuan X, Zhang B, Chen N, et al (2012). Isoliquiritigenin treatment induces apoptosis by increasing intracellular ROS levels in HeLa cells. J Asian Nat Prod Res, 14, 789-98. https://doi.org/10.1080/10286020.2012.694873
  108. Yuan X, Zhang B, Gan L, et al (2013). Involvement of the mitochondrion-dependent and the endoplasmic reticulum stress-signaling pathways in isoliquiritigenin-induced apoptosis of HeLa cell. Biomed Envrion Sci, 26, 268-76.
  109. Zeng XT, Xiong PA, Wang F, et al (2012b). Passive smoking and cervical cancer risk: a meta-analysis based on 3230 cases and 2982 controls. Asian Pac J Cancer Prev, 13, 3687-93. https://doi.org/10.7314/APJCP.2012.13.8.3687
  110. Zhang B, Liu JY, Pam JS, et al (2006). Combined treatment of ionizing radiation with genistein on cervical cancer HeLa cells. J Pharmacol Sci, 102, 129-35. https://doi.org/10.1254/jphs.FP0060165
  111. Zhang Q, Tang X, Lu Q, et al (2006). Green tea extract and (-)-epigallocatechin-3-gallate inhibit hypoxia- and seruminduced HIF-1alpha protein accumulation and VEGF expression in human cervical carcinoma and hepatoma cells. Mol Cancer Ther, 5, 1227-38. https://doi.org/10.1158/1535-7163.MCT-05-0490
  112. Zhang T, Chen X, Qu L, et al (2004). Chrysin and its phosphate ester inhibit cell proliferation and induce apoptosis in Hela cells. Bioorg Med Chem, 12, 6097-105. https://doi.org/10.1016/j.bmc.2004.09.013
  113. Zhang T, Du J, Liu L, et al (2012). Inhibitory effects and underlying mechanism of 7-hyrdoxyflavone phosphate ester in HeLa cells. PLoS One, 7, 36652. https://doi.org/10.1371/journal.pone.0036652
  114. Zhang Y, Ge Y, Chen Y, et al (2012). Cellular and molecular mechanisms of silibinin induces cell-cycle arrest and apoptosis on HeLa cells. Cell Biochem Funct, 30, 243-8. https://doi.org/10.1002/cbf.1842
  115. Zheng PW, Chiang LC, Lin CC (2005). Apigenin induced apoptosis through p53-dependent pathway in human cervical carcinoma cells. Life Sci, 76, 1367-79. https://doi.org/10.1016/j.lfs.2004.08.023
  116. Zhou N, Yan Y, Li W, et al (2009). Genistein inhibition of topoisomerase IIalpha expression participated by Sp1 and Sp3 in HeLa cell. Int J Mol Sci, 10, 3255-68. https://doi.org/10.3390/ijms10073255
  117. Zhu X, Wang J, Ou Y, Han W, Li H (2013). Polyphenol extract of Phyllanthus emblica (PEEP) induces inhibition of cell proliferation and triggers apoptosis in cervical cancer cells. Eur J Med Res, 18, 46. https://doi.org/10.1186/2047-783X-18-46
  118. Zou C, Liu H, Feugang JM, et al (2010). Green tea compound in chemoprevention of cervical cancer. Int J Gynecol Cancer, 20, 617-24. https://doi.org/10.1111/IGC.0b013e3181c7ca5c

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