Regulation of cell growth through cell cycle arrest and apoptosis in HPV 16 positive human cervical cancer cells by tea polyphenols
- 360 Downloads
Cervical cancer is the second most common malignant neoplasm in women, in terms of both incidence and mortality rates worldwide. The polyphenolic constituents of tea (Camellia sinensis) have gained considerable attention because of its anti-cancer properties against a variety of cancers. Here we studied the effects of green and black tea polyphenols (GTP and BTP), on cellular proliferation and cell death in the SiHa cells (human cervical cancer) expressing the human papilloma virus (HPV)-16. The result showed that both GTP and BTP inhibited proliferation of cells in dose and time dependent manner. Cell cycle analysis showed anti-proliferative effect of GTP which is associated with an increase in the G2/M phase and apoptotic effect of BTP in 24 h treated SiHa cells. Further, on increase of incubation time for 48 h, GTP caused induction of apoptosis up to 20% of SiHa cells. The role GTP and BTP in apoptosis was further confirmed by reduction in mitochondrial membrane potential and increased levels of membrane phosphatidylserine. Thus, our data suggests that tea polyphenols exhibit anti-cancer potential against cervical cancer by inhibition of cell growth and induction of apoptosis.
KeywordsCervical cancer SiHa cells Tea polyphenols Anti-cancer effects Apoptosis
Authors are thankful to Dr. Ashwani Kumar, Director Indian Institute of Toxicology Research, Lucknow for his keen interest in the study. Authors are also thankful to Indian Council of Medical Research (India) for providing fellowship to MS, SP and ST. Thanks are also due to Indfrag chemical company, Bangalore, India for providing tea polyphenols.
- 3.Hougardy BM, Maduro JH, van der Zee AG, Willemse PH, de Jong S, de Vries EG (2005) Clinical potential of inhibitors of survival pathways and activators of apoptotic pathways in treatment of cervical cancer: changing the apoptotic balance. Lancet Oncol 6:589–598. doi: 10.1016/S1470-2045(05)70281-3 CrossRefPubMedGoogle Scholar
- 5.Katiyar SK, Mukhtar H (1997) Tea antioxidants in cancer chemoprevention. J Cell Biochem Suppl 27:59–67. doi: 10.1002/(SICI)1097-4644(1997)27 + <59::AID-JCB11>3.0.CO;2-G CrossRefPubMedGoogle Scholar
- 13.Hirose M, Mizoguchi Y, Yaono M, Tanaka H, Yamaguchi T, Shirai T (1997) Effects of green tea catechins on the progression or late promotion stage of mammary gland carcinogenesis in female Sprague–Dawley rats pretreated with 7,12 dimethylbenz(a)anthracene. Cancer Lett 112:141–147. doi: 10.1016/S0304-3835(96)04560-0 CrossRefPubMedGoogle Scholar
- 14.Kalra N, Seth K, Prasad S, Singh M, Pant AB, Shukla Y (2007) Theaflavins induced apoptosis of LNCaP cells is mediated through induction of p53, down-regulation of NF-kappa B and mitogen-activated protein kinases pathways. Life Sci 80:2137–2146. doi: 10.1016/j.lfs.2007.04.009 CrossRefPubMedGoogle Scholar
- 29.Jo EH, Kim SH, Ra JC, Kim SR (2005) Chemopreventive properties of the ethanol extract of Chinese licorice (Glycyrrhiza uralensis) root: induction of apoptosis and G1 cell cycle arrest in MCF-7 human breast cancer cells. Cancer Lett 230:239–247. doi: 10.1016/j.canlet.2004.12.038 CrossRefPubMedGoogle Scholar
- 31.Eastman A (1999) The mechanism of action of cisplatin: from adducts to apoptosis. In: Lippert B (ed) Cisplatin. Chemistry and biochemistry of a leading anticancer drug. Wiley, Basel, Switzerland, pp 111–134Google Scholar
- 34.Bettuzzi S, Brausi M, Rizzi F, Castagnetti G, Peracchia G, Corti A (2006) Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: a preliminary report from a one-year proof-of-principle study. Cancer Res 66:1234–1240. doi: 10.1158/0008-5472.CAN-05-1145 CrossRefPubMedGoogle Scholar
- 35.Luo H, Tang L, Tang M et al (2006) Phase IIa chemoprevention trial of green tea polyphenols in high-risk individuals of liver cancer: modulation of urinary excretion of green tea polyphenols and 8-hydroxydeoxyguanosine. Carcinogenesis 27:262–268. doi: 10.1093/carcin/bgi147 CrossRefPubMedGoogle Scholar