Back ground: Cervical cancer is the most common cancer in Indian females and is associated with infection with high risk Human papillomaviruses (HPVs). Prolonged use of oral contraceptives has been established as a risk factor for cervical cancer which is mediated by elevated estradiol level. Curcumin (Diferuloyl methane), a chemopreventive agent induces apoptosis in cervical cancer cells. The present study investigated whether curcumin could protect against the proliferative effect of estradiol in cervical cancer cell lines SiHa, HeLa, CaSki and C33A. Methods: HPV positive cervical cancer cell lines SiHa, HeLa, CaSki and HPV negative C33A cells were cultured in DMEM/RPMI/MEM media respectively, supplemented with 10% FBS in a humidified atmosphere of 5% CO2 at 37ºC. They were treated with 10 and 30 nM estradiol for 24 hrs followed by 25 and 50\#956;M curcumin treatment for 24 hrs. Apoptosis was measured by flow cytometery. Telomerase activity was studied using PCR ELISA. The expression of various proteins like PCNA, p16 was assessed by ICC and confocal microscopy. Expression of viral oncoproteins E6 and E7, cyclin D1, p53 and p73 was assessed by western blotting. Results: Treatment of cervical cancer cells with estradiol resulted in two fold increase in proliferation after 24 hrs in HPV positive cell lines HeLa, SiHa and CaSki but not in HPV negative cell line C33A. Treatment with curcumin of these estradiol pretreated cell lines inhibited proliferation by inducing apoptosis in HPV positive cell lines. An increase in Telomerase activity, protein expression of viral oncoproteins E6 and E7, PCNA, p16 and cyclin D1 was seen in HPV positive cell lines on treatment with estradiol, but after treatment with curcumin the levels of E7, PCNA and Cyclin D1 were reduced, thereby demonstrating the antiproliferative effect of curcumin, by inducing apoptosis. However, the HPV negative cell line C33A remained unaffected on estradiol treatment, but showed increased apoptosis on treatment with curcumin. This was accompanied with a decrease in Telomerase activity, PCNA, p16 levels and an increase in p53 and p73 proteins. Conclusion: Curcumin appears to act as an antagonist to estradiol by inhibiting its proliferative effect in HPV positive cervical cancer cell lines.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2380.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO