Introduction: Cervical cancer is one of the most common cancers in women worldwide and its incidence is associated with persistent infection with a high-risk genotype of human papillomavirus (HPV). The HPV oncoproteins, E6 and E7 are thought to direct uncontrolled growth of cervical cancer cells through decreased levels of p53 and inhibition of retinoblastoma protein (pRb), respectively. The use of chemopreventive agents, such as curcumin, in healthy women at high risk for developing cervical cancer (women with a pre-malignant lesion or infection with high risk HPV) may be a non-invasive and cost effective method for the treatment of cervical intraepithelial neoplasia. Specifically, the prevention of oncogenic viral protein expression (primarily HPV E6 and E7) is highly desirable. In this study, we have investigated the effect of curcumin on the growth of cervical cancer cells and the expression of HPV oncoproteins E6/E7. Methods: We have assessed the effect of curcumin (diferuloyl methane) on a variety of cervical cancer cell lines, including Caski, SiHa, C33A, C4-I and HeLa cells, using the CellTiter96 Aqueous One Solution Cell Proliferation Assay (Promega). Additionally, we have also established and utilized raft culture methods to investigate the inhibitory effect of curcumin in a more physiologically relevant in vitro model. To determine the effects of curcumin on the cellular and molecular level, immunoblotting, flow cytometry, immunofluorescence, and real time PCR analyses were performed using the Caski cell line model. Results: Curcumin shows a time and dose dependent inhibition on proliferation and colony forming ability in all cervical cancer cell lines examined. Additionally, curcumin treatment inhibits cellular migration in scratch assays. In Caski cells, curcumin treatment induces apoptosis by cleavage of both Poly (ADP-ribose) polymerase (PARP) and caspase 3. Interestingly, our results also suggest that curcumin causes suppression of HPV16 oncoproteins E6/E7. In a raft culture model using Caski cells, curcumin treatment reduced cell growth and thickening of the growing raft. Conclusion: We have shown that curcumin inhibits the growth of cervical cancer cells in both monolayer and raft culture models. Importantly, curcumin treatment also modulates the expression of HPV16 E6/E7 oncoproteins. Results of this study suggest a chemopreventive and therapeutic role of curcumin for cervical cancer.
Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 963.
100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO