Abstract
Ellagic Acid is a naturally occurring compound that demonstrated anti cancer activity in vitro and in vivo. Ellagic acid inhibits protein kinase CK2, which has been identified as a promoter of tumorogenesis. Blocking CK2 activity can reactivate dormant cellular defensive mechanism and further block signaling pathways that induce cancer. In this study, we are testing HPV 18 positive cervical cancer cells (HeLa) to investigate the effect of ellagic acid on CK2 kinase activity, HPV oncogenes E6 and E7 expression and downstream targets leading to cell death in vitro and in vivo. Treating HeLa cells with ellagic acid induced in vitro cell cycle arrest and caspase mediated apoptosis in both time and dose dependent manner. Ellagic acid inhibited CK2 phosphorylation activity, as well as the expression of viral oncogenes E6 and E7. Inhibition of HPV oncogene expression was accompanied by an increase in P53 and a decrease in cyclin A expression. Ellagic acid treatment induced cytochrome c release in the cytosol and subsequent activation of caspase 3, which led to the fragmentation of Poly (ADP) RibosePolymerase (PARP) at the end of the caspase cascade. Finally, mice treated with ellagic acid demonstrated inhibition of cervical cancer xenograft growth and longer survival compared to vehicle-treated mice confirming the potent anti-tumor activity of ellagic acid. Our results suggest that ellagic acid has anti-tumor and anti-viral properties which could make it suitable for the prevention of HPV induced cervical carcinoma.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1933. doi:1538-7445.AM2012-1933