Abstract A71: Molecular trail for the action of a metal-based drug in HPV positive cervical cancer cells

Abstract

Abstract A71 Cervical cancer is one of the most prevalent female cancers in world. The treatment for cervical cancer includes chemotherapy. Most potential standard chemotherapeutic agents have side effects. A need-based approach for developing new anti cancer agents from metal compounds with fewer side effects will have enormous implications. Opportunities exist to exploit metal-based drugs in the discovery and development of pharmaceuticals against cancers. Vanadium is a transition metal widely distributed in the environment, which is also a dietary micronutrient. The antidiabetic and anticancer activities of the oxovanadium complexes are recently known. In this study, human cervical cancer cell line SiHa, which is HPV16 - positive has been employed to determine the anticarcinogenic property of two oxovanadium complexes, OVK 49 and OVK 89. Among these OVK 49 proved to be more effective than OVK 89. Both complexes inhibited the growth of SiHa cells in a concentration and time dependent manner. Treatment of cells with oxovanadium complexes caused loss of mitochondrial membrane potential (ΔΨm) and morphological changes characteristic of apoptosis, such as the nuclear condensation. Moreover oxovanadium complex induced apoptosis, which involved release of mitochondrial cytochrome c and activation of caspase 8 and 9. The molecular mechanism behind the apoptotic induction due to these oxovanadium complexes is well established in this study. The E6 oncoprotein of human papillomaviruses has the potential to funtionally antagonize p53. Here it has also been investigated whether this reflects the regulation of p53 expression in HPV positive cervical cells. It has also been found that p21 was efficiently induced and HPV E6, E7 p53 and GADD45 were decreased by OVK 49 and 89 in SiHa cells. These results suggests that inspite of the presence of E6 protein HPV 16 positive cervical cancer cell lines are capable of responding efficiently to DNA damage provoked by metal based drug treatment through a p53 dependent pathway. Citation Information: Cancer Prev Res 2008;1(7 Suppl):A71.