LAWSONE INHIBITS CELL GROWTH AND IMPROVES THE EFFICACY OF CISPLATIN IN SKOV-3 OVARIAN CANCER CELL LINES

Abstract

Background: Lawsone (LWS) is a colored napthoquinone moiety found in plant Lawsonia inermis L. (Lythraceae) it is used as precursor for synthesis some anticancer drugs. In present research we evaluate the effect of LWS alone and in combination with Cisplatin (CP) on SKOV-3 ovarian cancer cells. Materials and Methods: Cell proliferation studies were done by MTT assay while the cell apoptosis studies were carried by performing nuclear Hoechst 33258 staining. Cell cycle analysis was done by Flow cytometric studies, Immunoblotting studies for protein expression was done, proteins controlling cell cycle such as cyclinD1, cyclin E, cyclin A, cyclin B1 and Cip1/p21 and p53 which also are cyclin dependent inhibitors of protein kinase were estimated. Annexin V staining was done to mark extent of apoptosis, expression of apoptotic protein such as Bcl-2, Bax, Bax/Bcl-2 ratio and activity of caspase 3. Results: LWS alone and in combination with CP suppressed the growth of SKOV-3 cells in dose-dependent manner. Treatment inhibited SKOV-3 cells by arresting of G1/G0 phase in the cell cycle, by increasing the expression of p53 and Cip1/p21 followed by decreasing levels of two important proteins cyclin E and cyclin D1. LWS was found to induce apoptosis via decreasing the levels of Bcl-2, improving Bax:Bcl-2 ratio and activating caspase 3. Conclusion: Results of this study clearly indicate LWS alone and in combination with CP have antiproliferative effect, causes apoptosis of SKOV-3 cells via suppressing Bcl-2. LWS could be a useful compound for treatment of ovarian cancer.