Growth Inhibitory Effect of Wedelolactone in Combination with Cisplatin on PA-1 Ovarian Cancer Cell Line

Abstract

Drug resistance and poor therapeutic outcomes are the emerging problems pertaining to cisplatin treatment in ovarian cancer. The effectiveness of the conventional chemotherapeutic medication could be improved by combining with natural drugs. In the current study, Wedelolactone (WDL) a natural coumestan, in combination with Cisplatin (Cis) was determined to be a potent anti-cancer drug as evidenced by their capacity to bring about cytotoxicity by decreasing NF-κB expression in PA-1 ovarian cancer cells. “Cell viability assays” were carried out and the effective combination of wedelolactone with Cisplatin were confirmed by PCR and western blot analysis. The determined IC50 (10µM) of WDL displayed advantageous anti-cancer effect in PA-1 cells compared to Cis treatment. Furthermore, the combination of wedelolactone (5µM) and cisplatin(3µM) also down regulated NF-κB expression which is a key player of various cancer promoting events such as drug resistance, apoptotic inhibition, inflammation and angiogenesis. WDL potentiates the sensitivity of PA-1 cells towards cisplatin by decreasing the ETS1 and P-gp expression which are involved in MDR mechanism. Overall, this study suggest that Wedelolactone can be used to sensitize ovarian tumors to standard cancer chemotherapeutics.