Marine Natural Products with Cytotoxic Properties against Epithelial Ovarian Cancer

Abstract

Epithelial ovarian cancer (EOC) is a common gynecological cancer and a leading cause of death, especially because the tumors develop resistance to cisplatin. New compounds are needed to achieve better disease control and survival. We examined the cytotoxic effect of Gallic acid (GA), Hymenialdisine, and Malformin A1 (MA1) on human ovarian cancer cells. Cytotoxicity was tested using cisplatin-sensitive (A2780s) and cisplatin-resistant (A2780cp) ovarian cancer cell lines, and a normal ovarian tissue cell line (HOSE6-3) using AlamarBlue assay, Hoechst dye, and flow cytometry, and the genes and proteins of interest were assessed using western blot, and qRT-PCR. The IC50 of Hymenialdisine was 146.8 μM for A2780s cells and >300 μM for A2780cp cell lines. Both GA and MA1 decreased cell viability in a concentration-dependent manner. The IC50 of GA was 103 μM for A2780s cells, 189 μM for A2780cp cells and 262 μM for HOSE6-3 cell lines, for MA1 IC50 was 0.23 μM for A2780s and 0.34 μM for A2780cp. This was in comparison to IC50 of 31.4 μM and 76.9 μM, for A2780s cells, and A2780cp cells respectively for cisplatin. The combination of GA and MA1 with cisplatin revealed synergistic action, especially in A2780cp cell lines. The results suggest that both GA and MA1 may help overcome the resistance to cisplatin through the synergistic effect. Hence, the cytotoxic potential of GA and MA1 merit further investigation.