P0125 Effect of the combination of frondoside a with oxaliplatin or fluorouracil in the treatment of colon cancer

Abstract

Background Colorectal cancer is the third leading cause of cancer deaths in the world despite many therapeutic options. We have demonstrated that frondoside A, a triterpenoid glycoside isolated from an Atlantic sea cucumber, has potent in vitro and in vivo anticancer effects against human pancreatic, breast, and lung cancer. We also demonstrated that frondoside A was able to potentiate and/or to synergise the anti-cancer effects of gemcitabine, paclitaxel, and cisplatin in the treatment of pancreatic, breast, and lung cancer, respectively. These results suggest that frondoside A may have an anticancer potential in the treatment of colon cancer either alone, and/or in combination, with the standard cytotoxic drugs oxaliplatin and fluorouracil. Methods The impact of the treatments on cellular proliferation and apoptosis was determined using cell counter, FACS analysis, and caspase activities. Findings Frondoside A, oxaliplatin, and fluorouracil induced a concentration-dependent and time-dependent inhibition of cellular proliferation and induced apoptosis in a caspase-dependent manner in the three colorectal cancer cells HT29, HCT116, and HCT8/S11. Combinations of low concentrations of these drugs for 48 h in vitro indicate that frondoside A enhances the inhibition of cell proliferation and the induction of apoptosis mediated by oxaliplatin as well as by fluorouracil. Interpretation We believe that frondoside A will improve colon cancer therapy in combination with the standard cytotoxic drugs oxaliplatin and fluorouracil.