Our data suggests that the inactivation of the proliferation (ERK) and pro-survival (AKT) pathways along with caspase-3 activation, PARP cleavage, and consequently DNA damage account, at least partly, for the anti-cancer effect of Frondoside A. Moreover, combination therapy either with oxaliplatin or 5-FU enhanced these effects and further clarified the capacity of Frondoside A to enhance the apoptosis induced mainly by 5-FU. The gene discussed is MAPK1; the disease is cancer.