Here, we demonstrate that the inhibition of AKT and ERK phosphorylation is crucial for the anti-tumor activity of Frondoside A. These results are in agreement with previous reports showing that Frondoside A inhibited AKT and ERK1/2 activation in TPA-stimulated breast cancer cells [18] and ERK1/2 activation in PGE2-stimulated breast cancer cells [19]. This evidence concerns the gene MAPK3 and neoplasm.