In this study, we demonstrate for the first time that the semisynthetic derivative of cucurbitacin B (DACE) is a potent suppressor of human NSCLC cell growth in vitro through its effects on the actin-cytoskeleton, EGF receptor and its downstream effectors PI3Kinase, ERK1/2 and STAT3, and apoptotic proteins. This evidence concerns the gene MAPK3 and non-small cell lung carcinoma.