We showed for the first time that β-elemene inhibits growth of NSCLC cells via both extracellular signal-regulated kinase 1/2 (ERK1/2)- and AMP-activated protein kinase alpha (AMPKα)-mediated inhibition of transcription factor Sp1, followed by reduction in DNMT1 expression. Here, MAPK3 is linked to non-small cell lung carcinoma.