β‐elemene inhibited expression of DNA methyltransferase 1 through activation of ERK 1/2 and AMPK α signalling pathways in human lung cancer cells: the role of Sp1

β‐elemene, a compound derived from R hizoma zedoariae , is a promising new plant‐derived drug with broad‐spectrum anticancer activity. However, the underlying mechanism by which this agent inhibits human lung cancer cell growth has not been well elucidated. In this study, we showed that β‐elemene inhibits human non‐small cell lung carcinoma ( NSCLC ) cell growth, and increased phosphorylation of ERK 1/2, Akt and AMPK α. Moreover, β‐elemene inhibited expression of DNA methyltransferase 1 ( DNMT 1), which was not observed in the presence of the specific inhibitors of ERK ( PD 98059) or AMPK (compound C). Overexpression of DNMT 1 reversed the effect of β‐elemene on cell growth. Interestingly, metformin not only reversed the effect of β‐elemene on phosphorylation of Akt but also strengthened the β‐elemene‐reduced DNMT 1. In addition, β‐elemene suppressed Sp1 protein expression, which was eliminated by either ERK 1/2 or AMPK inhibitor. Conversely, overexpression of Sp1 antagonized the effect of β‐elemene on DNMT 1 protein expression and cell growth. Taken together, our results show that β‐elemene inhibits NSCLC cell growth via ERK 1/2‐ and AMPK α‐mediated inhibition of transcription factor Sp1, followed by reduction in DNMT 1 protein expression. Metformin augments the effect of β‐elemene by blockade of Akt signalling and additively inhibition of DNMT 1 protein expression. The reciprocal ERK 1/2 and AMPK α signalling pathways contribute to the overall responses of β‐elemene. This study reveals a potential novel mechanism by which β‐elemene inhibits growth of NSCLC cells.