Angelicin inhibits human lung carcinoma A549 cell growth and migration through regulating JNK and ERK pathways.

Abstract

Angelicin is a member of a well-known class of chemical photosensitizes that have anticancer proper-ties in several cancer cell lines. However, the effects and the potential underlying mechanisms of angelicin action on human lung cancer cells remain unclear. Here, we report that angelicin has an essential role in inhibiting human lung carcinoma growth and metastasis. We found that angelicin markedly induced cell apoptosis and arrested the cell cycle invitro. Angelicin also inhibited the migration of non-small cell lung cancer(NSCLC) A549cells in a Transwell assay in a dose-dependent manner. Inaddition, after angelicin treatment, the expression levels of Bax, cleaved caspase-3and cleaved caspase-9 were increased, andBcl-2 expression was decreased. Moreover, our results indicate that angelicin inhibits NSCLC growth not only by downregulating cyclinB1, cyclinE1 andCdc2, which are related to the cell cycle, but also by reducing MMP2 andMMP9 and increasing E-cadherin expression levels. Furthermore, extracellular signal-regulated kinase(ERK)1/2 andc-Jun NH2-terminal protein kinase(JNK)1/2 phosphorylation increased in parallel with the angelicin treatments. The inhibition of ERK1/2 andJNK1/2 by specific inhibitors significantly abrogated angelicin-induced cell apoptosis, cell cycle arrest and migration inhibition. We established invivoA549cell transplant and metastasis models and found that angelicin exerted a significant inhibitory effect on A549cell growth and lung metastasis. Overall, our results suggested that angelicin is able to inhibit NSCLCA549cell growth and metastasis by targeting ERK andJNK signaling, which demonstrates potential for NSCLC therapy.