No 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 in vitro. Angelicin also inhibited the migration of non-small cell lung cancer (NSCLC) A549 cells in a Transwell assay in a dose-dependent manner. In addition, after angelicin treatment, the expression levels of Bax, cleaved caspase-3 and cleaved caspase-9 were increased, and Bcl-2 expression was decreased. Moreover, our results indicate that angelicin inhibits NSCLC growth not only by downregulating cyclin B1, cyclin E1 and Cdc2, which are related to the cell cycle, but also by reducing MMP2 and MMP9 and increasing E-cadherin expression levels. Furthermore, extracellular signal-regulated kinase (ERK)1/2 and c-Jun NH2-terminal protein kinase (JNK)1/2 phosphorylation increased in parallel with the angelicin treatments. The inhibition of ERK1/2 and JNK1/2 by specific inhibitors significantly abrogated angelicin-induced cell apoptosis, cell cycle arrest and migration inhibition. We established in vivo A549 cell transplant and metastasis models and found that angelicin exerted a significant inhibitory effect on A549 cell growth and lung metastasis. Overall, our results suggested that angelicin is able to inhibit NSCLC A549 cell growth and metastasis by targeting ERK and JNK signaling, which demonstrates potential for NSCLC therapy.

It has been suggested that β2‐adrenergic receptor (β2‐AR)‐mediated signaling induced by catecholamines regulates the degradation of p53. However, the underlying molecular mechanisms were not known. In the present study, we demonstrated that catecholamines upregulated the expression of silent information regulator 1 (Sirt1) through activating β2‐AR‐mediated signaling pathway, since selective β2‐AR antagonist ICI 118, 551 and non‐selective β‐blocker proprenolol effectively repressed isoproterenol (ISO)‐induced Sirt1 expression. Catecholamines inhibited doxorubicin (DOX)‐induced p53 acetylation and transcription‐activation activities by inducing the expression of Sirt1. Knockdown of the Sirt1 expression by the specific siRNA remarkably blocked the inhibitory effects of ISO on DOX‐induced p53 acetylation. In addition, we demonstrated that catecholamines induced resistance of cervical cancer cells to chemotherapeutics both in vitro and in vivo and that β2‐AR was overexpressed in cervical cancer tissues. Our data suggest that the p53‐dependent, chemotherapeutics‐induced cytotoxicity in cervical cancer cells may be compromised by catecholamines‐induced upregulation of the Sirt1 expression through activating the β2‐AR signaling.

No abstract