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

Li,Guangcai; He,Yuan; Yao,Jun; Huang,Chuying; Song,Xiusheng; Deng,Yan; Xie,Sheng; Ren,Jie; Jin,Meng; Liu,Huiguo

doi:10.3892/or.2016.5166

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

Authors:
- Guangcai Li
- Yuan He
- Jun Yao
- Chuying Huang
- Xiusheng Song
- Yan Deng
- Sheng Xie
- Jie Ren
- Meng Jin
- Huiguo Liu
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Affiliations: Department of Respiratory Diseases, Tongji Hospital, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, P.R. China, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei 445000, P.R. China
Published online on: October 12, 2016 https://doi.org/10.3892/or.2016.5166
Pages: 3504-3512

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Abstract

Angelicin is a member of a well-known class of chemical photosensitizes that have anticancer properties 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.

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