title: 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 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.
authors.affiliation: 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.
authors.forename: Guangcai
authors.initials: G
authors.lastname: Li
authors.affiliation: The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei 445000, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: He
authors.affiliation: The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei 445000, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yao
authors.affiliation: 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.
authors.forename: Chuying
authors.initials: C
authors.lastname: Huang
authors.affiliation: The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei 445000, P.R. China.
authors.forename: Xiusheng
authors.initials: X
authors.lastname: Song
authors.affiliation: The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei 445000, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Deng
authors.affiliation: 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.
authors.forename: Sheng
authors.initials: S
authors.lastname: Xie
authors.affiliation: 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.
authors.forename: Jie
authors.initials: J
authors.lastname: Ren
authors.affiliation: 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.
authors.forename: Meng
authors.initials: M
authors.lastname: Jin
authors.affiliation: 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.
authors.forename: Huiguo
authors.initials: H
authors.lastname: Liu
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D011564:Furocoumarins / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D020935:MAP Kinase Signaling System; D008297:Male; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D011564:Furocoumarins; C011659:angelicin; D048049:Extracellular Signal-Regulated MAP Kinases