title: Apoptosis of human non-small-cell lung cancer A549 cells triggered by evodiamine through MTDH-dependent signaling pathway.
abstract: Metadherin (MTDH), a novel oncoprotein, has been implicated in the carcinogenesis in various aspects of tumor malignancy. Overexpression of the MTDH promotes the survival and proliferation of lung cancer cells. Agent that can suppress MTDH activation would have potential to be developed for cancer therapeutics. In this study, we investigated the antitumor effect of evodiamine in human non-small-cell lung carcinoma (NSCLC) A549 cell line and the inhibitory effect of evodiamine on MTDH pathway. 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and annexin V/propidium iodide (PI) staining assays demonstrated that evodiamine or MTDH short hairpin RNA (shRNA) significantly inhibited proliferation of A549 cells via induction of apoptosis. Besides, evodiamine or MTDH shRNA-induced activation of the caspase-3 in A549 cells under same conditions. In addition, Western blotting analysis showed that treatment of A549 cells with evodiamine or MTDH shRNA resulted in an increase of proapoptotic protein Bax expression but decreased the expression levels of antiapoptotic protein Bcl-2 and MTDH, which altogether account for apoptotic cell death. Taken together, our results suggest that the evodiamine suppress the proliferation of lung cancer cells, at least, in part, via inhibition of MTDH expression and activation of apoptosis.
authors: Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors: Yanmei
authors: Y
authors: Zou
authors: Xiaomin
authors: X
authors: Qin
authors: Hua
authors: H
authors: Xiong
authors: Feng
authors: F
authors: Zhu
authors: Tao
authors: T
authors: Chen
authors: Hongge
authors: H
authors: Wu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D053148:Caspase 3 / Q000096:biosynthesis; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D011799:Quinazolines / Q000008:administration & dosage*; D034741:RNA, Small Interfering / Q000008:administration & dosage; D016601:RNA-Binding Proteins; D015398:Signal Transduction; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: D015815:Cell Adhesion Molecules; C483039:MTDH protein, human; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011799:Quinazolines; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D051028:bcl-2-Associated X Protein; C049639:evodiamine; D053148:Caspase 3
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