title: Evodiamine induces G2/M arrest and apoptosis via mitochondrial and endoplasmic reticulum pathways in H446 and H1688 human small-cell lung cancer cells.
abstract: The goal of this study was to evaluate the ability of EVO to decrease cell viability and promote cell cycle arrest and apoptosis in small cell lung cancer (SCLC) cells. Lung cancer has the highest incidence and mortality rates among all cancers. Chemotherapy is the primary treatment for SCLC; however, the drugs that are currently used for SCLC are less effective than those used for non-small cell lung cancer (NSCLC). Therefore, it is necessary to develop new drugs to treat SCLC. In this study, the effects of evodiamine (EVO) on cell growth, cell cycle arrest and apoptosis were investigated in the human SCLC cell lines NCI-H446 and NCI-H1688. The results represent the first report that EVO can significantly inhibit the viability of both H446 and H1688 cells in dose- and time-dependent manners. EVO induced cell cycle arrest at G2/M phase, induced apoptosis by up-regulating the expression of caspase-12 and cytochrome C protein, and induced the expression of Bax mRNA and by down-regulating of the expression of Bcl-2 mRNA in both H446 and H1688 cells. However, there was no effect on the protein expression of caspase-8. Taken together, the inhibitory effects of EVO on the growth of H446 and H1688 cells might be attributable to G2/M arrest and subsequent apoptosis, through mitochondria-dependent and endoplasmic reticulum stress-induced pathways (intrinsic caspase-dependent pathways) but not through the death receptor-induced pathway (extrinsic caspase-dependent pathway). Our findings suggest that EVO is a promising novel and potent antitumor drug candidate for SCLC. Furthermore, the cell cycle, the mitochondria and the ER stress pathways are rational targets for the future development of an EVO delivery system to treat SCLC.
authors.affiliation: Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Chunshu
authors.initials: C
authors.lastname: Fang
authors.affiliation: Medicine Engineering Research Center, Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Jingqing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Di
authors.initials: D
authors.lastname: Qi
authors.affiliation: Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Fan
authors.affiliation: Medicine Engineering Research Center, Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Jianchun
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Qunyou
authors.initials: Q
authors.lastname: Tan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects; D011799:Quinazolines / Q000494:pharmacology* / Q000627:therapeutic use; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; C049639:evodiamine