title: Cytotoxic effect of evodiamine in SGC-7901 human gastric adenocarcinoma             cells via simultaneous induction of apoptosis and autophagy.
abstract: Evodiamine, an alkaloid isolated from Evodia rutaecarpa, possesses potent             anticancer activity. Although many reports have elucidated the cytotoxic effects             of evodiamine in a variety of cancer cells, little is known about the mechanism             of evodiamine-induced cytotoxic activity in gastric cancer cells. To date, no             report has addressed the synchronized role of autophagy and apoptosis in evodiamine-induced             cytotoxic activity. This study was conducted to investigate the synchronized role             of autophagy and apoptosis in evodiamine-induced cytotoxic activity on SGC-7901             human gastric adenocarcinoma cells and further to elucidate the underlying molecular             mechanisms. The MTT assay was used to examine the cytotoxicity of evodiamine against             SGC-7901 gastric adenocarcinoma cells. The effects of evodiamine on the cell cycle             and apoptosis were measured by flow cyto-metry and cellular morphology was observed             under a phase contrast microscope. Acridine orange (AO) staining was used to detect             autophagy. The expression levels of Bcl-2 and Bax were detected by Western blotting.             The expression level of Beclin‑1 in SGC-7901 cells was monitored by reverse transcription-polymerase             chain reaction (RT-PCR). Here, we found that evodiamine significantly inhibited             the proliferation of SGC-7901 cells and induced G2/M phase cell cycle arrest.             Furthermore, both autophagy and apoptosis were activated during the evodiamine-induced             death of SGC-7901 cells. Evodiamine-induced autophagy is partially involved in             the death of SGC-7901 cells which was confirmed by using the autophagy inhibitor             3-methyladenine (3-MA). Additionally, Beclin-1 is involved in evodiamine-induced             autophagy and the pro-apoptotic mechanisms of evodiamine may be associated with             down-regulation of Bcl-2 and up-regulation of Bax expression. The inhibitory effects             on SGC-7901 cells were associated with apoptosis, autophagy and cell cycle arrest             at the G2/M phase in a dose-dependent manner. These results suggest that evodiamine             is an effective natural compound for the treatment of gastric cancer and may represent             a candidate for in vivo studies of monotherapies or combined antitumor therapies.
authors.affiliation: Central Research Laboratory, Jilin University Bethune Second Hospital, Changchun 130041, PR China.
authors.forename: Azhar
authors.initials: A
authors.lastname: Rasul
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
authors.forename: Lili
authors.initials: L
authors.lastname: Zhong
authors.forename: Muhammad
authors.initials: M
authors.lastname: Khan
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.forename: Tonghui
authors.initials: T
authors.lastname: Ma
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001343:Autophagy / Q000187:drug effects* / Q000235:genetics; D000071186:Beclin-1; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D010936:Plant Extracts / Q000633:toxicity*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011799:Quinazolines / Q000633:toxicity*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D011799:Quinazolines; D051028:bcl-2-Associated X Protein; C049639:evodiamine