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Evodiamine, an alkaloid isolated from Evodia rutaecarpa, possesses potentanticancer activity. Although many reports have elucidated the cytotoxic effectsof evodiamine in a variety of cancer cells, little is known about the mechanismof evodiamine-induced cytotoxic activity in gastric cancer cells. To date, noreport has addressed the synchronized role of autophagy and apoptosis in evodiamine-inducedcytotoxic activity. This study was conducted to investigate the synchronized roleof autophagy and apoptosis in evodiamine-induced cytotoxic activity on SGC-7901human gastric adenocarcinoma cells and further to elucidate the underlying molecularmechanisms. The MTT assay was used to examine the cytotoxicity of evodiamine againstSGC-7901 gastric adenocarcinoma cells. The effects of evodiamine on the cell cycleand apoptosis were measured by flow cyto-metry and cellular morphology was observedunder a phase contrast microscope. Acridine orange (AO) staining was used to detectautophagy. 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-polymerasechain reaction (RT-PCR). Here, we found that evodiamine significantly inhibitedthe proliferation of SGC-7901 cells and induced G2/M phase cell cycle arrest.Furthermore, both autophagy and apoptosis were activated during the evodiamine-induceddeath of SGC-7901 cells. Evodiamine-induced autophagy is partially involved inthe death of SGC-7901 cells which was confirmed by using the autophagy inhibitor3-methyladenine (3-MA). Additionally, Beclin-1 is involved in evodiamine-inducedautophagy and the pro-apoptotic mechanisms of evodiamine may be associated withdown-regulation of Bcl-2 and up-regulation of Bax expression. The inhibitory effectson SGC-7901 cells were associated with apoptosis, autophagy and cell cycle arrestat the G2/M phase in a dose-dependent manner. These results suggest that evodiamineis an effective natural compound for the treatment of gastric cancer and may representa candidate for in vivo studies of monotherapies or combined antitumor therapies.

Cytotoxic effect of evodiamine in SGC-7901 human gastric adenocarcinoma cells via simultaneous induction of apoptosis and autophagy