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

Abstract

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 evodiamineinduced 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 cytometry 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.

Evodiamine inhibits PDGF-BB-induced proliferation of rat vascular smooth muscle cells through the suppression of cell cycle progression and oxidative stress

“…Therefore, the observation that PDGF-BB increased and evodiamine decreased the expression of p21 in the present study was not unusual. Of note, the inhibitory effects of evodiamine on cell cycle progression have been previously observed in various human tumor cell lines, including small-cell lung cancer cells (20), gastric cancer cells (11), breast cancer cells (21), gastric adenocarcinoma cells (22) and cervical carcinoma HeLa cells (23), and are considered to be important in the antitumor action of evodiamine. The data obtained in the present study extends the current recognition of evodiamine, and suggested that the regulation of cell cycle progression by evodiamine may be general and function in a broader range of cell types, including tumor cells and vascular cells.…”

Anti-Proliferative Effects of Evodiamine in Human Lung Cancer Cells

“… 20 , 21 In previous reports, evodiamine induced autophagy and apoptosis in U87-MG glioblastoma and SGC-7901 gastric cancer cells. 22 , 23 In U87-MG cells, autophagy and apoptosis were accompanied by increased cytoplasmic accumulation of calcium. 22 Rasul et al have demonstrated that beclin-1 is involved in evodiamine-induced autophagy in SGC-7901 cells.…”

Antioxidant activity and ultrastructural changes in gastric cancer cell lines induced by Northeastern Thai edible folk plant extracts

“…However, it is not until these phytochemicals are tested in vitro and in vivo that we can know for sure how far they can go in keeping this disease under control [31-34]. In Thailand gastric cancer is a scourge, however the unusually lower gastric cancer incidences in the Northeastern part of Thailand is of considerable interest.…”