Ginsenoside Rg5 induces G2/M phase arrest, apoptosis and autophagy via regulating ROS-mediated MAPK pathways against human gastric cancer

被引:83
作者
Liu, Yannan [1 ,2 ,3 ]
Fan, Daidi [1 ,2 ,3 ]
机构
[1] Northwest Univ, Sch Chem Engn, Shaanxi Key Lab Degradable Biomed Mat, 229 North Taibai Rd, Xian 710069, Shaanxi, Peoples R China
[2] Northwest Univ, Sch Chem Engn, Shaanxi R&D Ctr Biomat & Fermentat Engn, 229 North Taibai Rd, Xian 710069, Shaanxi, Peoples R China
[3] Northwest Univ, Biotech & Biomed Res Inst, Taibai North Rd 229, Xian 710069, Shaanxi, Peoples R China
基金
中国国家自然科学基金;
关键词
Ginsenoside Rg5; Apoptosis; Autophagy; ROS; MAPK; Human gastric cancer; CELL-CYCLE ARREST; IN-VITRO; SIGNALING PATHWAYS; ANTITUMOR-ACTIVITY; DIALLYL DISULFIDE; CARCINOMA CELLS; P38; MAPK; DEATH; ACTIVATION; INDUCTION;
D O I
10.1016/j.bcp.2019.07.008
中图分类号
R9 [药学];
学科分类号
100702 [药剂学];
摘要
Ginsenoside Rg5, a rare saponin belonging to the family of protopanaxadiol ginsenosides, has been demonstrated to have potential anti-tumor effects in various cancers. However, the effect of Rg5 on human gastric cancer and the underlying molecular mechanisms remain to be elucidated. In this study, Rg5 could suppress cell proliferation by causing G2/M phase arrest. Treatment with Rg5 could induce apoptosis through the extrinsic death receptor and intrinsic mitochondrial pathways. Autophagy induction was demonstrated by the formation of autophagosomes and autophagy-related proteins. Rg5-induced cell death was inhibited by the autophagy inhibitor 3-MA and apoptosis inhibitor Z-VAD-FMK. Moreover, the suppression of apoptosis weakened Rg5-induced autophagy, while the inhibition of autophagy attenuated Rg5-induced apoptosis. Further studies revealed that Rg5 induced ROS production and activated MAPK signaling pathways. The ROS scavenger NAC markedly diminished G2/M arrest, apoptosis, autophagy and activation of MAPK pathways induced by Rg5. The p38 inhibitor SB203580 or knockdown of p38 by siRNA clearly reversed Rg5-induced apoptosis and G2/M arrest. The JNK inhibitor SP600125 or knockdown of JNK by siRNA markedly attenuated Rg5-induced G2/M arrest, apoptosis and autophagy. The inhibition of ERK inhibitor U0126 or knockdown of ERK by siRNA clearly restored Rg5-induced apoptosis and autophagy. Finally, Rg5 significantly suppressed the growth of xenograft gastric tumors with fewer side effects. Overall, the evidence suggested that Rg5 is a novel and promising strategy for the treatment of gastric cancer owing to its high efficacy, multiple mechanisms and fewer side effects.
引用
收藏
页码:285 / 304
页数:20
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