Calf Spleen Extractive Injection (CSEI), a small peptides enriched extraction, induces human hepatocellular carcinoma cell apoptosis via ROS/MAPKs dependent mitochondrial pathway

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• 作者：Dongxu Jia^a ; ^{jiadx14@mails.jlu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Wenqian Lu^a ; ^{luwq15@mails.jlu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Xinrui Zhang^a ; ^{xrzhang15@mails.jlu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Guangsheng Cai^a ; ^{caigs15@mails.jlu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Lirong Teng^a ; ^{tenglr543@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Xinyu Wang^a ; ^{wangxy1313@mails.jlu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Minghai Zhang^a ; ^{zhangmh9913@mails.jlu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Yan Zeng^b ; ^{zengyang_aodong@126.com" class="auth_mail" title="E-mail the corresponding author} ; Chunhua Liang^c ; ^{982981710@qq.com" class="auth_mail" title="E-mail the corresponding author} ; Di Wang^a ; ^{jluwangdi@outlook.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Calf Spleen Extractive Injection (CSEI) ; Apoptosis ; Hepatocellular carcinoma ; ROS/MAPKs ; Mitochondria
• 刊名：Journal of Pharmacological Sciences
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：132
• 期：2
• 页码：122-130
• 全文大小：2831 K

文摘

Calf Spleen Extractive Injection (CSEI), a small peptides enriched extraction, performs immunomodulatory activity on cancer patients suffering from radiotherapy or chemotherapy. The present study aims to investigate the anti-hepatocellular carcinoma effects of CSEI in cells and tumor-xenografted mouse models. In HepG2 and SMMC-7721 cells, CSEI reduced cell viability, enhanced apoptosis rate, caused reactive oxygen species (ROS) accumulation, inhibited migration ability, and induced caspases cascade and mitochondrial membrane potential dissipation. CSEI significantly inhibited HepG2-xenografted tumor growth in nude mice. In cell and animal experiments, CSEI increased the activations of pro-apoptotic proteins including caspase 8, caspase 9 and caspase 3; meanwhile, it suppressed the expressions of anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) and anti-oxidation proteins, such as nuclear factor-erythroid 2 related factor 2 (Nrf2) and catalase (CAT). The enhanced phosphorylation of P38 and c-JunN-terminalkinase (JNK), and decreased phosphorylation of extra cellular signal-regulated protein kinase (ERKs) were observed in CSEI-treated cells and tumor tissues. CSEI-induced cell viability reduction was significantly attenuated by N-Acetyl-l-cysteine (a ROS inhibitor) pretreatment. All data demonstrated that the upregulated oxidative stress status and the altered mitogen-activated protein kinases (MAPKs) phosphorylation contributed to CSEI-driven mitochondrial dysfunction. Taken together, CSEI exactly induced apoptosis in human hepatocellular carcinoma cells via ROS/MAPKs dependent mitochondrial pathway.