Ethanol enhances cucurbitacin B-induced apoptosis by inhibiting cucurbitacin B-induced autophagy in LO2 hepatocytes

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• 作者：Qian Ding ; Jiaolin Bao ; Wenwen Zhao ; Jinjian Lu…
• 关键词：Ethanol ; Cucurbitacin B ; Autophagy ; Apoptosis ; Hepatocyte
• 刊名：Molecular & Cellular Toxicology
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：12
• 期：1
• 页码：29-36
• 全文大小：6,026 KB
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• 作者单位：Qian Ding (1) (2)
  Jiaolin Bao (1)
  Wenwen Zhao (1)
  Jinjian Lu (1)
  Hong Zhu (3)
  Xiuping Chen (1)
  
  1. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
  2. GuiYang College of Traditional Chinese Medicine, Guiyang, Guizhou, 550025, China
  3. Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, 310058, China
  
• 刊物主题：Cell Biology; Pharmacology/Toxicology;
• 出版者：Springer Netherlands
• ISSN：2092-8467

文摘

Ethanol is a common risk factor for liver injury. Cucurbitacin B (CuB) is a natural product with potent cytotoxic activities mediated by inducing apoptosis. This study investigated the effect of ethanol on CuB-induced cytotoxicity in LO2 hepatocytes. Low concentration of ethanol alone showed no significant cytotoxic effect on LO2 cells. CuB dose-dependently decreased cell viability. However, ethanol co-treatment significantly enhanced CuB-induced cytotoxicity. CuB-induced mitochondria membrane potential (ΔΨ) depolarization was further decreased by ethanol. Furthermore, CuB-induced apoptosis was augmented by ethanol, as evidenced by DNA fragmentation, Annexin V staining, and apoptotic protein expression. Ethanol inhibited CuB-induced autophagy, as determined by MDC staining, autophagic protein expression, and transmission electron microscopy. Therefore, the present data suggested that ethanol enhanced CuB cytotoxicity in LO2 hepatocytes, which was mediated by inhibiting autophagy and augmenting apoptosis.