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

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Abstract

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.

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Authors and Affiliations

  1. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China

    Qian Ding, Jiaolin Bao, Wenwen Zhao, Jinjian Lu & Xiuping Chen

  2. GuiYang College of Traditional Chinese Medicine, Guiyang, Guizhou, 550025, China

    Qian Ding

  3. Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, 310058, China

    Hong Zhu

Authors
  1. Qian Ding
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  2. Jiaolin Bao
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  3. Wenwen Zhao
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  5. Hong Zhu
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  6. Xiuping Chen
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Correspondence to Xiuping Chen.

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Ding, Q., Bao, J., Zhao, W. et al. Ethanol enhances cucurbitacin B-induced apoptosis by inhibiting cucurbitacin B-induced autophagy in LO2 hepatocytes. Mol. Cell. Toxicol. 12, 29–36 (2016). https://doi.org/10.1007/s13273-016-0005-2

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  • DOI: https://doi.org/10.1007/s13273-016-0005-2

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