首页> 中文期刊> 《癌症》 >倍半萜类化合物Hirsutanol激活ROS诱导肝癌细胞自噬性死亡(英文)

倍半萜类化合物Hirsutanol激活ROS诱导肝癌细胞自噬性死亡(英文)

         

摘要

Background and Objective:Hirsutanol A is a novel sesquiterpene compound purified from fungus chondrostereum sp in Sarcophyton tortuosum.Its pharmacologic effect has not been reported yet.This study aimed to investigate cytotoxic effect of Hirsutanol A on hepatocellular carcinoma(HCC) cells and its mechanism.Met hods:Hep3B cells were treated with different concentrations of Hirsutanol A.Cell proliferation was detected by MTT assay.The protein expression of LC3 was determined by Western blot.The generation of reactive oxygen species(ROS) was monitored by flow cytometry.Result s:Hirsutanol A significantly inhibited proliferation of Hep3B cells with 50% inhibition concentrations(IC50) of 14.54,6.71,and 3.59 μmol/L when exposed to Hirsutanol A for 24,48,and 72 h,respectively.Incubation of Hep3B cells with Hirsutanol A markedly increased the level of ROS and the autophagy marker MAP-LC3 conversion from type I to type II.Pre-incubation with an antioxidant N-acetyl cystein(NAC) decreased the level of ROS,and reduced MAPLC3 I-II conversion,and suppressed cell death.Blocking autophagy with a specific autophagy inhibitor 3-methyladenine(3MA),the cytotoxic effect of this compound was attenuated.Conclusion:Hirsutanol A has potent cytotoxic effect,and can induce autophagic cell death via increasing ROS production.

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