Document Detail

A novel sesquiterpene Hirsutanol A induces autophagical cell death in human hepatocellular carcinoma cells by increasing reactive oxygen species.
MedLine Citation:
PMID:  20591217     Owner:  NLM     Status:  MEDLINE    
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.
METHODS: 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.
RESULTS: Hirsutanol A significantly inhibited proliferation of Hep3B cells with 50% inhibition concentrations (IC50) of 14.54, 6.71, and 3.59 micromol/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 MAP-LC3 I-II conversion, and suppressed cell death. Blocking autophagy with a specific autophagy inhibitor 3-methyladenine (3-MA), 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.
Fen Yang; You-Heng Gao; Ke-Wei Wu; Rong Deng; Dan-Dan Li; Zhi-Xiong Wei; Shan Jiang; Xiao-Qi Wu; Gong-Kan Feng; Hou-Jin Li; Xiao-Feng Zhu
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Chinese journal of cancer     Volume:  29     ISSN:  1000-467X     ISO Abbreviation:  Chin J Cancer     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-01     Completed Date:  2012-01-09     Revised Date:  2013-02-12    
Medline Journal Info:
Nlm Unique ID:  101498232     Medline TA:  Chin J Cancer     Country:  China    
Other Details:
Languages:  eng     Pagination:  655-60     Citation Subset:  IM    
State Key Laboratory of Oncology in South China, Guangzhou, Guangdong 510060, PR China.
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MeSH Terms
Acetylcysteine / pharmacology
Adenine / analogs & derivatives,  pharmacology
Agaricales / chemistry
Antineoplastic Agents / administration & dosage,  isolation & purification,  pharmacology
Autophagy / drug effects*
Carcinoma, Hepatocellular* / metabolism,  pathology
Cell Death / drug effects*
Cell Line, Tumor
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Free Radical Scavengers / pharmacology
Liver Neoplasms* / metabolism,  pathology
Microtubule-Associated Proteins / metabolism
Reactive Oxygen Species / metabolism*
Sesquiterpenes / administration & dosage,  isolation & purification,  pharmacology*
Reg. No./Substance:
0/Antineoplastic Agents; 0/Free Radical Scavengers; 0/Microtubule-Associated Proteins; 0/Reactive Oxygen Species; 0/Sesquiterpenes; 0/hirsutanol A; 0/light chain 3, human; 5142-23-4/3-methyladenine; 616-91-1/Acetylcysteine; 73-24-5/Adenine

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