PMID- 20591217 OWN - NLM STAT- MEDLINE DCOM- 20120109 LR - 20210617 IS - 1000-467X (Print) IS - 1944-446X (Linking) VI - 29 IP - 7 DP - 2010 Jul TI - A novel sesquiterpene Hirsutanol A induces autophagical cell death in human hepatocellular carcinoma cells by increasing reactive oxygen species. PG - 655-60 AB - 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. FAU - Yang, Fen AU - Yang F AD - State Key Laboratory of Oncology in South China, Guangzhou, Guangdong 510060, PR China. FAU - Gao, You-Heng AU - Gao YH FAU - Wu, Ke-Wei AU - Wu KW FAU - Deng, Rong AU - Deng R FAU - Li, Dan-Dan AU - Li DD FAU - Wei, Zhi-Xiong AU - Wei ZX FAU - Jiang, Shan AU - Jiang S FAU - Wu, Xiao-Qi AU - Wu XQ FAU - Feng, Gong-Kan AU - Feng GK FAU - Li, Hou-Jin AU - Li HJ FAU - Zhu, Xiao-Feng AU - Zhu XF LA - eng PT - Journal Article PL - England TA - Chin J Cancer JT - Chinese journal of cancer JID - 101498232 RN - 0 (Antineoplastic Agents) RN - 0 (Free Radical Scavengers) RN - 0 (MAP1LC3A protein, human) RN - 0 (Microtubule-Associated Proteins) RN - 0 (Reactive Oxygen Species) RN - 0 (Sesquiterpenes) RN - 0 (hirsutanol A) RN - 5142-23-4 (3-methyladenine) RN - JAC85A2161 (Adenine) RN - WYQ7N0BPYC (Acetylcysteine) SB - IM MH - Acetylcysteine/pharmacology MH - Adenine/analogs & derivatives/pharmacology MH - Agaricales/chemistry MH - Antineoplastic Agents/administration & dosage/isolation & purification/pharmacology MH - Autophagy/*drug effects MH - *Carcinoma, Hepatocellular/metabolism/pathology MH - Cell Death/*drug effects MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - Dose-Response Relationship, Drug MH - Free Radical Scavengers/pharmacology MH - Humans MH - *Liver Neoplasms/metabolism/pathology MH - Microtubule-Associated Proteins/metabolism MH - Reactive Oxygen Species/*metabolism MH - Sesquiterpenes/administration & dosage/isolation & purification/*pharmacology EDAT- 2010/07/02 06:00 MHDA- 2012/01/10 06:00 CRDT- 2010/07/02 06:00 PHST- 2010/07/02 06:00 [entrez] PHST- 2010/07/02 06:00 [pubmed] PHST- 2012/01/10 06:00 [medline] AID - 1944-446X201007655 [pii] AID - 10.5732/cjc.009.10702 [doi] PST - ppublish SO - Chin J Cancer. 2010 Jul;29(7):655-60. doi: 10.5732/cjc.009.10702.