Involvement of Mitochondrial Pathway in Triptolide-Induced Cytotoxicity in Human Normal Liver L-02 Cells(Pharmacology)

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概要

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• Triptolide, a purified diterpenoid triepoxide compound derived from a traditional Chinese medicine, Tripterygium wilfordii HOOK, f (TWHf), has been used in the treatment of autoimmune and inflammatory diseases. However, the toxicity of triptolide limits its application to a great extent. In the present study, we treated human normal liver L-02 cells (L-02 cells) with triptolide in vitro and investigated its toxic effects. The cytotoxicity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliuni bromide (MTT) assay for cellular viability and by flow cytometry and Hoechst 33258 staining for apoptosis. The mitochondrial membrane potential (Δψm) was evaluated by flow cytometry with JC-1 as probe. After treatment with triptolide, a decrease in the viability of L-02 cells and increase in apoptosis were observed. Triptolide-induced apoptosis was accompanied by loss of mitochondrial membrane potential and release of cytochrome c (cyt-c) from the mitochondria to the cytosol and down-regulation of anti-apoptotic protein Bcl-2 levels with concurrent up-regulation in pro-apoptotic protein Bax levels and tumor suppressor protein p53 levels. Triptolide-increased activity of caspase 9 and caspase 3 was also observed. These results indicate that triptolide induced cytotoxicity in L-02 cells by apoptosis, which is mediated through mitochondrial pathway.

• 公益社団法人日本薬学会の論文
• 2008-04-01

著者

• He Ling

  Department Of Chemistry Zhejiang University

• He Ling

  Department Of Pharmaceutics School Of Pharmacy Shenyang Pharmaceutical University

• LI Fu

  Department of Pharmacology, China Pharmaceutical University

• ZHANG Luyong

  National Drug Screening Center, China Pharmaceutical University

• Duan Weigang

  Department Of Pharmacology Yunan University Of Traditional Chinese Medicine

• Liu Chunhui

  National Center Of Drug Screening China Pharmaceutical University

• Li Fu

  Department Of Pharmacology China Pharmaceutical University

• Zhang Luyong

  National Center Of Drug Screening China Pharmaceutical University

• YAO Jincheng

  National Center of Drug Screening, China Pharmaceutical University

• JIANG Zhenzhou

  National Center of Drug Screening, China Pharmaceutical University

• HUANG Jingfeng

  National Center of Drug Screening, China Pharmaceutical University

• HU Ling

  Clinical Pharmacy Research Institute, the Second Xiangya Hospital of Central South University

• XIAO Yajie

  National Center of Drug Screening, China Pharmaceutical University

• SHU Bin

  National Center of Drug Screening, China Pharmaceutical University

• Shu Bin

  National Center Of Drug Screening China Pharmaceutical University

• Hu Ling

  Clinical Pharmacy Research Institute The Second Xiangya Hospital Of Central South University

• Xiao Yajie

  National Center Of Drug Screening China Pharmaceutical University

• Yao Jincheng

  National Center Of Drug Screening China Pharmaceutical University

• Jiang Zhenzhou

  National Center Of Drug Screening China Pharmaceutical University:key Laboratory Of Drug Quality Con

• Huang Jingfeng

  National Center Of Drug Screening China Pharmaceutical University

• Jiang Zhenzhou

  New Drug Screening Center China Pharmaceutical University

• Li Fu

  Department Of Breast Cancer Pathology Tianjin Medical University

• Li Zhan

  New Drug Screening Center China Pharmaceutical University

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