Molecular mechanism of apoptosis induced by schizandrae-derived lignans in human leukemia HL-60 cells

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• 作者：Shigang Lin ; Makoto Fujii ; De-Xing Hou
• 关键词：Schizandrae ; Lignan ; Apoptosis ; Caspase ; Mitochondria ; HL-60 cells
• 刊名：Food and Chemical Toxicology
• 出版年：2008
• 出版时间：February 2008
• 年：2008
• 卷：46
• 期：2
• 页码：590-597
• 全文大小：498 K

文摘

Schizandrae chinensis, a traditional Chinese medicine herb, has been used to treat hepatitis B disease in Chinese hospital clinic. We have isolated two bioactive compounds, deoxyschizandrin and γ-schizandrin, from S. chinensis. In the present, we reported that deoxyschizandrin and γ-schizandrin could induce apoptosis in human promyelocytic leukemia cells (HL-60), as characterized by DNA fragmentation and poly (ADP) ribose polymerase (PARP) cleavage. Further molecular analysis showed that deoxyschizandrin and γ-schizandrin caused the loss of mitochondrial membrane potential (ΔΨm), cytochrome c release from mitochondrion to cytosol, truncation of Bid protein, and activation of caspase-3 and -9. However, they did not increase the intracellular level of reactive oxygen species (ROS). Antioxidants such as N-acetyl cysteine (NAC) and catalase did not block the apoptosis induced by deoxyschizandrin or γ-schizandrin. These findings suggest that deoxyschizandrin and γ-schizandrin-induced apoptosis in HL-60 cells involved ROS-independent mitochondrial dysfunction pathway.