Molecular mechanism of apoptosis induced by schizandrae-derived lignans in human leukemia HL-60 cells.
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 gamma-schizandrin, from S. chinensis. In the present, we reported that deoxyschizandrin and gamma-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 gamma-schizandrin caused the loss of mitochondrial membrane potential (DeltaPsim), 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 gamma-schizandrin. These findings suggest that deoxyschizandrin and gamma-schizandrin-induced apoptosis in HL-60 cells involved ROS-independent mitochondrial dysfunction pathway.
Lin
Shigang
S
Department of Biochemical Science and Technology, Faculty of Agriculture, Kagoshima University, Korimoto 1-21-24, Kagoshima 890-0065, Japan.
Fujii
Makoto
M
Hou
De-Xing
DX
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects*; D034242:Cyclooctanes / Q000302:isolation & purification / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D017705:Lignans / Q000302:isolation & purification / Q000494:pharmacology*; D008967:Molecular Biology; D008517:Phytotherapy / Q000379:methods*; D028321:Plant Preparations / Q000302:isolation & purification / Q000494:pharmacology*; D011083:Polycyclic Compounds / Q000302:isolation & purification / Q000494:pharmacology*; D032141:Schisandra; D013329:Structure-Activity Relationship
D034242:Cyclooctanes; D017705:Lignans; D028321:Plant Preparations; D011083:Polycyclic Compounds; D053148:Caspase 3; C011105:schizandrin