Physalis peruviana extract induces apoptosis in human Hep G2 cells through CD95/CD95L system and the mitochondrial signaling transduction pathway.
Physalis species is a popular folk medicine used for treating cancer, leukemia, hepatitis and other diseases. Studies have shown that the ethanol extract of Physalis peruviana (EEPP) inhibits growth and induces apoptotic death of human Hep G2 cells in culture, whereas proliferation of the mouse BALB/C normal liver cells was not affected. In this study, we performed detailed studies to define the molecular mechanism of EEPP-induced apoptosis in Hep G2 cells. The results further confirmed that EEPP inhibited cell proliferation in a dose- and time-dependent manner. At 50 microg/ml, EEPP significantly increased the accumulation of the sub-G1 peak (hypoploid) and the portion of apoptotic annexin V positive cells. EEPP was found to trigger apoptosis through the release of cytochrome c, Smac/DIABLO and Omi/HtrA2 from mitochondria to cytosol and consequently resulted in caspase-3 activation. Pre-treatment with a general caspase inhibitor (z-VAD-fmk) prevented cytochrome c release. After 48 h of EEPP treatment, the apoptosis of Hep G2 cells was found to associate with an elevated p53, and CD95 and CD95L proteins expression. Furthermore, a marked down-regulation of the expression of the Bcl-2, Bcl-XL and XIAP, and up-regulation of the Bax and Bad proteins were noted. Taken together, the present results suggest that EEPP-induced Hep G2 cell apoptosis was possibly mediated through the CD95/CD95L system and the mitochondrial signaling transduction pathway.
Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
Shu-Jing
SJ
Wu
Lean-Teik
LT
Ng
Doung-Liang
DL
Lin
Shan-Ney
SN
Huang
Shyh-Shyan
SS
Wang
Chun-Ching
CC
Lin
D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D003574:Cytochrome c Group / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D053222:Fas Ligand Protein; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D032321:Physalis / Q000737:chemistry*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000378:metabolism*
D003574:Cytochrome c Group; D004365:Drugs, Chinese Herbal; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D019014:fas Receptor; C076615:cytochrome c''