Mycelia from Antrodia camphorata in Submerged culture induce apoptosis of human hepatoma HepG2 cells possibly through regulation of Fas pathway.
The objective of this study was to investigate the antiproliferative effect and the mechanism of the methanol extracts of mycelia (MEM) form Antrodia camphorata in submerged culture toward HepG2 cells. The results showed that MEM-induced cell apoptosis involved up-regulation of Fas and down-regulation of Bcl-2, DR3, DR4, TNFRI, and TNFRII in HepG2 cells, while no changes on the levels of Bax, Bid, Bad, and Bak protein were observed. On the basis of these results, the involvement of the Fas/Fas ligand (FasL) death-receptor pathway, in MEM-induced apoptosis in HepG2 cells, was investigated. The apoptosis inducing activity was significantly enhanced by a Fas activator and inhibited by a Fas antagonist. To know about the effect of MEM on the activation of the apoptotic pathway, the adenovirus transfected with Bcl-2 was infected on HepG2 cells. The data showed that the percentage of apoptotic cells induced by MEM in Bcl-2-infected HepG2 (Bcl-2 overexpression) was not significantly different from that of uninfected HepG2. These results demonstrate that MEM induces HepG2 apoptosis through inhibition of cell growth and up-regulation of Fas/FasL to activate the pathway of caspase-3 and -8 cascades.
Song
Tuzz-Ying
TY
Department of Food Science, National Chung Hsing University, 250 Kuokuang Road, Taichung 40227, Taiwan.
Hsu
Shih-Lan
SL
Yeh
Chi-Tai
CT
Yen
Gow-Chin
GC
D017209:Apoptosis / Q000502:physiology*; D001487:Basidiomycota; D006528:Carcinoma, Hepatocellular; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D053222:Fas Ligand Protein; D019254:Genes, bcl-2 / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms; D008562:Membrane Glycoproteins / Q000502:physiology*; D025282:Mycelium / Q000502:physiology*; D014162:Transfection; D019014:fas Receptor / Q000502:physiology*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor; D020169:Caspases