Suillin from the mushroom Suillus placidus as potent apoptosis inducer in human hepatoma HepG2 cells.
During the search of new anti-cancer agent from high fungi, the ethyl acetate extract of the mushroom Suillus placidus was found to exhibit a significant cytotoxic activity against human hepatoma HepG2 cells. With bioassay-guided fractionation, a cytotoxic component suillin was isolated from the extract. The anti-cancer effect of suillin was subsequently examined in 8 human cancer cell lines by using MTT assay. It is of interest to note that human liver cancer cells (HepG2 cells, Hep3B cells, and SK-Hep-1) were preferentially killed by suillin with an IC(50) of approximately 2microM in a 48h treatment. Mechanistically. suillin was found for the first time to induce apoptosis in HepG2 cells as characterized by DNA fragmentation, phosphatidyl-serine (PS) externalization, activation of caspase-3, -8, -9, depolarization of mitochondrial membrane potential, as well as release of cytochrome c into the cytosol. Moreover, the apoptosis induced by suillin was suppressed by both caspase-8 and -9 inhibitors. Western blot analysis revealed significant increases in the protein levels of Fas death receptor, adaptor FADD protein, pro-apoptotic protein Bad and a decline of Bid. These results suggest that the induction of apoptosis by suillin is through both death receptor and mitochondrial pathways. Taken together, our results suggest that suillin might be an effective agent to treat liver cancer.
Liu
Fei-yan
FY
Zhejiang University, Research Centre of Siyuan Natural Pharmacy and Biotoxicology, Hangzhou, PR China. liuf64@zju.edu.cn
Luo
Ke-wang
KW
Yu
Zhi-ming
ZM
Co
Ngai-na
NN
Wu
Shi-hua
SH
Wu
Ping
P
Fung
Kwok-pui
KP
Kwok
Tim-tak
TT
D000363:Agaricales / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D006801:Humans; D010636:Phenols / Q000494:pharmacology*; D010718:Phosphatidylserines / Q000378:metabolism
D004224:Diterpenes; D010636:Phenols; D010718:Phosphatidylserines; C061636:suillin