Induction of apoptosis by ethanol extracts of Ganoderma lucidum in human gastric carcinoma cells.
Ganoderma lucidum, a well-known medicinal mushroom, is highly valued and commonly used in Oriental medicine. Although recent experimental data has revealed the proapoptotic potency of G. lucidum extracts, the underlying mechanisms of this apoptotic activity have not yet been studied in detail. In the present study, the effects of ethanol extracts of G. lucidum (EGL) on the growth of an AGS human gastric carcinoma cell line were investigated. We found that EGL treatment resulted in a dose and time-dependent significant decrease in the viability of AGS cells. This decreased viability was caused by apoptotic cell death, with observed chromatin condensation and an accumulation of apoptotic fraction. EGL treatment induced the expression of death receptor-related proteins such as death receptor 5 and tumor necrosis factor-related apoptosis-inducing ligand, which further triggered the activation of caspase-8 and the cleavage of Bid. In addition, the increase in apoptosis that was induced by EGL was correlated with activation of caspase-9 and -3, downregulation of IAP family proteins such as XIAP and survivin, and concomitant degradation of poly (ADP-ribose) polymerase. Moreover the activity of Akt was downregulated in EGL-treated cells, and the phosphatidylinositol-3 kinase/ Akt inhibitor LY294002 sensitized the cells to EGL-induced apoptosis. The results indicated that EGL induces the apoptosis of AGS cells through a signaling cascade of death receptor-mediated extrinsic, as well as mitochondria-mediated intrinsic, caspase pathways which are associated with inactivation of the Akt signal pathway.
Jang
Kyung-Jun
KJ
Department of Acupuncture and Moxibustion, College of Oriental Medicine, Dongeui University, Busan, Korea.
Han
Min-Ho
MH
Lee
Byung-Hoon
BH
Kim
Byung-Woo
BW
Kim
Cheol-Hong
CH
Yoon
Hyun-Min
HM
Choi
Yung-Hyun
YH
D017209:Apoptosis / Q000187:drug effects*; D002277:Carcinoma / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D010936:Plant Extracts / Q000494:pharmacology*; D020940:Reishi / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology*
D010936:Plant Extracts; D020169:Caspases