Induction of G2/M arrest and apoptosis in human gastric epithelial AGS cells by aqueous extract of Agaricus blazei.
Agaricus blazei is well known as a traditional medicinal mushroom and it has been shown to exhibit immunostimulatory and anti-cancer activity. However, the cellular and molecular mechanism of cell cycle arrest and apoptosis of cancer cells is poorly understood. In this study, we have investigated whether A. blazei extract (ABE) exerts anti-proliferative and apoptotic effects on human gastric epithelial AGS cells. It was found that ABE could inhibit cell growth in a dose-dependent manner, which was associated with the arrest of G2/M phase and the induction of apoptotic cell death. Flow cytometric analysis showed that ABE could cause an arrest at the G2/M phase of the cell cycle, which is closely correlated to decreased cyclin B1 and cdc2 levels. Furthermore, this compound induced apoptosis through up-regulation of Bax and the activation of caspases with down-regulation of XIAP and cIAP-1, but not cIAP-2, and a capase-3 inhibitor could block cell death and apoptotic body formation. These data clearly indicate that ABE-induced apoptosis is associated with caspase-3 activation. In summary, the growth inhibition of ABE is highly related to cell cycle arrest at the G2/M phase and the induction of caspase-3-dependent apoptosis in human gastric epithelial AGS cells.
Jin
Cheng-Yun
CY
Department of Microbiology, College of Natural Sciences, Pusan National University, Pusan 614-714, Korea.
Choi
Yung Hyun
YH
Moon
Dong-Oh
DO
Park
Cheol
C
Park
Yeong-Min
YM
Jeong
Sang-Cheol
SC
Heo
Moon-Soo
MS
Lee
Tae-Ho
TH
Lee
Jae-Dong
JD
Kim
Gi-Young
GY
D000364:Agaricus / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D016203:CDC2 Protein Kinase / Q000187:drug effects; D020169:Caspases / Q000187:drug effects; D002457:Cell Extracts / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019926:Cyclin B / Q000187:drug effects; D056744:Cyclin B1; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000187:drug effects; D013274:Stomach Neoplasms / Q000378:metabolism*; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000187:drug effects
D000970:Antineoplastic Agents; C534699:CCNB1 protein, human; D002457:Cell Extracts; D019926:Cyclin B; D056744:Cyclin B1; D051034:Inhibitor of Apoptosis Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; D051028:bcl-2-Associated X Protein; D016203:CDC2 Protein Kinase; D020169:Caspases