Genistein induces G2/M arrest in gastric cancer cells by increasing the tumor suppressor PTEN expression.
Genistein, a major isoflavone found in soybeans, exhibits anticarcinogenic properties. The inhibitory effect of genistein on cell proliferation is associated with G2/M cell cycle arrest and inhibition of cdc2 activities. Here we assessed the role of PTEN in regulation of genistein-mediated G2/M cell cycle arrest in the gastric cancer cell lines (SGC-7901 and BGC-823). After 24 h following treatment, genistein induced a concentration-dependent accumulation of cells in the G2/M phase of the cell cycle. The sustained G2/M arrest by genistein in SGC-7901 and BGC-823 cells is associated with increased phospho-cdc2 (Tyr15) and decreased cdc2 protein. Genistein treatment increased Wee1 levels and decreased phospho-Wee1 (Ser 642). Moreover, genistein substantially decreased the Ser473 and Thr308 phosphorylation of Akt and upregulated PTEN expression. Downregulation of PTEN by siRNA in genistein-treated cells increased phospho-Wee1 (Ser642), whereas decreased phospho-Cdc2 (Tyr15), resulting in decreased the G2/M cell cycle arrest. Therefore, induction of G2/M cell cycle arrest by genistein involved upregulation of PTEN.
a Department of Colorectal Surgery , the Third Affiliated Hospital of Harbin Medical University , Harbin , China.
Yan-Long
YL
Liu
Guo-Qiang
GQ
Zhang
Yue
Y
Yang
Chun-Yan
CY
Zhang
Rong-Xia
RX
Fu
Yan-Mei
YM
Yang
D016203:CDC2 Protein Kinase; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D018844:Cyclin-Dependent Kinases; D015536:Down-Regulation; D016195:G2 Phase / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism*; D015854:Up-Regulation
D018797:Cell Cycle Proteins; D019926:Cyclin B; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D019833:Genistein; D011505:Protein-Tyrosine Kinases; C499349:WEE1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human