Brassinin induces G1 phase arrest through increase of p21 and p27 by             inhibition of the phosphatidylinositol 3-kinase signaling pathway in human colon             cancer cells.
The phosphatidylinositol 3-kinase (PI3K) signaling pathway is activated             in a broad spectrum of human cancers, including colon cancer. The natural product             brassinin is a type of indole compound derived from cruciferous vegetables, and             has been shown to have anti-proliferative effects against cancer for both in vivo             and in vitro models. Here, we show for the first time that brassinin inhibits             cell growth in human colon cancer cells by arresting the cell cycle at the G1             phase via inhibition of the PI3K signaling pathway. Brassinin increased the expression             of p21 and p27, resulting in hypophosphorylation of the retinoblastoma gene (RB).             Knockdown of p21 or p27 by each siRNA significantly repressed G1 phase arrest             induced by brassinin. The increase of p21 and p27 was associated with inhibition             of the PI3K signaling pathway. In addition, exogenous expression of constitutively             active Akt represses the cell cycle arrest at G1 phase induced by brassinin. These             results suggest the possibility that brassinin inhibits the PI3K signaling pathway             and upregulates the expression of p21 and p27, thereby inducing G1 phase arrest.
Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan.
Yasuyuki
Y
Izutani
Shingo
S
Yogosawa
Yoshihiro
Y
Sowa
Toshiyuki
T
Sakai
D059447:Cell Cycle Checkpoints / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism*; D016193:G1 Phase / Q000187:drug effects* / Q000235:genetics; D019073:HT29 Cells; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D016160:Retinoblastoma Protein / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013859:Thiocarbamates / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D000094162:Phytoalexins
D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D007211:Indoles; D058539:Phosphatidylinositol 3-Kinase; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D013859:Thiocarbamates; C493956:CDKN1A protein, human; C089020:brassinin; D000094162:Phytoalexins