期刊
INTERNATIONAL JOURNAL OF ONCOLOGY
卷 40, 期 3, 页码 816-824出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2011.1246
关键词
cell cycle; phosphatidylinositol 3-kinase; Akt; p21; p27; brassinin
类别
资金
- Japanese Ministry of Education, Culture, Sports, Science and Technology
- Japan Society for the Promotion of Science
- Grants-in-Aid for Scientific Research [23790669, 21249042] Funding Source: KAKEN
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.
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