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The phosphatidylinositol 3-kinase (PI3K) signaling pathway is activatedin a broad spectrum of human cancers, including colon cancer. The natural productbrassinin is a type of indole compound derived from cruciferous vegetables, andhas been shown to have anti-proliferative effects against cancer for both in vivoand in vitro models. Here, we show for the first time that brassinin inhibitscell growth in human colon cancer cells by arresting the cell cycle at the G1phase via inhibition of the PI3K signaling pathway. Brassinin increased the expressionof p21 and p27, resulting in hypophosphorylation of the retinoblastoma gene (RB).Knockdown of p21 or p27 by each siRNA significantly repressed G1 phase arrestinduced by brassinin. The increase of p21 and p27 was associated with inhibitionof the PI3K signaling pathway. In addition, exogenous expression of constitutivelyactive Akt represses the cell cycle arrest at G1 phase induced by brassinin. Theseresults suggest the possibility that brassinin inhibits the PI3K signaling pathwayand upregulates the expression of p21 and p27, thereby inducing G1 phase arrest.

international journal of oncology

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