Suppression of Src/ERK and GSK-3/β-catenin signaling by pinosylvin inhibits the growth of human colorectal cancer cells.
Pinosylvin, a naturally occurring trans-stilbenoid mainly found in Pinus species, has exhibited a potential cancer chemopreventive activity. However, the growth inhibitory activity against cancer cells and the underlying molecular mechanisms remain to be elucidated. Therefore, the anti-proliferative activity of pinosylvin was investigated in human colorectal HCT 116 cancer cells. Pinosylvin inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53. Pinosylvin was also found to attenuate the activation of proteins involved in focal adhesion kinase (FAK)/c-Src/extracellular signal-regulated kinase (ERK) signaling, and phosphoinositide 3-kinase (PI3K)/Akt/ glycogen synthase kinase 3β (GSK-3β) signaling pathway. Subsequently, pinosylvin suppressed the nuclear translocation of β-catenin, one of downstream molecules of PI3K/Akt/GSK-3β signaling, and these events led to the sequential downregulation of β-catenin-mediated transcription of target genes including BMP4, ID2, survivin, cyclin D1, MMP7, and c-Myc. These findings demonstrate that the anti-proliferative activity of pinosylvin might be associated with the cell cycle arrest and downregulation of cell proliferation regulating signaling pathways in human colorectal cancer cells.
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CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-Y GENE-N GENE-N GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-N GENE-N GENE-N GENE-N GENE-N GENE-Y GENE-Y GENE-Y GENE-N GENE-N GENE-Y
Pinosylvin pinosylvin pinosylvin trans-stilbenoid Pinosylvin Pinosylvin phosphoinositide pinosylvin pinosylvin β-catenin PI3K Akt GSK-3β β-catenin BMP4 ID2 survivin cyclin D1 MMP7 c-Myc cyclin D1 cyclin E cyclin A cyclin dependent kinase 2 CDK2 CDK4 c-Myc retinoblastoma protein pRb p21 WAF1 CIP1 p53 ocal adhesion kinase FAK c-Src extracellular signal-regulated kinase ERK phosphoinositide 3-kinase PI3K Akt glycogen synthase kinase 3β GSK-3β Src ERK GSK-3 β-catenin