Suppression of Src/ERK and GSK-3/β-catenin signaling by pinosylvin inhibits the growth of human colorectal cancer cells.

Abstract

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.

• Authors: Eun-Jung Park, Hwa-Jin Chung, Hyen Joo Park, Gi Dae Kim, Yong-Hyun Ahn, Sang Kook Lee
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 55 Pg. 424-33 (May 2013) ISSN: 1873-6351 [Electronic] England
• PMID: 23333577 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Cell Cycle Proteins
• Cyclin-Dependent Kinase Inhibitor p21
• DNA Primers
• Stilbenes
• beta Catenin
• pinosylvin
• Extracellular Signal-Regulated MAP Kinases

Topics

• Cell Cycle Proteins (metabolism)
• Cell Division (drug effects)
• Cell Line, Tumor
• Colorectal Neoplasms (enzymology, metabolism, pathology)
• Cyclin-Dependent Kinase Inhibitor p21 (metabolism)
• DNA Primers
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Humans
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction
• Stilbenes (pharmacology)
• beta Catenin (metabolism)