Epigallocatechin-3-gallate (EGCG) inhibits PC-3 prostate cancer cell proliferation via MEK-independent ERK1/2 activation.

Abstract

Epigallocatechin-3-gallate (EGCG), a tea polyphenol, inhibits the proliferation of many cancer cell lines; however, the antiproliferative mechanism(s) are not well-characterized. The objective of this study is to identify the cellular signaling mechanism(s) responsible for the antiproliferative effects of EGCG in the PC-3 prostate cancer cell line. EGCG inhibited PC-3 cell proliferation in a concentration-dependent manner with an IC(50) value of 39.0 microM, but had no effect on the proliferation of a nontumorigenic prostate epithelial cell line (RWPE-1). Treatment of PC-3 cells with EGCG (0-50 microM) resulted in time and concentration-dependent activation of the extracellular signal-regulated kinase (ERK1/2) pathway. EGCG treatment did not induce ERK1/2 activity in RWPE-1 cells. The activation of ERK1/2 by EGCG was not inhibited using PD98059, a potent inhibitor of mitogen-activated protein kinase kinase (MEK), the immediate upstream kinase responsible for ERK1/2 activation; suggesting a MEK-independent signaling mechanism. Pretreatment of PC-3 cells with a phosphoinositide-3 kinase (PI3K) inhibitor partially reduced both EGCG-induced ERK1/2 activation and the antiproliferative effects of this polyphenol. These results suggest that ERK1/2 activation via a MEK-independent, PI3-K-dependent signaling pathway is partially responsible for the antiproliferative effects of EGCG in PC-3 cells.

• Authors: Daniel S Albrecht, Elizabeth A Clubbs, Mario Ferruzzi, Joshua A Bomser
• Journal: Chemico-biological interactions (Chem Biol Interact) Vol. 171 Issue 1 Pg. 89-95 (Jan 10 2008) ISSN: 0009-2797 [Print] Ireland
• PMID: 17931610 (Publication Type: Journal Article)

Chemical References

• Anticarcinogenic Agents
• Chromones
• Flavonoids
• Morpholines
• Phosphoinositide-3 Kinase Inhibitors
• Protein Kinase Inhibitors
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
• Catechin
• epigallocatechin gallate
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• Mitogen-Activated Protein Kinase Kinases
• 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

Topics

• Anticarcinogenic Agents (pharmacology)
• Catechin (analogs & derivatives, pharmacology)
• Cell Line
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Chromones (pharmacology)
• Enzyme Activation (drug effects)
• Epithelial Cells (drug effects, metabolism)
• Flavonoids (pharmacology)
• Humans
• Inhibitory Concentration 50
• Male
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Mitogen-Activated Protein Kinase Kinases (antagonists & inhibitors, metabolism)
• Morpholines (pharmacology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphoinositide-3 Kinase Inhibitors
• Phosphorylation (drug effects)
• Prostatic Neoplasms (metabolism, pathology)
• Protein Kinase Inhibitors (pharmacology)