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Time‐dependent resveratrol‐mediated mRNA and protein expression associated with cell cycle in WR‐21 cells containing mutated human c‐Ha‐Ras
Author(s) -
Young Leeanne F.,
Martin Keith R.
Publication year - 2006
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.200500149
Subject(s) - resveratrol , cell cycle , biology , microbiology and biotechnology , cyclin b1 , transcription (linguistics) , oncogene , cell cycle checkpoint , mitosis , messenger rna , cyclin a , gene expression , cell growth , apoptosis , gene , cyclin , cyclin dependent kinase 1 , biochemistry , linguistics , philosophy
Cancer results from an undesirable imbalance between cellular proliferation and apoptosis. Both processes may be modulated at the level of gene expression, viz., p53 and c‐Ha‐ras, by dietary bioactive components such as resveratrol. We tested the time‐dependent effect of resveratrol on gene and protein expression in WR‐21 cells containing a mutated human c‐Ha‐ras oncogene. We demonstrate cyclic resveratrol‐mediated expression of p53, mdm2, p21 cip/waf , Rb, and cyclin G at both the RNA and the protein level at < 8 h. However, ras was not differentially expressed at either the RNA or the protein level. p53 was upregulated followed by p21 cip/waf , then mdm2, and cyclin G, all downstream p53‐activated targets. RNA transcription increased at > 8 h for all genes except p53, but protein levels did not suggest uncoupling of transcription and translation. At 24 h, both p53 and Rb expression returned to baseline, suggesting collapse of DNA structure and spindle assembly checkpoints characteristic of mitotic catastrophe. In summary, resveratrol at < 8 h induced p53‐mediated effects, including apoptosis and cell‐cycle arrest (G2/M). However, later, it induced cell‐cycle checkpoint dysfunction, indicative of mitotic catastrophe. Thus, future studies should better elucidate the temporal mechanism of the dietary bioactive agent resveratrol on cancer cells.