In:
Journal of Cellular Biochemistry, Wiley, Vol. 104, No. 6 ( 2008-08-15), p. 2131-2142
Abstract:
Cyclooxygenase‐2 (COX‐2) content is increased in many types of tumor cells. We have investigated the mechanism by which resveratrol, a stilbene that is pro‐apoptotic in many tumor cell lines, causes apoptosis in human head and neck squamous cell carcinoma UMSCC‐22B cells by a mechanism involving cellular COX‐2. UMSCC‐22B cells treated with resveratrol for 24 h, with or without selected inhibitors, were examined: (1) for the presence of nuclear activated ERK1/2, p53 and COX‐2, (2) for evidence of apoptosis, and (3) by chromatin immunoprecipitation to demonstrate p53 binding to the p21 promoter. Stilbene‐induced apoptosis was concentration‐dependent, and associated with ERK1/2 activation, serine‐15 p53 phosphorylation and nuclear accumulation of these proteins. These effects were blocked by inhibition of either ERK1/2 or p53 activation. Resveratrol also caused p53 binding to the p21 promoter and increased abundance of COX‐2 protein in UMSCC‐22B cell nuclei. Resveratrol‐induced nuclear COX‐2 accumulation was dependent upon ERK1/2 activation, but not p53 activation. Activation of p53 and p53‐dependent apoptosis were blocked by the COX‐2 inhibitor, NS398, and by transfection of cells with COX‐2‐siRNA . In UMSCC‐22B cells, resveratrol‐induced apoptosis and induction of nuclear COX‐2 accumulation share dependence on the ERK1/2 signal transduction pathway. Resveratrol‐inducible nuclear accumulation of COX‐2 is essential for p53 activation and p53‐dependent apoptosis in these cancer cells. J. Cell. Biochem. 104: 2131–2142, 2008. © 2008 Wiley‐Liss, Inc.
Type of Medium:
Online Resource
ISSN:
0730-2312
,
1097-4644
Language:
English
Publisher:
Wiley
Publication Date:
2008
detail.hit.zdb_id:
1479976-5
SSG:
12
