In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 4138-4138
Abstract:
Resveratrol is a naturally-occurring trihydroyxl-diphenylethylene compound that has been shown experimentally to have beneficial effects in the treatment of cancer and cardiovascular disease. We have studied the molecular basis of the anti-cancer actions of resveratrol, using human ovarian carcinoma (OVCAR-3) cells. Resveratrol induces programmed cell death (apoptosis) in these cells and activates important signal transducing proteins including extracellular signal-regulated kinases 1 and 2 (ERK1/2) in cancer cells. Resveratrol also causes nuclear accumulation of the enzyme cyclooxygenase-2 (COX-2) and of the oncogene suppressor protein, p53. Expressed constitutively, cytoplasmic COX-2 is a marker of tumor cell aggressiveness, but there is a resveratrol-inducible pool of nuclear COX-2 that is important to activation (Ser-15 phosphorylation) of the oncogene suppressor protein, p53. Our findings include the following: (1) Nuclear accumulation of COX-2 in resveratrol-treated cells is blocked by the ERK1/2 inhibitor, PD98059. (2) An inhibitor of COX-2 activity, NS398, prevents accumulation in the nucleus of ERK1/2, COX-2, activated p53 and SUMO-1. (3) Apoptosis, quantitated by nucleosome ELISA and the nuclear abundance of the pro-apoptotic protein, Bcl-xs, were inhibited by NS398. This finding implicates nuclear COX-2 in p53-mediated apoptosis induced by resveratrol. Sumoylation is important to stabilization of p53 and a COX-2/SUMO-1 interaction suggests sumoylation of COX-2 in resveratrol-treated cells. (4) Chromatin immunoprecipitation (ChIP) studies showed binding of induced nuclear COX-2 to the promoter region of p21, a pro-apoptotic gene target of transcriptionally active p53. In summary, nuclear accumulation of activated ERK1/2 and COX-2 are essential to resveratrol-induced, pSer-15-p53-mediated apoptosis in human ovarian cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4138.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM10-4138
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2010
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
