Resveratrol interferes with AKT activity and triggers apoptosis in human uterine cancer cells.
BACKGROUND
Endometrial cancer is the fourth most prominent cancer among all feminine cancers in the Western world. Resveratrol, a natural anti-oxidant found in red wine emerging as a novel anticancer agent, exerts antiproliferative and pro-apoptotic activity in various cancer cell types, but its effect on uterine cancer cells is poorly understood. At the molecular level, resveratrol has been reported to inhibit cyclooxygenase (COX) expression and/or activity; in endometrial cancer cells, COX-2 is overexpressed and confers cellular resistance to apoptosis. The aim of the present study was to determine if resveratrol could exert anti-proliferative and pro-apoptotic activity over uterine cancer cells upon inhibition of COX-2 expression and/or activity. Six different human uterine cancer cell lines were used as a model (HeLa, Hec-1A, KLE, RL95-2, Ishikawa and EN-1078D).


CONCLUSIONS
High-dose of resveratrol triggered apoptosis in five out of six uterine cancer cell lines, as judged from Hoechst nuclear staining and effector caspase cleavage. In accordance, uterine cancer cell proliferation was decreased. Resveratrol also reduced cellular levels of the phosphorylated/active form of anti-apoptotic kinase AKT. Endogenous COX-2 protein levels were decreased, concomitant with a decrease in production of COX metabolites PGE2 and PGF2alpha, in each uterine cancer cell line expressing detectable levels of COX-1 and/or COX-2 in presence of resveratrol. Although COX expression was identified as a target of resveratrol in uterine cancer cells, inhibition of COX activity or exogenously added PGE2 did not modulate the effect of resveratrol on cellular proliferation.


CONCLUSIONS
High-dose of resveratrol exerts tumoricidal activity over uterine cancer cells and regulates COX expression. In these cells, resveratrol would not directly target COX activity, but possibly other enzymes involved in prostaglandin synthesis that act downstream of the COXs.
Sexton
Emilie
E
Département de Chimie-Biologie, Groupe de Recherche en Biopathologies Cellulaires et Moléculaires, Université du Québec à Trois-Rivières, C.P. 500, Trois-Rivières, Québec, G9A 5H7, Canada. emilie.sexton@uqtr.ca
Van Themsche
Céline
C
LeBlanc
Kim
K
Parent
Sophie
S
Lemoine
Pascal
P
Asselin
Eric
E
D017209:Apoptosis / Q000187:drug effects*; D002277:Carcinoma / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology; D016889:Endometrial Neoplasms / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*; D014594:Uterine Neoplasms / Q000378:metabolism*
D013267:Stilbenes; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D051057:Proto-Oncogene Proteins c-akt; D015232:Dinoprostone; D000077185:Resveratrol