Mechanisms of action of nonpeptide hormones on resveratrol-induced antiproliferation of cancer cells.
Ann N Y Acad Sci
; 1403(1): 92-100, 2017 09.
Article
em En
| MEDLINE
| ID: mdl-28759712
ABSTRACT
Nonpeptide hormones, such as thyroid hormone, dihydrotestosterone, and estrogen, have been shown to stimulate cancer proliferation via different mechanisms. Aside from their cytosolic or membrane-bound receptors, there are receptors on integrin αv ß3 for nonpeptide hormones. Interaction between hormones and integrin αv ß3 can induce signal transduction and eventually stimulate cancer cell proliferation. Resveratrol induces inducible COX-2-dependent antiproliferation via integrin αv ß3 . Resveratrol and hormone-induced signals are both transduced by activated extracellular-regulated kinases 1 and 2 (ERK1/2); however, hormones promote cell proliferation, while resveratrol induces antiproliferation in cancer cells. Hormones inhibit resveratrol-stimulated phosphorylation of p53 on Ser15, resveratrol-induced nuclear COX-2 accumulation, and formation of p53-COX-2 nuclear complexes. Subsequently, hormones impair resveratrol-induced COX-2-/p53-dependent gene expression. The inhibitory effects of hormones on resveratrol action can be blocked by different antagonists of specific nonpeptide hormone receptors but not integrin αv ß3 blockers. Results suggest that nonpeptide hormones inhibit resveratrol-induced antiproliferation in cancer cells downstream of the interaction between ligand and receptor and ERK1/2 activation to interfere with nuclear COX-2 accumulation. Thus, the surface receptor sites for resveratrol and nonpeptide hormones are distinct and can induce discrete ERK1/2-dependent downstream antiproliferation biological activities. It also indicates the complex pathways by which antiproliferation is induced by resveratrol in various physiological hormonal environments. .
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Di-Hidrotestosterona
/
Estilbenos
/
Hormônios Tireóideos
/
Transdução de Sinais
/
Apoptose
/
Proliferação de Células
/
Estrogênios
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article