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Titolo:
HMG-CoA reductase inhibitor mevastatin enhances the growth inhibitory effect of butyrate in the colorectal carcinoma cell line Caco-2
Autore:
Wachtershauser, A; Akoglu, B; Stein, J;
Indirizzi:
Univ Frankfurt, Dept Med 2, D-60590 Frankfurt, Germany Univ Frankfurt Frankfurt Germany D-60590 d 2, D-60590 Frankfurt, Germany
Titolo Testata:
CARCINOGENESIS
fascicolo: 7, volume: 22, anno: 2001,
pagine: 1061 - 1067
SICI:
0143-3334(200107)22:7<1061:HRIMET>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
LOVASTATIN INDUCES APOPTOSIS; COLONIC EPITHELIAL-CELLS; CANCER-CELLS; SODIUM-BUTYRATE; FAMILIAL HYPERCHOLESTEROLEMIA; MEVALONATE PATHWAY; CYCLE ARREST; EXPRESSION; DIFFERENTIATION; CHOLESTEROL;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
57
Recensione:
Indirizzi per estratti:
Indirizzo: Stein, J Univ Frankfurt, Dept Med 2, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany Univ Frankfurt Theodor-Stern-Kai 7 Frankfurt Germany D-60590 any
Citazione:
A. Wachtershauser et al., "HMG-CoA reductase inhibitor mevastatin enhances the growth inhibitory effect of butyrate in the colorectal carcinoma cell line Caco-2", CARCINOGENE, 22(7), 2001, pp. 1061-1067

Abstract

Mevastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol synthesis, Butyrate,a short-chain fatty acid, reduces proliferation and induces differentiation of human colon cancer cells. The aim of our study was to determine the effect of mevastatin, alone or in combination with butyrate, on proliferation, the cell cycle and apoptosis in the human colorectal carcinoma cell line Caco-2, In this report we show that mevastatin combined with butyrate synergistically suppressed growth of Caco-2 cells in a dose-and time-dependent manner. In addition, incubation with mevastatin arrested cells in the G(1) phase of the cell cycle after 24 h with a switch to the G(2)/M phase after 72 h, This was accompanied by a down-regulation of cyclin-dependent kinases (cdk) 4 and cdk 6 as well as cyclin DI, while cdk 2 and cyclin E protein levels remained unchanged during mevastatin treatment. Cell cycle inhibitors p21 and p27 were significantly upregulated by mevastatin. The proapoptotic properties of mevastatin were further enhanced by co-incubation with butyrate, Lastly, the effects of mevastatin could be reversed by addition of mevalonate, but not farnesyl- or geranylgeranylpyrophosphate, intermediate products of cholesterol synthesis, to the medium. These results suggest that HMG-CoA reductase inhibitors like mevastatin may enhance the antiproliferative effect of butyrate in colon cancer cells via induction of apoptosis together with a G(0)/G(1) cell cycle arrest.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/05/20 alle ore 14:58:43