Experimental studies have shown that beta-carotene inhibited the growth of colon cancer cells, and human trials have demonstrated that the carotenoid reduces colon cell proliferation of adenomatous polyps; however, molecular mechanisms underlying this chemopreventive activity remain unclear. Because COX-2 has been implicated as a causative factor in colon carcinogenesis, the present study was designed to investigate the relation between the growth-inhibitory effect of the carotenoid and COX-2 expression in colon cancer cells. We evaluated the effects of beta-carotene on the growth of human colon adenocarcinoma cells overexpressing (LS-174, HT-29, WiDr) or not expressing (HCT116) COX-2. We also studied COX-2 expression induced by heregulin-alpha, apoptosis induction, reactive oxygen species (ROS) production, and extracellular signal-regulated kinase 1/2 (ERK1/2) activation. beta-Carotene (0.5-2.0 mumol/L) decreased COX-2 expression (P < 0.05) and prostaglandin E(2) (PGE(2)) production (P < 0.05) in colon cancer cells. This effect was not observed in cells treated with retinoic acid or retinol. The downregulation of COX-2 by the carotenoid occurred in both untreated and heregulin-treated cells. It was accompanied by an increased ability of cells to undergo apoptosis and by a decrease in intracellular ROS production and in the activation of ERK1/2. Moreover, cells not expressing COX-2 were insensitive to the growth-inhibitory and proapoptotic effects of the carotenoid. Here, we report that the suppression of COX-2 by beta-carotene may represent a molecular mechanism by which this compound acts as an antitumor agent in colon carcinogenesis.

Palozza, P., Serini, S., Maggiano, N. G., Tringali, G., Navarra, P., Ranelletti, F. O., Calviello, G., beta-Carotene Downregulates the Steady-State and Heregulin-{alpha}-Induced COX-2 Pathways in Colon Cancer Cells., <<JOURNAL OF NUTRITION>>, 2005; (135): 129-136 [http://hdl.handle.net/10807/23100]

beta-Carotene Downregulates the Steady-State and Heregulin-{alpha}-Induced COX-2 Pathways in Colon Cancer Cells.

Palozza, Paola;Serini, Simona;Maggiano, Nicola Giuseppe;Tringali, Giuseppe;Navarra, Pierluigi;Ranelletti, Franco Oreste;Calviello, Gabriella
2005

Abstract

Experimental studies have shown that beta-carotene inhibited the growth of colon cancer cells, and human trials have demonstrated that the carotenoid reduces colon cell proliferation of adenomatous polyps; however, molecular mechanisms underlying this chemopreventive activity remain unclear. Because COX-2 has been implicated as a causative factor in colon carcinogenesis, the present study was designed to investigate the relation between the growth-inhibitory effect of the carotenoid and COX-2 expression in colon cancer cells. We evaluated the effects of beta-carotene on the growth of human colon adenocarcinoma cells overexpressing (LS-174, HT-29, WiDr) or not expressing (HCT116) COX-2. We also studied COX-2 expression induced by heregulin-alpha, apoptosis induction, reactive oxygen species (ROS) production, and extracellular signal-regulated kinase 1/2 (ERK1/2) activation. beta-Carotene (0.5-2.0 mumol/L) decreased COX-2 expression (P < 0.05) and prostaglandin E(2) (PGE(2)) production (P < 0.05) in colon cancer cells. This effect was not observed in cells treated with retinoic acid or retinol. The downregulation of COX-2 by the carotenoid occurred in both untreated and heregulin-treated cells. It was accompanied by an increased ability of cells to undergo apoptosis and by a decrease in intracellular ROS production and in the activation of ERK1/2. Moreover, cells not expressing COX-2 were insensitive to the growth-inhibitory and proapoptotic effects of the carotenoid. Here, we report that the suppression of COX-2 by beta-carotene may represent a molecular mechanism by which this compound acts as an antitumor agent in colon carcinogenesis.
Inglese
Palozza, P., Serini, S., Maggiano, N. G., Tringali, G., Navarra, P., Ranelletti, F. O., Calviello, G., beta-Carotene Downregulates the Steady-State and Heregulin-{alpha}-Induced COX-2 Pathways in Colon Cancer Cells., <<JOURNAL OF NUTRITION>>, 2005; (135): 129-136 [http://hdl.handle.net/10807/23100]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/23100
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