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標題: Oxidized beta-carotene inhibits gap junction intercellular communication in the human lung adenocarcinoma cell line A549
作者: Yeh, S.L.
Hu, M.L.
關鍵字: beta-carotene;oxidative degradation;gap junction intercellular;communication;connexin;biological-activities;dietary carotenoids;epithelial-cells;cigarette-smoke;gene-expression;cancer;connexin43;liver;rat;ferrets
Project: Food and Chemical Toxicology
期刊/報告no:: Food and Chemical Toxicology, Volume 41, Issue 12, Page(s) 1677-1684.
in addition to its antioxidant activity, beta-carotene (BC) is known to enhance gap junction intercellular communication (GJIC) by up-regulation of connexin 43 (Cx43), an action that may be important in its control of tumor growth. Surprisingly, two clinical trials on supplemental BC suggest that BC may increase lung cancer incidence in smokers. Recently, an animal study indicated that a very high dose of BC (50 mg/kg b.w./day for 5 days) decreases GJIC in rat liver, while a lower dose (5 mg/kg b.w./day) increases GJIC. It is unclear how high-doses of BC inhibit GJIC. In this study, we tested whether oxidized BC (OBC, obtained by heating BC at 60degreesC in open air for 1 h) may inhibit GJIC. We incubated a human lung cancer cell line (A549) with OBC or BC at 2-10 muM for 5 days. Cell viability (by Trypan-blue assay), GJIC (by scrape-loading dye transfer) and Cx43 expression (by western blotting and immunocytochemical localization) were measured to investigate the effects of OBC and BC on GJIC and the possible mechanisms. The results show that OBC at concentrations lower than 10 muM did not significantly affect cell viability. However, OBC at 5 muM inhibited GJIC, whereas BC at 5 muM markedly increased GJIC. The loss of GJIC in A549 induced by OBC accompanied the aberrant localization and phosphorylation of connexin43 (Cx43). These changes in the expression of Cx43 induced by OBC were similar to those induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), a tumor promoter. Thus, our results suggest that in vivo inhibition of GJIC by a high dose of BC on GJIC is, at least in part, attributable to the effect of OBC. (C) 2003 Elsevier Ltd. All rights reserved.
ISSN: 0278-6915
DOI: 10.1016/s0278-6915(03)00192-3
Appears in Collections:食品暨應用生物科技學系

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