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白藜芦醇可逆转肿瘤启动子诱导的间隙连接细胞间通讯抑制。

Resveratrol reverses tumor-promoter-induced inhibition of gap-junctional intercellular communication.

作者信息

Nielsen M, Ruch R J, Vang O

机构信息

Department of Chemistry and Life Sciences, Roskilde University, Roskilde, DK-4000, Denmark.

出版信息

Biochem Biophys Res Commun. 2000 Sep 7;275(3):804-9. doi: 10.1006/bbrc.2000.3378.

DOI:10.1006/bbrc.2000.3378
PMID:10973802
Abstract

The naturally occurring stilbene/alexin trans-resveratrol (trans-3,5, 4'-trihydroxystilbene) is a promising agent for the prevention of cancer. We investigated the effect of resveratrol on gap-junctional intercellular communication (GJIC) in WB-F344 rat liver epithelial cells because inhibition of GJIC is an important mechanism of tumor promotion. Seventeen to 50 microM resveratrol increased GJIC significantly by a factor of 1.3 compared with solvent vehicle controls, when the WB-F344 cells were exposed to resveratrol for 6 h. Most tumor promoters, including the phorbol ester TPA and the insecticide DDT, block GJIC. Resveratrol at 17-50 microM also significantly prevented down-regulation of GJIC by TPA and DDT, by a factor of 2.7 and 1.8, respectively. This recovery of GJIC from TPA inhibition was partly correlated with hindered hyperphosphorylation of Cx43. In conclusion, resveratrol was found to enhance GJIC and counteract the effects of tumor promoters on GJIC, and this is likely a mechanism that contributes to the antipromotional and anticarcinogenic properties of resveratrol.

摘要

天然存在的芪类/防御素反式白藜芦醇(反式-3,5,4'-三羟基芪)是一种很有前景的癌症预防剂。我们研究了白藜芦醇对WB-F344大鼠肝上皮细胞间隙连接细胞间通讯(GJIC)的影响,因为抑制GJIC是肿瘤促进的一个重要机制。当WB-F344细胞暴露于白藜芦醇6小时后,17至50微摩尔的白藜芦醇使GJIC显著增加,与溶剂载体对照组相比增加了1.3倍。大多数肿瘤促进剂,包括佛波酯TPA和杀虫剂滴滴涕,都会阻断GJIC。17至50微摩尔的白藜芦醇还分别以2.7倍和1.8倍的倍数显著阻止了TPA和滴滴涕对GJIC的下调作用。从TPA抑制中恢复GJIC部分与Cx43的过度磷酸化受阻相关。总之,发现白藜芦醇可增强GJIC并抵消肿瘤促进剂对GJIC的影响,这可能是一种有助于白藜芦醇抗促进和抗癌特性的机制。

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