Chaumontet C, Bex V, Gaillard-Sanchez I, Seillan-Heberden C, Suschetet M, Martel P
Laboratoire de Nutrition et Sécurité Alimentaire, INRA, Jouy-en-Josas, France.
Carcinogenesis. 1994 Oct;15(10):2325-30. doi: 10.1093/carcin/15.10.2325.
Two flavones, apigenin and tangeretin, were studied for their ability to modulate gap junctional intercellular communication (GJIC) in the rat liver epithelial cell line REL. Their cytotoxicity was first determined by cell density and neutral red uptake assays: neither apigenin nor tangeretin are cytotoxic at 10 and 25 microM, the concentrations used in our experiments. We then studied GJIC using the dye transfer assay and we observed that both apigenin and tangeretin enhance it, the maximum stimulation (x 1.7-1.8) being achieved at 25 microM for 24 h. When the dye transfer was enhanced, the amount of connexin 43 increased, which was demonstrated by Western blot and immunofluorescence analysis. For apigenin only, Northern blot analysis showed an accumulation of connexin 43 mRNA. In addition, the incubation of REL cells with the two compounds, for 1 or 24 h, prevented the inhibition of dye transfer by 12-O-tetradecanoylphorbol-13-acetate (1 or 10 ng/ml). The enhancement of GJIC by apigenin could be one of the major mechanisms responsible for apigenin's anti-tumour promoting action in vivo. As for tangeretin, its capacity to enhance GJIC completes its potential protective properties towards the post-initiation process.
研究了两种黄酮类化合物芹菜素和陈皮素对大鼠肝上皮细胞系REL中缝隙连接细胞间通讯（GJIC）的调节能力。首先通过细胞密度和中性红摄取试验确定它们的细胞毒性：在我们实验中使用的10和25 microM浓度下，芹菜素和陈皮素均无细胞毒性。然后我们使用染料转移试验研究GJIC，观察到芹菜素和陈皮素均能增强GJIC，在25 microM处理24小时时达到最大刺激（增至1.7 - 1.8倍）。当染料转移增强时，通过蛋白质印迹和免疫荧光分析证实连接蛋白43的量增加。仅对于芹菜素，Northern印迹分析显示连接蛋白43 mRNA的积累。此外，将REL细胞与这两种化合物孵育1或24小时，可防止12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（1或10 ng/ml）对染料转移的抑制作用。芹菜素增强GJIC可能是其在体内抗肿瘤促进作用的主要机制之一。至于陈皮素，其增强GJIC的能力完善了其对启动后过程的潜在保护特性。
