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Anti-tumor Properties of cis-Resveratrol Methylated Analogues in Metastatic Mouse Melanoma Cells

机译:顺式白藜芦醇甲基化类似物在转移性小鼠黑素瘤细胞中的抗肿瘤特性

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摘要

Resveratrol (E-3,5,4’-trihydroxystilbene) is a polyphenol found in red wine that has been shown to have multiple anti-cancer properties. Although cis (Z) and trans (E) isomers of resveratrol occur in nature, the cis form is not biologically active. However, methylation at key positions of the cis form results in more potent anti-cancer properties. This study determined that synthetic cis-polymethoxystilbenes (methylated analogues of cis-resveratrol) inhibited cancer-related phenotypes of metastatic B16 F10 and non-metastatic B16 F1 mouse melanoma cells. In contrast with cis or trans-resveratrol and trans-polymethoxystilbene which were ineffective at 10 μM, cis-polymethoxystilbenes inhibited motility and proliferation of melanoma cells with low micromolar specificity (IC50 <10 μM). Inhibitory effects by cis-polymethoxystilbenes were significantly stronger with B16 F10 cells and were accompanied by decreased expression of β-tubulin and pleckstrin homology domain-interacting protein, a marker of metastatic B16 cells. Thus, cis-polymethoxystilbenes have potential as chemotherapeutic agents for metastatic melanoma.
机译:白藜芦醇(E-3,5,4'-三羟基sti)是一种在红酒中发现的多酚,具有多种抗癌特性。尽管白藜芦醇的顺式(Z)和反式(E)异构体在自然界存在,但顺式形式没有生物活性。然而,在顺式形式的关键位置处的甲基化导致更有效的抗癌特性。这项研究确定了合成的顺式-聚甲氧基对苯二酚(顺式白藜芦醇的甲基化类似物)抑制了与癌症相关的转移性B16 F10和非转移性B16 F1小鼠黑素瘤细胞表型。与在10μM下无效的顺式或反式白藜芦醇和反式聚甲氧基苯乙烯相反,顺式-聚甲氧基苯乙烯抑制了黑色素瘤细胞的运动性和增殖,且微摩尔特异性较低(IC50 <10μM)。在B16 F10细胞中,顺式-聚甲氧基对苯二酚的抑制作用明显增强,并伴有转移性B16细胞标志物β-微管蛋白和pleckstrin同源结构域相互作用蛋白的表达降低。因此,顺式-聚甲氧基芪具有作为转移性黑色素瘤的化学治疗剂的潜力。

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