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首页> 外文期刊>Life sciences >Gamma- and delta-tocotrienols exert a more potent anticancer effect than alpha-tocopheryl succinate on breast cancer cell lines irrespective of HER-2eu expression.
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Gamma- and delta-tocotrienols exert a more potent anticancer effect than alpha-tocopheryl succinate on breast cancer cell lines irrespective of HER-2eu expression.

机译：与HER-2 / neu表达无关，γ-和δ-生育三烯酚对乳腺癌细胞系的作用比α-生育酚琥珀酸酯更有效。

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AIMS: Breast cancer is the most common malignancy among women, with an age-specific incidence profile. During the last years much evidence has accumulated demonstrating the anticancer activity of tocotrienols (T3), a subfamily of natural vitamin E (VE). In this study, mouse and human breast cancer cells (with or without HER-2eu oncogene overexpression) were used to investigate the anticancer effect of alpha-, gamma-, and delta-tocotrienols in comparison with alpha-tocopheryl succinate (alpha-TOS), a synthetic derivative with widely recognized anticancer properties. MAIN METHODS: Human and mouse breast cancer cell lines were used. The effect of VE compounds on cell viability was investigated using Alamar Blue assay. Apoptosis was assessed by propidium iodide and JC-1 staining. Expression of senescence-associated markers was evaluated by RT-PCR and Western blot analysis was used to examine the changes in the expression levels of HER-2eu. KEY FINDINGS: gamma- and delta-Tau3 reduced cell viability with IC(50) values of less than half those of alpha-T3 and alpha-TOS. gamma- and delta-Tau3, and alpha-TOS to a lesser extent, induced apoptosis possibly via the mitochondrial pathway, and the expression of senescent-like growth arrest markers as p53, p21, and p16. Both alpha-TOS and tocotrienols downregulated HER-2eu in tumor cells overexpressing this oncogene, but this effect did not seem to be essential for the antitumor activity of these compounds. SIGNIFICANCE: We demonstrate that in HER-2eu breast cancer cells, the non-alpha form of T3 shows stronger anticancer activity than the synthetic VE-derivative alpha-TOS and this effect occurs independently from the inhibition of HER-2eu oncogene expression.
机译：目的：乳腺癌是女性中最常见的恶性肿瘤，具有特定年龄的发病率。在过去的几年中，已经积累了许多证据，证明天然维生素E（VE）的一个子家族生育三烯酚（T3）的抗癌活性。在这项研究中，小鼠和人类乳腺癌细胞（有或没有HER-2 / neu癌基因过表达）用于研究α-，γ-和δ-生育三烯酚与α-生育酚琥珀酸酯（α- TOS），一种具有广泛公认的抗癌特性的合成衍生物。主要方法：使用人和小鼠乳腺癌细胞系。使用Alamar Blue分析法研究了VE化合物对细胞活力的影响。通过碘化丙啶和JC-1染色评估细胞凋亡。通过RT-PCR评估衰老相关标志物的表达，并使用蛋白质印迹分析来检查HER-2 / neu的表达水平的变化。主要发现：γ-Tau3和δ-Tau3降低了细胞活力，IC（50）值不到α-T3和α-TOS的一半。 γ-和δ-Tau3，以及α-TOS在较小程度上诱导了细胞凋亡，可能是通过线粒体途径，以及衰老样生长停滞标记物p53，p21和p16的表达。在过量表达该癌基因的肿瘤细胞中，α-TOS和生育三烯酚均下调HER-2 / neu，但是对于这些化合物的抗肿瘤活性而言，这种作用似乎并不是必需的。意义：我们证明，在HER-2 / neu乳腺癌细胞中，T3的非α形式显示出比合成VE衍生物α-TOS更强的抗癌活性，并且这种作用独立于HER-2 / neu癌基因的抑制而发生表达。

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