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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >Differential suppression of proliferation in MCF-7 and MDA-MB-231 breast cancer cells exposed to alpha-, gamma- and delta-tocotrienols is accompanied by altered expression of oxidative stress modulatory enzymes.
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Differential suppression of proliferation in MCF-7 and MDA-MB-231 breast cancer cells exposed to alpha-, gamma- and delta-tocotrienols is accompanied by altered expression of oxidative stress modulatory enzymes.

机译：在暴露于α-，γ-和δ-生育三烯酚的MCF-7和MDA-MB-231乳腺癌细胞中，增殖的差异性抑制伴随着氧化应激调节酶表达的改变。

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Tocotrienols belong to the vitamin E family of chemicals known to have potent anti-proliferative and apoptotic activities against a variety of cancer cells with little to no comparable influence on the normal cells. Whether tocotrienols control the expression of phase II antioxidant enzymes in the context of their anti-carcinogenic mechanisms has not been investigated. The present studies were performed to test whether the differential growth inhibition resulting from exposure to alpha-, gamma- and delta-tocotrienols in estrogen receptor-positive human MCF-7 and estrogen receptor-negative MDA-MB-231 breast cancer cells might be accompanied by changes in phase II antioxidant enzymes. Cell proliferation and clonogenicity in both cell lines were significantly inhibited by gamma- and delta-tocotrienols with little affect when cells were similarly exposed to alpha-tocotrienol, at doses up to 10 muM. The expression and activity of several antioxidant enzymes in 10 muM tocotrienol-treated cells were determined by Western blot and biochemical assays. In MDA-MB-231 cells, delta- was more active than alpha- or gamma-tocotrienols in up-regulating glutathione peroxidase; however, the three tocotrienols had comparable activity in inducing thioredoxin. In MCF-7 cells, expression of quinone reductase 2 and thioredoxin was increased by gamma- and delta-tocotrienols, whereas quinone reductase 1 was unaffected by exposure to the tocotrienols. The tocotrienols also did not affect the expression and activity of superoxide dismutase in both MCF-7 and MDA-MB-231 cells, but increased catalase activity concomitant with slight reduction in the catalase expression. In MDA-MB-231 cells, treatment by tocotrienols led to several fold increase of NRF2 expression marked by corresponding decrease in KEAP1 levels. By contrast, no significant change in NRF2 and KEAP1 levels was observed in MCF-7 cells. These studies demonstrate that different tocotrienols show distinct and selective activity in regulating the NRF2-KEAP1, in coordination with the induced expression of cytoprotective oxidative stress modulatory genes and regulation of proliferation in breast cancer cells.
机译：生育三烯酚属于维生素E家族的化学品，已知对多种癌细胞具有有效的抗增殖和凋亡活性，而对正常细胞的影响很小甚至没有可比性。尚未研究生育三烯酚是否在其抗癌机制中控制了II期抗氧化剂的表达。进行本研究以测试在雌激素受体阳性的人MCF-7和雌激素受体阴性的MDA-MB-231乳腺癌细胞中，由于暴露于α-，γ-和δ-生育三烯酚而导致的差异性生长抑制通过改变II期抗氧化酶。 γ-和δ-生育三烯酚可显着抑制两种细胞系中的细胞增殖和克隆形成性，当细胞以10μM的剂量相似地暴露于α-生育三烯酚时几乎没有影响。通过蛋白质印迹法和生化测定法确定了10μM生育三烯酚处理的细胞中几种抗氧化酶的表达和活性。在MDA-MB-231细胞中，在上调谷胱甘肽过氧化物酶方面，δ-比α-或γ-生育三烯酚更活跃。然而，三种生育三烯酚在诱导硫氧还蛋白方面具有可比的活性。在MCF-7细胞中，γ-和δ-生育三烯酚会增加醌还原酶2和硫氧还蛋白的表达，而醌还原酶1不会受到暴露于生育三烯酚的影响。生育三烯酚也不会影响MCF-7和MDA-MB-231细胞中超氧化物歧化酶的表达和活性，但会增加过氧化氢酶的活性，同时使过氧化氢酶的表达略有降低。在MDA-MB-231细胞中，生育三烯酚的处理导致NRF2表达增加数倍，其特征是KEAP1水平相应降低。相比之下，在MCF-7细胞中未观察到NRF2和KEAP1水平的显着变化。这些研究表明，不同的生育三烯酚在调节NRF2-KEAP1方面表现出独特的选择性活性，与细胞保护性氧化应激调节基因的诱导表达和乳腺癌细胞的增殖调节相协调。

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