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首页> 外文期刊>Biochemistry >Enhancement of Nitric Oxide and Superoxide Generations by alpha-Tocopheryl Succinate and Its Apoptotic and Anticancer Effects
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Enhancement of Nitric Oxide and Superoxide Generations by alpha-Tocopheryl Succinate and Its Apoptotic and Anticancer Effects

机译：琥珀酸α-生育酚酯增强一氧化氮和超氧化物的产生及其凋亡和抗癌作用

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摘要

Tocopheryl succinate (TS), a succinyl ester of alpha-tocopherol (alpha-T), has been reported to have various biological activities. In this communication, we review the current findings about TS including our recent studies of its effects on nitric oxide (NO) and superoxide (O_2) generations implicated in cancer and atherosclerosis. First, we investigated the effect of TS on NO production in vascular smooth muscle cells (VSMC) under atherosclerosis-like conditions using lipopolysaccharide (LPS) and interferon-gamma (IFN). TS enhanced LPS/IFN-dependent NO production, but alpha-T itself did not. The enhancement by TS of NO production was inhibited by alpha-T but not by antioxidants such as ascorbic acid and 2[3]-t-butyl-4-hydroxy-anisole (BHA). TS enhanced the amount of protein kinase Calpha (PKCalpha) in VSMC, and PKC inhibitors inhibited TS-enhanced NO production, suggesting that the enhancing effect of TS on NO production is caused by up-regulation of PKC. Second, we found that TS induced apoptosis in VSMC associated with increase in O_2~- generation via NADPH-dependent oxidase. We further observed that a mouse breast cancer cell line C127I was more susceptible for TS-induced apoptosis than a mouse breast normal cell line NmuMG, and that superoxide dismutase, alpha-T, and BHA inhibited TS-caused morphological cell damage in C127I. From these results, O_2 itself and/or other reactive oxygen species are assumed to associate with TS-induced cell toxicity, and antioxidative defense systems are supposed to be lowered in cancer cells. Finally, we found that intravenous injection of TS vesicles completely inhibited the growth of melanoma cells B16-F1 inoculated on the back of hairless mice and enhanced their survival time.
机译：据报道，生育酚琥珀酸酯（TS）是一种α-生育酚的琥珀酸酯（α-T），具有多种生物活性。在本交流中，我们回顾了有关TS的最新发现，包括我们对其与一氧化氮（NO）和超氧化物（O_2）世代相关的癌症和动脉粥样硬化的影响的最新研究。首先，我们研究了脂多糖（LPS）和干扰素-γ（IFN）在动脉粥样硬化样情况下，TS对血管平滑肌细胞（VSMC）NO产生的影响。 TS增强了LPS / IFN依赖性的NO产生，但alpha-T本身没有。 TS产生的NO的增加被α-T抑制，但未被抗氧化剂如抗坏血酸和2 [3]-叔丁基-4-羟基-茴香醚（BHA）抑制。 TS增强了VSMC中蛋白激酶Calpha（PKCalpha）的量，而PKC抑制剂抑制了TS增强的NO产生，这表明TS对NO产生的增强作用是由PKC的上调引起的。其次，我们发现TS通过NADPH依赖性氧化酶诱导了VSMC细胞凋亡，并伴随着O_2〜-生成的增加。我们进一步观察到，小鼠乳腺癌细胞系C127I比小鼠乳腺癌正常细胞系NmuMG更易受TS诱导的凋亡的影响，并且超氧化物歧化酶，α-T和BHA抑制了TS引起的C127I形态细胞的损伤。根据这些结果，可以认为O_2本身和/或其他活性氧与TS诱导的细胞毒性有关，并且抗氧化防御系统在癌细胞中会降低。最后，我们发现静脉内注射TS囊泡完全抑制了接种在无毛小鼠背部的黑色素瘤细胞B16-F1的生长并延长了它们的存活时间。

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