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沙棘原花青素对脂肪酸合酶及MDA-MB-231细胞的抑制作用。

Inhibitory effects of sea buckthorn procyanidins on fatty acid synthase and MDA-MB-231 cells.

作者信息

Wang Yi, Nie Fangyuan, Ouyang Jian, Wang Xiaoyan, Ma Xiaofeng

机构信息

College of Life Sciences, University of Chinese Academy of Sciences, No. 19A Yuquan Road, 100049, Beijing, China.

出版信息

Tumour Biol. 2014 Oct;35(10):9563-9. doi: 10.1007/s13277-014-2233-1. Epub 2014 Jun 24.

Abstract

Fatty acid synthase (FAS) is overexpressed in many human cancers including breast cancer and is considered to be a promising target for therapy. Sea buckthorn has long been used to treat a variety of maladies. Here, we investigated the inhibitory effect of sea buckthorn procyanidins (SBPs) isolated from the seeds of sea buckthorn on FAS and FAS overexpressed human breast cancer MDA-MB-231 cells. The FAS activity and FAS inhibition were measured by a spectrophotometer at 340 nm of nicotinamide adenine dinucleotide phosphate (NADPH) absorption. We found that SBP potently inhibited the activity of FAS with a half-inhibitory concentration (IC50) value of 0.087 μg/ml. 3-4,5-Dimethylthiazol-2-yl-2,3-diphenyl tetrazolium bromide (MTT) assay was used to test the cell viability. SBP reduced MDA-MB-231 cell viability with an IC50 value of 37.5 μg/ml. Hoechst 33258/propidium iodide dual staining and flow cytometric analysis showed that SBP induced MDA-MB-231 cell apoptosis. SBP inhibited intracellular FAS activity with a dose-dependent manner. In addition, sodium palmitate could rescue the cell apoptosis induced by SBP. These results showed that SBP was a promising FAS inhibitor which could induce the apoptosis of MDA-MB-231 cells via inhibiting FAS. These findings suggested that SBP might be useful for preventing or treating breast cancer.

摘要

脂肪酸合酶(FAS)在包括乳腺癌在内的多种人类癌症中过表达,被认为是一个有前景的治疗靶点。沙棘长期以来被用于治疗各种疾病。在此,我们研究了从沙棘种子中分离出的沙棘原花青素(SBPs)对FAS以及FAS过表达的人乳腺癌MDA-MB-231细胞的抑制作用。通过分光光度计在340nm处测定烟酰胺腺嘌呤二核苷酸磷酸(NADPH)的吸光度来测量FAS活性和FAS抑制率。我们发现SBP能有效抑制FAS的活性,半数抑制浓度(IC50)值为0.087μg/ml。采用3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐(MTT)法检测细胞活力。SBP降低MDA-MB-231细胞活力,IC50值为37.5μg/ml。Hoechst 33258/碘化丙啶双重染色和流式细胞术分析表明SBP诱导MDA-MB-231细胞凋亡。SBP以剂量依赖的方式抑制细胞内FAS活性。此外,棕榈酸钠可以挽救SBP诱导的细胞凋亡。这些结果表明SBP是一种有前景的FAS抑制剂,它可以通过抑制FAS诱导MDA-MB-231细胞凋亡。这些发现提示SBP可能对预防或治疗乳腺癌有用。

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