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通过线粒体和 MEK/ERK 介导的凋亡通路,萝卜硫素对人脑恶性神经胶质瘤 GBM8401 细胞生长抑制的影响。

Effect of sulforaphane on growth inhibition in human brain malignant glioma GBM 8401 cells by means of mitochondrial- and MEK/ERK-mediated apoptosis pathway.

机构信息

Department of Neurosurgery, Tainan Sin-Lau Hospital, Tainan, Taiwan.

出版信息

Cell Biochem Biophys. 2012 Jul;63(3):247-59. doi: 10.1007/s12013-012-9360-3.

Abstract

In recent studies, sulforaphane (SFN) has been seen to demonstrate antioxidant and anti-tumor activities as well as potent chemopreventive action against cancer. The present study investigates the anti-proliferation (using MTT assay, SFN demonstrated cytotoxic activity against GBM 8401 cell with IC(50) values at 35.52 μM) and induced apoptosis of SFN 24-h treatment in the cells of human brain malignant glioma GBM 8401 cells. We studied the MMP, caspase, MEK/ERK activation, and NF-κB transcription factor activity. Our results indicate that SFN inhibits cell proliferation as well as the activation of apoptosis in GBM 8401 cells. Both effects increased in proportion to the dosage of SFN, and apoptosis was induced via mitochondria- and caspase-dependent pathways. Daily s.c. injections of SFN for 3 weeks in severe combined immunodeficient mice (SCID) with GBM8401 s.c. tumors resulted in a decrease in mean tumor weight of 69-75 % compared with vehicle-treated controls. Our findings suggest that, in addition to the known effects on cancer prevention, SFN may provide antitumor activity in established malignant glioma.

摘要

在最近的研究中,发现萝卜硫素 (SFN) 具有抗氧化和抗肿瘤活性,以及对癌症的强大化学预防作用。本研究调查了 SFN 对人脑恶性神经胶质瘤 GBM 8401 细胞的抗增殖作用(通过 MTT 测定,SFN 对 GBM 8401 细胞表现出细胞毒性活性,IC50 值为 35.52 μM)和诱导凋亡作用,SFN 处理 24 小时。我们研究了 MMP、半胱天冬酶、MEK/ERK 激活和 NF-κB 转录因子活性。我们的结果表明,SFN 抑制 GBM 8401 细胞的增殖以及凋亡的激活。这两种作用都随 SFN 剂量的增加而增加,凋亡是通过线粒体和半胱天冬酶依赖性途径诱导的。SFN 每日 sc 注射 3 周,可使 sc 种植 GBM8401 肿瘤的严重联合免疫缺陷小鼠 (SCID) 中的肿瘤平均重量减少 69-75%,与对照组相比。我们的研究结果表明,除了对癌症预防的已知作用外,SFN 可能在已建立的恶性神经胶质瘤中具有抗肿瘤活性。

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