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微生物脂肽对肿瘤细胞系的影响:通过干扰细胞膜脂肪酸组成诱导细胞凋亡。

Effect of the microbial lipopeptide on tumor cell lines: apoptosis induced by disturbing the fatty acid composition of cell membrane.

机构信息

State Key Laboratory of Bioreactor Engineering and Institute of Applied Chemistry, East China University of Science and Technology, Shanghai 200237, China.

出版信息

Protein Cell. 2010 Jun;1(6):584-94. doi: 10.1007/s13238-010-0072-4. Epub 2010 Jul 7.

Abstract

Microbial lipopeptides play an important role in apoptosis induction of tumor cells. However, there is little knowledge about the relationship between apoptosis induction and membrane fatty acids. The present study focused on the effects of lipopeptides produced by Bacillus subtilis HSO121 on Bcap-37 cell lines. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl (MTT) colorimetric assay and surface tension measurements, showed that the critical micelle concentration (CMC) was a critical level for the inhibitory activity of lipopeptides on the growth of Bcap-37 cells. Under the CMC, the order of least to greatest cytotoxicity effect on cancer cell lines by lipopeptides is C(13)-lipopeptide < C(14)-lipopepitde < C(15)-lipopeptide. Above CMC, all lipopeptides directly exert cytolytic activity. The flow cytometric analysis and Hoechst33258 staining experiments confirmed the apoptosis of Bcap-37 cell lines induced by lipopeptides in a dose-dependent manner. This apoptosis was associated with a significant decrease of the unsaturated degree of the cellular fatty acids of Bcap-37 cell lines due to the changes in the cellular fatty acids composition induced by the lipopeptide treatment. These results indicated that disturbance of the cellular fatty acid composition of breast cancer cell lines were related to in the cell apoptosis. Furthermore, significant difference in IC(50) values of tumor cells and normal cell showed that the lipopeptide exerted selective cytotoxicity on the cancer cells. Thus HSO121 lipopeptides may have potential applications as an anticancer leads.

摘要

微生物脂肽在诱导肿瘤细胞凋亡中发挥重要作用。然而,关于凋亡诱导与膜脂肪酸之间的关系知之甚少。本研究主要关注枯草芽孢杆菌 HSO121 产生的脂肽对 Bcap-37 细胞系的影响。3-(4,5-二甲基噻唑-2-基)-2,5-二苯基(MTT)比色法和表面张力测量结果表明,临界胶束浓度(CMC)是脂肽抑制 Bcap-37 细胞生长的活性的关键水平。在 CMC 下,脂肽对癌细胞系的最小至最大细胞毒性作用的顺序为 C(13)-脂肽 < C(14)-脂肽 < C(15)-脂肽。高于 CMC 时,所有脂肽均直接发挥细胞溶解活性。流式细胞术分析和 Hoechst33258 染色实验证实了脂肽诱导 Bcap-37 细胞系凋亡呈剂量依赖性。这种凋亡与 Bcap-37 细胞系的细胞脂肪酸不饱和程度显著降低有关,这是由于脂肽处理引起的细胞脂肪酸组成的变化。这些结果表明,乳腺癌细胞系的细胞脂肪酸组成的紊乱与细胞凋亡有关。此外,肿瘤细胞和正常细胞的 IC(50) 值存在显著差异,表明脂肽对癌细胞具有选择性细胞毒性。因此,HSO121 脂肽可能具有作为抗癌先导的潜力。

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