Effects of peptidic antagonists of Grb2-SH2 on human breast cancer cells

Tunghai University Institutional Repository > 理學院 > 化學系所 > 期刊論文 > Item 310901/21302

jsp.display-item.identifier=請使用永久網址來引用或連結此文件: http://140.128.103.80:8080/handle/310901/21302

题名:	Effects of peptidic antagonists of Grb2-SH2 on human breast cancer cells
作者:	Chen, C.-H., Chen, M.-K., Jeng, K.-C.G., Lung, F.-D.T.
贡献者:	Department of Chemistry, Tunghai University
关键词:	Apoptosis;Cell cycle;Cell viability;Cytotoxicity;Human breast cancer cell line;Peptide
日期:	2010
上传时间:	2013-05-14T09:04:41Z (UTC)
摘要:	The growth factor receptor-bound protein Src homology 2 (Grb2-SH2) plays an important role in the oncogenic Ras signaling pathway, which involves in cell proliferation and differentiation. Therefore, the antagonist of Grb2-SH2 has become a potential target for developing anticancer agents. Recently, we discovered the peptide 1 (Fmoc-Glu-Tyr-Aib-Asn-NH 2) with high affinity for the Grb2-SH2 domain by using surface plasmon resonance (SPR)-biosensor technology. Herein, we report the further design of the lead peptide 1 by addition of an Arg-Gly-Asp sequence to 1 to enhance its binding to Grb2-SH2 and to induce apoptosis in cancer cells. Both the linear and cyclic analogs of the newly designed compounds were prepared along with an analog in which the N α -Fmoc group was removed. These peptide analogs were assayed for their affinity for the Grb2-SH2, their antiproliferative effect on human breast cancer cells, their specificity for cancer cells, and their effects on cytotoxicity and the cell cycle. MCF-7 and MDA-MB-453 breast cancer cells were treated with various concentrations of each peptide. The cell viability and cytotoxicity of peptide-treated cells were determined by using the cell proliferation kit (3-[4, 5-dimethyl-2-thiazolyl]-2, 5-diphenyl-tetrazolium bromide, MTT) and cytotoxicity kit (lactate dehydrogenase, LDH), respectively. Effects of peptides on the cell cycle progression of cancer cells and apoptosis were analyzed by using flow cytometry. Results demonstrated that the peptide analog 2 (H-Arg-Gly-AspGlu-Tyr-Aib-Asn-Arg-Gly-Asp-NH 2) had anti-proliferative effects on MCF-7 and MDA-MB-453 cells with the IC 50 of 45.7 μM and 47.4 μM, respectively. The cytotoxicity and percentage of sub-G1 in the cell cycle were increased in these cancer cells when cells were treated with higher concentration of the Arg-Gly-Asp-containing peptide 2. These results provide important information for the development of anti-cancer agents. ? 2010 Bentham Science Publishers Ltd.
關聯:	Protein and Peptide Letters 17 (1) , pp. 44-53
显示于类别:	[化學系所] 期刊論文

文件中的档案:

档案	大小	格式	浏览次数
index.html	0Kb	HTML	122	检视/开启

在THUIR中所有的数据项都受到原著作权保护.

数据加载中.....