Obatoclax, a pan-BCL-2 Inhibitor, targets Cyclin D1 for degradation to induce antiproliferation in human colorectal carcinoma cells

ASIA unversity > 資訊學院 > 生物資訊與醫學工程學系 > 期刊論文 > Item 310904400/102160

jsp.display-item.identifier=請使用永久網址來引用或連結此文件: http://asiair.asia.edu.tw/ir/handle/310904400/102160

题名:	Obatoclax, a pan-BCL-2 Inhibitor, targets Cyclin D1 for degradation to induce antiproliferation in human colorectal carcinoma cells
作者:	柯子鴻;Or, Chi-Hung R.;Chang, Yachu;Chang, Yachu;Li, Wei-Cheng;Lin, Wei-Cheng;Le, Wee-Chyan;Lee, Wee-Chyan;Su, Hong-Lin;Su, Hong-Lin;Che, Muk-Wing;Cheung, Muk-Wing;Hua, Chang-Po;Huang, Chang-Po;Ho, Cheesang;Ho, Cheesang;張嘉哲;Chang, Chia-Che;*
贡献者:	生物科技學系
日期:	2017-01
上传时间:	2017-03-01 06:06:35 (UTC+0)
摘要:	Colorectal cancer is the third most common cancer worldwide. Aberrant overexpression of antiapoptotic BCL-2 (B-cell lymphoma 2) family proteins is closely linked to tumorigenesis and poor prognosis in colorectal cancer. Obatoclax is an inhibitor targeting all antiapoptotic BCL-2 proteins. A previous study has described the antiproliferative action of obatoclax in one human colorectal cancer cell line without elucidating the underlying mechanisms. We herein reported that, in a panel of human colorectal cancer cell lines, obatoclax inhibits cell proliferation, suppresses clonogenicity, and induces G1-phase cell cycle arrest, along with cyclin D1 downregulation. Notably, ectopic cyclin D1 overexpression abrogated clonogenicity suppression but also G1-phase arrest elicited by obatoclax. Mechanistically, pre-treatment with the proteasome inhibitor MG-132 restored cyclin D1 levels in all obatoclax-treated cell lines. Cycloheximide chase analyses further revealed an evident reduction in the half-life of cyclin D1 protein by obatoclax, confirming that obatoclax downregulates cyclin D1 through induction of cyclin D1 proteasomal degradation. Lastly, threonine 286 phosphorylation of cyclin D1, which is essential for initiating cyclin D1 proteasomal degradation, was induced by obatoclax in one cell line but not others. Collectively, we reveal a novel anticancer mechanism of obatoclax by validating that obatoclax targets cyclin D1 for proteasomal degradation to downregulate cyclin D1 for inducing antiproliferation.
關聯:	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
显示于类别:	[生物資訊與醫學工程學系 ] 期刊論文

文件中的档案:

档案	大小	格式	浏览次数
index.html	0Kb	HTML	483	检视/开启

在ASIAIR中所有的数据项都受到原著作权保护.

数据加载中.....