English  |  正體中文  |  简体中文  |  Items with full text/Total items : 90453/105672 (86%)
Visitors : 13087571      Online Users : 534
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
Scope Tips:
  • please add "double quotation mark" for query phrases to get precise results
  • please goto advance search for comprehansive author search
  • Adv. Search
    HomeLoginUploadHelpAboutAdminister Goto mobile version

    Please use this identifier to cite or link to this item: http://asiair.asia.edu.tw/ir/handle/310904400/102160

    Title: Obatoclax, a pan-BCL-2 Inhibitor, targets Cyclin D1 for degradation to induce antiproliferation in human colorectal carcinoma cells
    Authors: 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;*
    Contributors: 生物科技學系
    Date: 2017-01
    Issue Date: 2017-03-01 14:06:35 (UTC+8)
    Abstract: 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.
    Appears in Collections:[生物資訊與醫學工程學系 ] 期刊論文

    Files in This Item:

    File SizeFormat

    All items in ASIAIR are protected by copyright, with all rights reserved.

    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - Feedback