tailieunhanh - Báo cáo khoa học: " The ATM and ATR inhibitors CGK733 and caffeine suppress cyclin D1 levels and inhibit cell proliferation"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Radiation Oncology cung cấp cho các bạn kiến thức về ngành y đề tài: " The ATM and ATR inhibitors CGK733 and caffeine suppress cyclin D1 levels and inhibit cell proliferation. | Radiation Oncology BioMed Central Open Access Short report The ATM and ATR inhibitors CGK733 and caffeine suppress cyclin D1 levels and inhibit cell proliferation John P Alao and Per Sunnerhagen Address Department of Cell and Molecular Biology Lundberg Laboratory University of Gothenburg . Box 462 S-405 30 Gõteborg Sweden Email John P Alao - Per Sunnerhagen - Corresponding author Published 10 November 2009 Received 25 August 2009 Accepted 10 November 2009 Radiation Oncology 2009 4 51 doi l748-7l 7X-4-5I This article is available from http content 4 l 5l 2009 Alao and Sunnerhagen licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License http licenses by which permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited. Abstract The ataxia telangiectasia mutated ATM and the ATM- related ATR kinases play a central role in facilitating the resistance of cancer cells to genotoxic treatment regimens. The components of the ATM and ATR regulated signaling pathways thus provide attractive pharmacological targets since their inhibition enhances cellular sensitivity to chemo- and radiotherapy. Caffeine as well as more specific inhibitors of ATM KU55933 or ATM and ATR CGK733 have recently been shown to induce cell death in drug-induced senescent tumor cells. Addition of these agents to cancer cells previously rendered senescent by exposure to genotoxins suppressed the ATM mediated p2l expression required for the survival of these cells. The precise molecular pharmacology of these agents however is not well characterized. Herein we report that caffeine CGK733 and to a lesser extent KU55933 inhibit the proliferation of otherwise untreated human cancer and nontransformed mouse fibroblast cell lines. Exposure of human cancer cell lines to caffeine and .