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targeting death receptor trail-r2 by chalcones for trail-induced apoptosis in cancer cells目标死亡受体trail-r2为trail-induced类化合物在肿瘤细胞凋亡.pdf

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targeting death receptor trail-r2 by chalcones for trail-induced apoptosis in cancer cells目标死亡受体trail-r2为trail-induced类化合物在肿瘤细胞凋亡

Int. J. Mol. Sci. 2012, 13, 15343-15359; doi:10.3390/ijms131115343 OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 /journal/ijms Article Targeting Death Receptor TRAIL-R2 by Chalcones for TRAIL-Induced Apoptosis in Cancer Cells Ewelina Szliszka †, Dagmara Jaworska †, Małgorzata Kłósek, Zenon P. Czuba and Wojciech Król * Chair and Department of Microbiology and Immunology, Medical University of Silesia in Katowice, Jordana 19, 41-808 Zabrze, Poland; E-Mails: eszliszka@.pl (E.S.); djaworska@.pl (D.J.); klosekmalgorzata@ (M.K.); zczuba@.pl (Z.P.C.) † These authors contributed equally to this work. * Author to whom correspondence should be addressed; E-Mail: wkrol@.pl; Tel./Fax: +48-322-722-554. Received: 24 October 2012; in revised form: 13 November 2012 / Accepted: 14 November 2012 / Published: 20 November 2012 Abstract: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in cancer cells without toxicity to normal cells. TRAIL binds to death receptors, TRAIL-R1 (DR4) and TRAIL-R2 (DR5) expressed on cancer cell surface and activates apoptotic pathways. Endogenous TRAIL plays an important role in immune surveillance and defense against cancer cells. However, as more tumor cells are reported to be resistant to TRAIL mediated death, it is important to search for and develop new strategies to overcome this resistance. Chalcones can sensitize