title: Peroxisome proliferator-activated receptor-gamma agonist rosiglitazone--induced apoptosis in leukemia k562 cells and its mechanisms of action.
abstract: This study investigates the ability of a synthetic PPAR-gamma agonist, rosiglitazone (RGZ), to induce apoptosis in leukemia K562 cells. The results revealed that RGZ (>40 mmol/L) inhibits the growth of K562 cells and causes apoptosis in a time and dose-dependent manner. Apoptosis is observed clearly by Hoechst 33258 staining. Western blotting analysis demonstrates the cleavage of caspase-3 zymogen protein with the appearance of its 17-kD subunit and a dose-dependent cleavage of poly (ADP-ribose) polymerase. Furthermore, RGZ treatment down-regulates anti-apoptotic protein Bcl-2 and up-regulates pro-apoptotic protein Bax in a dosedependent manner after the cells are treated for 48 hours. Telomerase activity is decreased concurrently in a dosedependent manner. We therefore conclude that RGZ induces apoptosis in K562 cells in vitro, and that RGZ-induced apoptosis in K562 cells is highly correlated with activation of caspase-3, decreasing telomerase activity, down-regulation of the anti-apoptotic protein Bcl-2, and up-regulation of the pro-apoptotic protein Bax.
authors.affiliation: Department of Hematology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, P R China.
authors.forename: Jia-Jun
authors.initials: JJ
authors.lastname: Liu
authors.forename: Ting
authors.initials: T
authors.lastname: Hu
authors.forename: Xiang-Yuan
authors.initials: XY
authors.lastname: Wu
authors.forename: Chun-Zhi
authors.initials: CZ
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ruo-Zhi
authors.initials: RZ
authors.lastname: Xiao
authors.forename: Dong-Jun
authors.initials: DJ
authors.lastname: Lin
authors.forename: Ren-Wei
authors.initials: RW
authors.lastname: Huang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006690:Bisbenzimidazole / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D020014:K562 Cells; D047495:PPAR gamma / Q000819:agonists*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D000077154:Rosiglitazone; D019098:Telomerase / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000032:analysis
chemical_list: D000970:Antineoplastic Agents; C494826:BAX protein, human; D047495:PPAR gamma; D019253:Proto-Oncogene Proteins c-bcl-2; D045162:Thiazolidinediones; D051028:bcl-2-Associated X Protein; D000077154:Rosiglitazone; D019098:Telomerase; D053148:Caspase 3; D006690:Bisbenzimidazole