Peroxisome Proliferator-Activated Receptor γ (PPAR-γ) Agonist Rosiglitazone (RGZ) Inhibits HL-60 Cell Growth by Induction of Apoptosis

Objective To investigate the apoptotic effects of peroxisome proliferator-activated receptor γ (PPAR-γ) agonist rosiglitazone (RGZ) on leukemia HL-60 cells. Methods Cell apoptosis was measured by flow cytometry, Hoechst 33258 staining, and DNA fragmentation assay. The expression of caspase-3 and apoptosis-related gene Bax and Bcl-2 as well as survivin expression were analyzed by Western blotting. Results Rosiglitazone (over 40 μmol/L) could inhibit the growth of HL-60 cells and substantially cause apoptosis. Apoptotic cells were observed clearly by Hoechst staining, especially after the cells were treated with RGZ for 72 h, and a DNA fragmentation assay showed a typical DNA ladder. Western blotting showed cleavage of the caspase-3 zymogen protein (32-kD) with the appearance of its 17-kD cleavage and down-regulation of anti-apoptotic protein Bcl-2 and survivin as well as up-regulaton of pro-apoptotic protein Bax . Conclusion Rosiglitazone can inhibit HL-60 cell growth by the induction of apoptosis. Activation of caspase-3 and down-regulation of Bcl-2 and survivin as well as up-regulation of Bax expression may be one of its most important mechanisms.