[Pro-apoptotic effect of ciglitazone in leukemic HL-60 cells via PPARγ and P38 MAPK signaling pathway].
In: Zhonghua yi xue za zhi, Jg. 90 (2010-08-24), Heft 32, S. 2270-4
Online
academicJournal
Zugriff:
Objective: To investigate the apoptosis-inducing effect of peroxisome proliferator-activated receptor γ (PPARγ) agonist ciglitazone (CGZ) on leukemic HL-60 cells and its mechanisms of action.
Methods: HL-60 cells in vitro culture medium were subject to different concentrations of CGZ (10-50 µmol/L) for 24, 48 and 72 h. MTT assay was used to detect the cell inhibitory rate and agarose gel electrophoresis to observe DNA fragmentation. Flow cytometry (FCM) and Annexin V/PI staining were used to detect CGZ and/or GW9662 (PPARγ antagonist)-induced cell apoptosis. The expression of PPARγ was examined by RT-PCR and Western blotting. The caspase-3 and protein levels in mitogen-activated protein kinase signaling pathways (MAPKs, p-P38, p-ERK and p-JNK) were also detected.
Results: CGZ (over 30 µmol/L) could inhibit the growth of HL-60 cells in both time- and dose-dependent manner. After treatment for 72 h, the cell growth inhibitory rate in 50 µmol/L CGZ (84% ± 11%) treated cells was found more higher than that in both 40 µmol/L and 30 µmol/L CGZ treated cells (72% ± 13%, 59% ± 13%, P < 0.01) and a typical DNA ladder was also observed by agarose gel electrophoresis. The expression of PPARγ was gradually up-regulated by CGZ treatment and could be down-regulated partially by PPARγ antagonist GW9662. The results also revealed that CGZ-induced cell apoptosis (49.7%, 72 h) could not be inhibited thoroughly by GW9662 (36.2%, control:3.2%). It indicated that the CGZ-induced cell apoptosis was partially PPARγ-independent. Western blotting showed a cleavage of caspase-3 zymogen protein and up-regulation of p-P38 protein. Thus it indicated that the activations of caspase-3 and P38 MAPK were involved in CGZ-induced cell apoptosis.
Conclusion: CGZ inhibits cell growth by induction of cell apoptosis in HL-60 cells via PPARγ dependent and independent signaling pathways. The activations of caspase-3 and P38 MAPK may be one of the important mechanisms in CGZ in treated HL-60 cells.
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[Pro-apoptotic effect of ciglitazone in leukemic HL-60 cells via PPARγ and P38 MAPK signaling pathway].
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Autor/in / Beteiligte Person: | Liu, JJ ; Liu, WD ; Liu, XD ; Raj-Shrestha, P ; Liu, PQ ; Huang, HQ ; Wu, CB ; Wang, CZ ; Xu, Y ; Xiao, RZ ; Lin, DJ ; Huang, RW |
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Zeitschrift: | Zhonghua yi xue za zhi, Jg. 90 (2010-08-24), Heft 32, S. 2270-4 |
Veröffentlichung: | Beijing : Zhonghua yi xue hui ; <i>Original Publication</i>: Beijing : Zhonghua yi xue hui., 2010 |
Medientyp: | academicJournal |
ISSN: | 0376-2491 (print) |
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