Apoptosis mechanism induced by BH3 mimetic S1 in human leukemia cell line K562
10.3760/cma.j.issn.1009-9921.2012.12.007
- VernacularTitle:BH3模拟物S1诱导人类白血病细胞株K562凋亡的作用机制
- Author:
Jingyu LI
;
Yubo LIU
;
Ting SONG
;
Xiaoyun SHEN
;
Zhichao ZHANG
- Publication Type:Journal Article
- Keywords:
K562 cells;
S1;
Apoptosis;
bcl-2
- From:
Journal of Leukemia & Lymphoma
2012;21(12):723-726
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the apoptosis mechanism induced by BH3 mimetic S1 in human leukemia cell line K562.Methods Cell viability was detected by XTT to S1 in leukemia cell line K562.K562 cells was incubated with S1 for different time,the apoptosis rate of K562 cells was determined by flow cytometry analysis.Caspase-3,-8,and-9 activities were measured by absorption spectra.Co-immunoprecipitation was used to analyze the releasing of bax,bak from bcl-2 and mcl-1.Results Compared with control group,a dose-dependent increase in apoptosis coincided with a dose-dependent decrease in cell viability following S1 treatment suggested that S1 inhibits cell proliferation through the induction of apoptosis.The IC50 value at 24 h for S1 was 13.5 μ mol/L.Exposure of K562 cells to S1 for 12 h resulted in a time-dependent increase in FITC-Annexin-positive/PI-negative early apoptotic cells.The strong increase of FITC Annexin/PI doublepositive cells after a 24 h treatment indicated a shift to late apoptosis.S1 activated Caspase-3 and-9,but not Caspase-8 indicated that S1 induced K562 cells apoptosis via the intrinsic pathway.K562 cells treated with 5 μmol/L of S1 showed a disruption in bcl-2/bax,mcl-1/bak complexes after 8 h S1 treatment.Conclusion The main mechanism that S1 induces K562 cells apoptosis might be through the inhibition of bcl-2/bax,mcl-1/bak complexes dissociation.
