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Apoptotic effect of As2S2 on K562 cells and its mechanism
Jun-E Li1, Wei-Li Wu, Zhen-Yi Wang
1Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China.
Aim:
To investigate the apoptotic effect of As2S2 on K562 cells and its mechanism.
Methods:
The effect of As2S2 on proliferation of K562 cells was determined by counting the number of cells. Apoptosis was assessed by flow cytometry, DNA fragmentation analysis, and morphology observation. Expression of protein was determined by Western blot. RT-PCR was used to evaluate changes in gene expression.
Results:
As2S2 greatly inhibited the proliferation and induced apoptosis of K562 cells in a concentration- and time-dependent manner at the concentration range of 1-5 micromol/L during 24-72 h. Viable cells were decreased to approximately 71 % of control at the concentration of 5 micromol/L after 48-h incubation, 31.4 % after 72-h incubation, and 45.4 % at 3 micromol/L after 72-h incubation. At 3 micromol/L for 72 h, 5 micromol/L for 48 h, and 5 micromol/L for 72 h, the apoptosis rate were 34.4 %, 21.8 %, and 46 % of the treated-cells, respectively. As2S2 decreased the Bcr-Abl fusion protein and protein tyrosine kinase (PTK) activity of c-abl and Bcr-Abl, but it did not change the transcription of bcr-abl assayed. As2S2 also induced apoptosis in fresh mononuclear cells derived from chronic myelogenous leukemia (CML) patients. CML Ph+ leukemia cells were more sensitive to the apoptotic effect of As2S2 than Ph- mononuclear cells (P<0.05).
Conclusion:
As2S2 inhibited the proliferation and induced apoptosis in K562 and fresh CML mononuclear cells. The decline of the Bcr-Abl protein and its PTK activity may play an important role in the apoptotic effect of As2S2. As2S2 may be a useful agent for the treatment of CML.