[Preliminary study on the molecular mechanism of K562 cell apoptosis induced by As2S2].
OBJECTIVE
To investigate the apoptotic inducing effect of As(2)S(2) on K562 cells.


METHODS
The apoptotic inducing effect of As(2)S(2) on K562 cells was determined 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
Apoptosis of K562 cells was induced by 48 - 72 h exposure to 5 micromol/L As(2)S(2). Apoptosis was induced in (34.4 +/- 3.3)% treated cells by 72 h exposure to 3 micro mol/L As(2)S(2), in (21.8 +/- 3.6)% treated cells by 48 h exposure to 5 micromol/L As(2)S(2) and in (46.0 +/- 5.2)% treated cells by 72 h exposure to As(2)S(2) at the same concentration. With 5 micromol/L As(2)S(2), the protein level of Bcr-Abl and JAK2 decreased, while bax expression was upregulated and c-myc was downregulated both in protein and mRNA level. The activity of caspase 3 in K562 cells was increased by As(2)S(2). As(2)S(2) also induced apoptosis of fresh mononuclear cells derived from chronic myelogenous leukemia (CML) patients.


CONCLUSIONS
As(2)S(2) can induce apoptosis of CML cells. The decline of Bcr-Abl may play an important role. The upregulation of bax, increase of the activity of caspase 3, downregulation of c-myc and decrease of JAK2 may also be involved in the mechanism.
Li
Jun-e
JE
Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China.
Sun
Guan-lin
GL
Wu
Ying-li
YL
Wu
Wei-li
WL
D017209:Apoptosis / Q000187:drug effects*; D001152:Arsenicals / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D016044:Fusion Proteins, bcr-abl / Q000032:analysis; D006801:Humans; D053614:Janus Kinase 2 / Q000032:analysis; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000473:pathology; D013440:Sulfides / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000032:analysis
D001152:Arsenicals; C494826:BAX protein, human; D013440:Sulfides; D051028:bcl-2-Associated X Protein; C058317:arsenic disulfide; D016044:Fusion Proteins, bcr-abl; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D053148:Caspase 3