Arsenic induces apoptosis in B-cell leukaemic cell lines in vitro: activation of caspases and down-regulation of Bcl-2 protein.
We showed that arsenic inhibited the cell growth of four B-cell leukaemia cell lines of 11 various cell lines in vitro. In two of these four lines, KOCL44 and LyH7, apoptosis was identified by morphological and nucleosomal DNA fragmentation studies. Three of the four B-cell lines that were growth inhibited were acute infantile leukaemia with t(11;19)(q23;p13) translocations involving the MLL gene that encodes the transcriptional factor Drosophila trithorax. The arsenic-induced apoptosis in KOCL44 and LyH7 cells was found to be linked to caspases by Western blot and enzymological analyses. The amount of Bcl-2 was reduced during apoptosis in LyH7 as judged by Western blot analysis. We concluded that combined activation of the caspases and down-regulation of Bcl-2 could determine the fate of B-cell leukaemic cells in response to arsenic.
Akao
Y
Y
Gifu International Institute of Biotechnology, Yagi Memorial Park, Mitake, Japan.
Mizoguchi
H
H
Kojima
S
S
Naoe
T
T
Ohishi
N
N
Yagi
K
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D015153:Blotting, Western; D053938:DNA Fragmentation; D015536:Down-Regulation; D004587:Electrophoresis, Agar Gel; D006801:Humans; D015448:Leukemia, B-Cell / Q000378:metabolism / Q000473:pathology*; D009363:Neoplasm Proteins / Q000378:metabolism; D010087:Oxides / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D001152:Arsenicals; D009363:Neoplasm Proteins; D010087:Oxides; D019253:Proto-Oncogene Proteins c-bcl-2; D000077237:Arsenic Trioxide