Arsenic trioxide induces multiple myeloma cell apoptosis viadisruption of mitochondrial transmembrane potentials and activation of caspase-3
- Author:
- No author available
- Journal Title:
- CHINESE MEDICAL JOURNAL
- Issue:
- 1
- DOI:
- 10.3760/j.issn:0366-6999.2001.01.004
- Key Word:
- 氧化砷多发性骨髓瘤细胞凋亡线粒体跨膜电位;arsenic trioxide;multiple myeloma;apoptosis;mitochondrial transmembrane potentials
Abstract： Objective To investigate the response of multiple myeloma (MM) cells to arsenic trioxide (As2O3) and their possible mechanisms.Methods Two MM-derived cell lines RPMI8226 and U266 cells were used as in vitro models. Cell apoptosis was assessed by morphology, flow cytometry, and DNA gel electrophoresis. Mitochondrial transmembrane potentials (△Ψm) were evaluated by measuring cellular Rhodamine 123 staining intensity. Protein expression was analyzed using Western blot.Results Zero point one to 0.5?μmol/L As2O3 inhibited cell proliferation and 2.0?μmol/L As2O3 induced cell apoptosis, while 1.0?μmol/L As2O3 inhibited proliferation with a weak degree of apoptosis induction in RPMI8226 and U266 cell lines. As2O3-induced apoptosis was accompanied by mitochondrial transmembrane potentials (△Ψm) collapse and caspase-3 activation in the presence of intact membrane. Glutathione depleter buthionine sulfoximine enhanced, while disulfide bond-reducing agent dithiothreitol partially antagonized As2O3-induced △Ψm collapse and apoptosis in MM cells. All-trans retinoic acid (ATRA) could also induce apoptosis in RPMI8226 cells, but it did not show any cooperative effects with As2O3.Conclusion As2O3 exerts apoptosis-inducing and growth-inhibiting effects on MM cells, and mitochondrium is a pivotal and common target of As2O3 for apoptosis induction.
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