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  • Title: [Mechanisms of arsenic trioxide-induced apoptosis in myeloma cells].
    Author: Zhou Y, Huang X, Cai X.
    Journal: Zhonghua Zhong Liu Za Zhi; 2001 May; 23(3):181-3. PubMed ID: 11783079.
    Abstract:
    OBJECTIVE: To investigate the possible mechanisms of arsenic trioxide (As2O3)-induced apoptosis in multiple myeloma (MM) cell line, and the interactions between As2O3 and all-trans retinoic acid (ATRA) or interferon(IFN)-alpha. METHODS: Multiple myeloma cell lines RPMI 8226 and U266 were treated with As2O3 in combination with dithiothreitol (DTT), buthionine sulfoximine (BSO), ATRA and IFN-alpha. Cell viability was counted by trypan-blue exclusion. Apoptosis was assessed by cell morphology and flow cytometry. Mitochondrial transmembrane potentials (delta psi m) were measured by cellular rhodamine 123 staining intensity on flow cytometry. RESULTS: Glutathione depleting agent BSO at 1.0 mmol/L enhanced, while disulfide bond-reducing agent DTT at 0.2 mmol/L partially antagonized As2O3-induced decline of delta psi m and apoptosis in MM cells. ATRA also induced RPMI 8226 cell apoptosis, but it could not synergize with As2O3. On the other hand, As2O3-induced apoptosis did not occur in U266 cells. In addition, IFN-alpha itself did not inhibit the growth and viability of MM cells, nor did it influence the effects of As2O3 on MM cells. CONCLUSION: As2O3-induced apoptosis of RPMI 8226 multiple myeloma cells involves sulphyhydryl groups. ATRA and IFN-alpha do not synergize with As2O3 in the induction of apoptosis of MM cells.
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