[Mechanisms of arsenic trioxide-induced apoptosis in myeloma cells].
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.


CONCLUSIONS
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.
Zhou
Y
Y
Zhongshan Hospital, Shanghai Medical University, Shanghai 200032, China.
Huang
X
X
Cai
X
X
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D004229:Dithiothreitol / Q000494:pharmacology; D004347:Drug Interactions; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D009101:Multiple Myeloma / Q000473:pathology; D010087:Oxides / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001152:Arsenicals; D016898:Interferon-alpha; D010087:Oxides; D019328:Buthionine Sulfoximine; D014212:Tretinoin; D000077237:Arsenic Trioxide; D004229:Dithiothreitol