[Mechanism of arsenic trioxide-induced cytotoxicity on multiple myeloma cells].
OBJECTIVE
Multiple myeloma (MM), a plasma cell tumor, is difficult to cure by now. Previous study showed that As2O3 could inhibit the proliferation and induce the apoptosis of myeloma cell in vitro. The aim of this study was to explore the possible mechanism of arsenic trioxide (As2O3) on multiple myeloma cells.


METHODS
The cytotoxic effects of As2O3 on five myeloma cell lines U266, SKO-007, LP-1, HS-Sultan, and KM3 were examined using MTT bioassay, and the concentration of 50% growth inhibition (IC(50)) was calculated. The synergistic or antagonistic effects of menadione (VK(3)), N-acetyl-cysteine (NAC), and reduced glutathione (GSH) combined with As2O3 were also examined. The cellular GSH levels in five MM cell lines and its changes in U266 cells after treated with As2O3, VK(3), NAC, and exogenous GSH were determined by colorimetric assay, and the relationship between IC(50) and cellular GSH levels was analyzed.


RESULTS
As2O3 inhibited the proliferation of all five myeloma cells, but with different sensitivity. GSH contents in five MM cells were correlated with its IC(50) significantly (r=0.87,P< 0.05). Oxidant VK(3) had significant synergistic effect with As2O3, and antioxidants NAC and GSH partly blocked the growth inhibition of As2O3. Both As2O3 and VK(3) decreased the GSH contents, NAC and GSH increased them contrarily.


CONCLUSIONS
One of the mechanisms of effect of As2O3 on myeloma cells may be through decreasing the cellular GSH levels and inducing myeloma cell apoptosis.
Chen
Yu-Bao
YB
Department of Hematology, Changzheng Hospital, The Second Military Medical University, Shanghai, PR China. cybllx@sh163.net
Hou
Jian
J
Fu
Wei-Jun
WJ
Ding
Si-Qi
SQ
Wang
Dong-Xing
DX
Yuan
Zhen-Gang
ZG
Kong
Xian-Tao
XT
D000111:Acetylcysteine / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004347:Drug Interactions; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D009101:Multiple Myeloma / Q000473:pathology*; D010087:Oxides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D024483:Vitamin K 3 / Q000494:pharmacology
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D024483:Vitamin K 3; D005978:Glutathione; D000077237:Arsenic Trioxide; D000111:Acetylcysteine