[Mechanisms underlying the effect of arsenic trioxide on proliferation inhibition and apoptosis induction in myeloma cell line u266].
The aim of this study was to explore the mechanisms underlying effect of arsenic trioxide (As2O3) on myeloma cell line U266 in vitro. The viability and apoptosis of U266 cells were observed by MTT assay, flow cytometry and DNA agarose gel electrophoresis. The expression of hTERT mRNA was assessed by RT-PCR analysis. The variation of procaspase-3, bcl-2 and hTERT protein expression were detected by Western blot. The results indicated that the As2O3 could inhibit the growth of U266 cells significantly and the concentration of 50% growth inhibition (IC50) was 2 micromol/L. After treatment with 2.5 micromol/L As2O3 at 24, 48 and 72 hours, a dose- and time-dependent apoptosis of U266 cells could be observed. After treating U266 cells with 2 micromol/L As2O3 at different time points, a time-dependent reduction of procaspase-3, hTERT mRNA and protein was found without any change of bcl-2 expression. It is concluded that the As2O3 can change the mitochondrial transmembrane potential, initiating the mitochondial apoptosis pathway, leading in turn to caspase-3 activation, and inducing the apoptosis of U266 cells. These findings suggest that the reduction of hTERT plays a critical role in the apoptosis of U266 cells induced by As2O3.
Yu
Qing-Hong
QH
Department of Hematology, Union Hospital Affiliated to Fujian Medical University, Fuzhou 350001, China.
Zhan
Rong
R
Huang
Hao-Bo
HB
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D009101:Multiple Myeloma / Q000473:pathology*; D010087:Oxides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D019098:Telomerase / Q000378:metabolism
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D012333:RNA, Messenger; C509186:TERT protein, human; D019098:Telomerase; D053148:Caspase 3; D000077237:Arsenic Trioxide