Tetraarsenic oxide induces apoptosis in U937 leukemic cells through a reactive oxygen species-dependent pathway.
In the present study, we investigated the effect of tetraarsenic oxide (As4O6, 2,4,6,8,9,10-Hexaoxa-1,3,5,7-tetraarsatricyclo[3.3.1.13,7]decane) upon induction of apoptosis in arsenic trioxide (diarsenic oxide, As2O3) resistant U937 leukemic cells. As4O6 induced apoptosis in U937 leukemic cells at much lower concentrations than As2O3 via an early increase of cellular reactive oxygen species (ROS), and a decrease in cellular mitochondrial membrane potential, followed by cytochrome c release and caspase-3 activation. As4O6 generated ROS and induced caspase-3 activation more potently than As2O3 in U937 cells. Incubation of the cells with N-acetyl-L-cysteine and catalase resulted in significant suppression of As4O6-induced apoptotic cell death. These results show that the generation of ROS leads to the consequences associated with apoptosis induced by As4O6. In conclusion, As4O6 might be a new arsenic compound which may induce apoptosis in U937 leukemic cells by activating unique apoptotic signaling mediated by ROS more potently than As2O3, and deserves further evaluation.
Park
In-Chul
IC
Laboratory of Cell Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-240, South Korea.
Park
Myung-Jin
MJ
Woo
Sang-Hyeok
SH
Lee
Hyung-Chahn
HC
An
Sungkwan
S
Gwak
Ho-Shin
HS
Lee
Seung-Hoon
SH
Hong
Seok-Il
SI
Bae
Ill-Ju
IJ
Seo
Kang Moon
KM
Rhee
Chang Hun
CH
D017209:Apoptosis; D001151:Arsenic / Q000494:pharmacology*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000378:metabolism / Q000494:pharmacology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002374:Catalase; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D007938:Leukemia / Q000473:pathology*; D008564:Membrane Potentials; D008928:Mitochondria / Q000473:pathology; D010087:Oxides / Q000378:metabolism / Q000494:pharmacology*; D017382:Reactive Oxygen Species; D013997:Time Factors; D020298:U937 Cells
D001152:Arsenicals; D010087:Oxides; D017382:Reactive Oxygen Species; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D002374:Catalase; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D001151:Arsenic; D000077237:Arsenic Trioxide