Effects of arsenic trioxide on cell death, reactive oxygen species and glutathione levels in different cell types.
Arsenic trioxide (ATO) can regulate many biological functions such as apoptosis and differentiation. We evaluated the effects of ATO on various cell types such as cervical cancer HeLa cells, pulmonary adenocarcinoma Calu-6 and A549 cells, calf pulmonary artery endothelial cells (CPAEC), human umbilical vein endothelial cells (HUVEC) and human pulmonary fibroblast (HPF) cells in relation to cell growth, cell death and reactive oxygen species (ROS) and glutathione (GSH) levels. The growth of HeLa and Calu-6 cells was inhibited by ATO with an IC50 of approximately 15 microM at 24 h. A549 cell growth was not inhibited by 15 microM ATO. The susceptibility to ATO in CPAEC and HUVEC was similar to that in HeLa cells. The IC50 of ATO in HPF cells was approximately 40 microM. ATO induced apoptosis in HeLa, CPAEC and HUVEC, which was accompanied by the loss of mitochondrial membrane potential (DeltaPsim). However, ATO did not strongly trigger apoptosis in Calu-6, A549 and HPF cells. ATO increased or decreased the ROS level including O2.- and GSH levels depending on the incubation dose and cell type. In conclusion, ATO differentially affected cell growth inhibition and death depending on the incubation dose and cell type. The changes in ROS and GSH levels by ATO were not tightly correlated with the level of cell death. Our present data provide useful information for the action of ATO in various cell types in relation to cell growth, cell death, ROS and GSH levels.
Han
Yong Hwan
YH
Department of Physiology, Medical School, Centers for Healthcare Technology Development Institute for Medical Sciences, Chonbuk National University, JeonJu 561-180, Republic of Korea.
Moon
Hwa Jin
HJ
You
Bo Ra
BR
Kim
Sung Zoo
SZ
Kim
Suhn Hee
SH
Park
Woo Hyun
WH
D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002417:Cattle; D016923:Cell Death / Q000187:drug effects*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D010087:Oxides / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D001152:Arsenicals; D006131:Growth Inhibitors; D010087:Oxides; D017382:Reactive Oxygen Species; D005978:Glutathione; D000077237:Arsenic Trioxide