Thimerosal induces apoptosis and G2/M phase arrest in human leukemia cells.
Thimerosal is an organomercury compound with sulfhydryl-reactive properties. The ability of thimerosal to act as a sulfhydryl group is related to the presence of mercury. Due to its antibacterial effect, thimerosal is widely used as preservatives and has been reported to cause chemically mediated side effects. In the present study, we showed that the molecular mechanism of thimerosal induced apoptosis in U937 cells. Thimerosal was shown to be responsible for the inhibition of U937 cells growth by inducing apoptosis. Treatment with 2.5-5 microM thimerosal but not thiosalicylic acid (structural analog of thimerosal devoid of mercury) for 12 h produced apoptosis, G(2)/M phase arrest, and DNA fragmentation in a dose-dependent manner. Treatment with caspase inhibitor significantly reduced thimerosal-induced caspase 3 activation. In addition, thimerosal-induced apoptosis was attenuated by antioxidant Mn (III) meso-tetrakis (4-benzoic acid) porphyrin (Mn-TBAP). These data indicate that the cytotoxic effect of thimerosal on U937 cells is attributable to the induced apoptosis and that thimerosal-induced apoptosis is mediated by reactive oxygen species generation and caspase-3 activation.
Woo
Kyung Jin
KJ
Department of Immunology, School of Medicine, Keimyung University, Taegu, South Korea.
Lee
Tae-Jin
TJ
Bae
Jae Hoon
JH
Jang
Byeong-Churl
BC
Song
Dae-Kyu
DK
Cho
Jae-We
JW
Suh
Seong-Il
SI
Park
Jong-Wook
JW
Kwon
Taeg Kyu
TK
D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D053938:DNA Fragmentation; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013849:Thimerosal / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D017382:Reactive Oxygen Species; D013849:Thimerosal; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D002118:Calcium