title: Thimerosal induces apoptosis and G2/M phase arrest in human leukemia cells.
abstract: 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.
authors.affiliation: Department of Immunology, School of Medicine, Keimyung University, Taegu, South Korea.
authors.forename: Kyung Jin
authors.initials: KJ
authors.lastname: Woo
authors.forename: Tae-Jin
authors.initials: TJ
authors.lastname: Lee
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Bae
authors.forename: Byeong-Churl
authors.initials: BC
authors.lastname: Jang
authors.forename: Dae-Kyu
authors.initials: DK
authors.lastname: Song
authors.forename: Jae-We
authors.initials: JW
authors.lastname: Cho
authors.forename: Seong-Il
authors.initials: SI
authors.lastname: Suh
authors.forename: Jong-Wook
authors.initials: JW
authors.lastname: Park
authors.forename: Taeg Kyu
authors.initials: TK
authors.lastname: Kwon
mesh_terms: 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
chemical_list: D017382:Reactive Oxygen Species; D013849:Thimerosal; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D002118:Calcium