Thimerosal induces apoptosis and G2/M phase arrest in human leukemia cells

Molecular Carcinogenesis
Kyung Jin WooTaeg Kyu Kwon

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.

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Citations

Dec 17, 2011·Cancer Prevention Research·Jyotsana SinghalSharad S Singhal
Feb 20, 2014·Metallomics : Integrated Biometal Science·Imke PieperTanja Schwerdtle
Dec 31, 2008·Mutation Research·Rodrigo FrancoMihalis I Panayiotidis
Dec 14, 2007·Toxicology·GianPaolo Guzzi, Caterina A M La Porta
Aug 8, 2009·Human & Experimental Toxicology·L N KuoC R Jan
Aug 19, 2007·Toxicological Sciences : an Official Journal of the Society of Toxicology·Shiuh-Inn LiuChung-Ren Jan

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