Ebselen Reduces the Toxicity of Mechlorethamine in A-431 Cells via Inhibition of Apoptosis

Authors


  • Contract Grant Sponsor: Department of Pharmaceutical Sciences (St. John's University).

  • The authors declare that there are no conflicts of interest.

Correspondence to: Blase Billack.

ABSTRACT

A series of test compounds were evaluated for an ability to reduce the toxicity of the nitrogen mustard mechlorethamine (HN2) in vitro. The test compounds included resveratrol, pterostilbene, vitamin C, ebselen, ebselen diselenide, and ebselen-sulfur. Among them, ebselen demonstrated the highest degree of protection against HN2 toxicity. To this end, pretreatment of the cells with ebselen offered protection against the toxicant whereas no protection was observed when cells were first incubated with HN2 and then treated with ebselen. Significant increases in caspase 3 and caspase 9 activities were observed in response to HN2, and ebselen was found to reduce these effects. Taken together, the data presented here indicate that ebselen is an effective countermeasure to nitrogen mustard in vitro, which is worthy of future investigation in vivo. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:313-322, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.21490

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