The development of drug resistance by tumor cells in vitro is accompanied by the development of sensitivity to selenite

Paula B. Caffrey, Gerald Frenkel

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Abstract

The effects of selenite on cell viability and proliferation in a line of drug-sensitive human ovarian tumor (A2780) cells were compared with its effects on a melphalan-resistant derivative of these cells (A2780-ME) which had been developed in vitro (Hamilton et al. (1985) Biochemical Pharmacol., 34, 2583-2586). With the A2780-ME cells there was a 50% decrease in the number of viable cells (i.e. which exclude Trypan Blue dye) after exposure to less than 100 μM selenite for 6 h. In contrast, exposure to more than 300 μM selenite was required to achieve the same effect in the parent line. Similarly, exposure to 10 μM selenite resulted in a 50% decrease in A2780-ME cell proliferation, whereas this treatment had only a small inhibitory effect on proliferation of the parent cells. Thus, the development of melphalan resistance in vitro was accompanied by the development of selenite sensitivity. Pre-exposure of the two cell types to buthionine sulfoximine eliminated the difference in their intracellular glutathione levels, as well as most of their differential sensitivity to selenite. Furthermore, the two cell types did not exhibit a difference in sensitivity to selenodiglutathione, the product of the reaction of selenite with glutathione. Thus, the increase in intracellular glutathione, which has been shown to be responsible for the development of drug resistance in these cells is also responsible for the development of selenite sensitivity.

Original languageEnglish (US)
Pages (from-to)59-65
Number of pages7
JournalCancer Letters
Volume81
Issue number1
DOIs
StatePublished - Jun 15 1994

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All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Molecular Biology
  • Oncology

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