Killing multiple myeloma cells with the small molecule 3-bromopyruvate: Implications for therapy

Grayna Majkowska-Skrobek, Daria Augustyniak, Paweł Lis, Anna Bartkowiak, Mykhailo Gonchar, Young H. Ko, Peter L. Pedersen, Andre Goffeau, Stanisław Ułaszewski

Research output: Contribution to journalArticle

Abstract

The small molecule 3-bromopyruvate (3-BP), which has emerged recently as the first member of a new class of potent anticancer agents, was tested for its capacity to kill multiple myeloma (MM) cancer cells. Human MM cells (RPMI 8226) begin to lose viability significantly within 8 h of incubation in the presence of 3-BP. The Km (0.3 mmol/l) for intracellular accumulation of 3-BP in MM cells is 24 times lower than that in control cells (7.2 mmol/l). Therefore, the uptake of 3-BP by MM cells is significantly higher than that by peripheral blood mononuclear cells. Further, the IC50 values for human MM cells and control peripheral blood mononuclear cells are 24 and 58 μmol/l, respectively. Therefore, specificity and selectivity of 3-BP toward MM cancer cells are evident on the basis of the above. In MM cells the transcription levels of the gene encoding the monocarboxylate transporter MCT1 is significantly amplified compared with control cells. The level of intracellular ATP in MM cells decreases by over 90% within 1 h after addition of 100 μmol/l 3-BP. The cytotoxicity of 3-BP, exemplified by a marked decrease in viability of MM cells, is potentiated by the inhibitor of glutathione synthesis buthionine sulfoximine. In addition, the lack of mutagenicity and its superior capacity relative to Glivec to kill MM cancer cells are presented in this study.

Original languageEnglish (US)
Pages (from-to)673-682
Number of pages10
JournalAnti-cancer drugs
Volume25
Issue number6
DOIs
StatePublished - Jul 2014

Keywords

  • 3-bromopyruvate
  • A new class of anticancer agents
  • Energy blocker
  • Glivec/Gleevec
  • Multiple myeloma
  • Mutagenicity

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Cancer Research

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  • Cite this

    Majkowska-Skrobek, G., Augustyniak, D., Lis, P., Bartkowiak, A., Gonchar, M., Ko, Y. H., Pedersen, P. L., Goffeau, A., & Ułaszewski, S. (2014). Killing multiple myeloma cells with the small molecule 3-bromopyruvate: Implications for therapy. Anti-cancer drugs, 25(6), 673-682. https://doi.org/10.1097/CAD.0000000000000094