Poster Presentation 2014 International Biophysics Congress

ABCB1-overexpressing MDCK-II cells are hypersensitive to 3-bromopyruvic acid (#388)

Izabela Sadowska-Bartosz 1 , Jacek Grebowski 2 , Ewa Kepka 3 , Maciej Studzian 2 , Grzegorz Bartosz 2 , Lukasz Pulaski 4
  1. University of Rzeszow, Rzeszów, Poland
  2. Department of Molecular Biophysics, University of Lodz, Lodz, Poland
  3. Department of Molecular Biophysics, University of Lodz, Lodz, Polska
  4. Laboratory of Laboratory of Transcriptional Regulation, Institute of Medical Biology, Polish Academy of Sciences, Lodz, Poland, Institute of Medical Biology PAS, Lodz, Poland

Cancer cells, due to the Warburg effect, are more dependent on glycolysis than normal cells, so glycolytic inhibitor 3-bromopyruvic acid (3-BP) was proposed as a promising candidate for anticancer therapy. Overexpression of multidrug transporters is the main reason of resistance of cancer cells to chemotherapy. As the activity of multidrug transporters imposes an energetic burden on the cells, it can be expected that inhibition of ATP generation may exert a selective cytotoxicity to cells overexpressing multidrug transporters. On these premises, 3-BP can be expected to be efficient also against multidrug-resistant cancer cells.

The aim of this study was to compare the effect of 3-BP on the survival and ATP level in MDCK-II cells and MDCK-II cells overexpressing ABCB1 (PgP) or ABCG2 (BCRP). We found that 3-BP (10-200 μM) induced a decrease of ATP after 1-h incubation in all cell lines studied, the effect being more pronounced in ABCB1-overexpressing cells. After 24 h, ATP level was normalized in all cell lines. Higher concentrations of 3-BP (50 and 200 μM) drastically decreased cell viability, the effect being again more pronounced for ABCB-1 overexpressing cells. The effect of 3-BP on ATP level and survival of MDCK-II and MDCK-II-ABCG2 did not differ significantly. PSC833, inhibitor of ABCB1, ameliorated the toxic effect of 3-BP on MDCK-II-ABCB1 cells and MDCK-II cells while Ko143, inhibitor of ABCG2, was almost ineffective.

These results indicate that 3-BP shows selective toxicity against ABCB1- but not ABCG2-overexpressing cells, apparently due to enhanced ATP depletion.