Glycolysis in P-glycoprotein-overexpressing human tumor cell lines Effects of resistance-modifying agents

Henricus J. Broxterman, Herbert M. Pinedo, Catharina M. Kuiper, Gerrit J. Schuurhuis, Jan Lankelma

Research output: Contribution to journalArticle

Abstract

We show that drugs, such as verapamil, which reverse multidrug resistance (MDR), in P-glycoprotein-overexpressing tumor cells, increased the rate of lactate production in four human MDR cell lines, but not in the parent, sensitive cell lines. The effect on glycolytic rate was maximal at a medium concentration of 2 μM verapamil. The glycolytic rate in sensitive (A2780) and MDR (2780AD) cells showed the same pH dependence, but the effect of verapamil was seen only in 2780AD cells at all pH values investigated (6.6, 7.4 and 8.2). A series of drugs such as nigericin, oligomycin, amiloride and monensin had similar effects in the two cells. Phorbol myristate acetate increased lactate formation in neither cell line. Verapamil induced an extra amount of ATP consumption in P-glycoprotein-expressing 2780AD cells of approx. 25 pmol/s per 106 cells, which was estimated to be about 10% of cellular energy turnover.

Original languageEnglish (US)
Pages (from-to)405-410
Number of pages6
JournalFEBS Letters
Volume247
Issue number2
DOIs
StatePublished - Apr 24 1989
Externally publishedYes

Keywords

  • Glycolysis
  • Glycoprotein, P-
  • Multidrug resistance
  • Verapamil

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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