Induction by verapamil of a rapid increase in ATP consumption in multidrug-resistant tumor cells.
A marked increase in cellular ATP consumption was induced by verapamil in the multidrug-resistant (MDR) cell line 2780AD, but not in the drug-sensitive parental cell line A2780. A group of structurally unrelated drugs in concentrations known to reverse MDR, but not the verapamil analog tiapamil, a weak modulator of MDR, had similar effects. This effect was saturated at verapamil concentrations of about 1 microM. These data demonstrate that verapamil concentrations in MDR cells are maintained at a low level at the expense of ATP hydrolysis, and provide a first indication of the amount of metabolic energy used in this process.
Broxterman
H J
HJ
Department of Oncology, Free University Hospital, Amsterdam, The Netherlands.
Pinedo
H M
HM
Kuiper
C M
CM
Kaptein
L C
LC
Schuurhuis
G J
GJ
Lankelma
J
J
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D003630:Daunorubicin / Q000378:metabolism; D004351:Drug Resistance; D005260:Female; D006801:Humans; D006868:Hydrolysis; D009994:Osmolar Concentration; D010051:Ovarian Neoplasms / Q000473:pathology; D010641:Phenotype; D014407:Tumor Cells, Cultured / Q000378:metabolism*; D014700:Verapamil / Q000378:metabolism / Q000494:pharmacology*; D014750:Vincristine / Q000378:metabolism
D014750:Vincristine; D000255:Adenosine Triphosphate; D014700:Verapamil; D003630:Daunorubicin