The Effect of
5´-(N,N-Dimethyl)-amiloride on Cytotoxic
Activity of Doxorubicin and Vincristine in CEM
Cell Lines
I. RADVÁKOVÁ, A.
MIROŠŠAY, J. MOJŽIŠ, L. MIROSSAY
Department
of Pharmacology, Faculty of Medicine, Šafárik
University, Košice, Slovak Republic
Received
March 3, 2000
Accepted October 20, 2000
Summary
Intracellular
pH (pHi) plays an important role in anticancer
drug accumulation in cancer cells. Resistant
cells often express membrane P-glycoprotein
responsible for active drug extrusion and
participating in increased pHi. In the present
paper, we report on the influence of
Na+/H+-exchanger inhibitor,
5´-(N,N-dimethyl)-amiloride (AMI), on the
cytotoxic effects of doxorubicin (DOXO) and
vincristine (VCR) in the parental CEM, and
resistant CEM/DNR and CEM/VCR cell lines. The
obtained results revealed a potentiating effect
of AMI to both anticancer drugs in parental CEM
line. However, AMI did not significantly
potentiate the effect of DOXO or VCR in resistant
CEM cell lines. We conclude, that inhibition of
Na+/H+-exchanger by AMI is not sufficient for
reversal of drug resistance in the tested CEM/DNR
and CEM/VCR cell lines and the possible change in
pHi does not affect the mechanisms of cell
resistance.
Key
words
Amiloride
· CEM cell lines · Anticancer drugs ·
Resistance · Intracellular pH
Reprint
requests
Assoc. Prof. L. Mirossay, M.D. Ph.D., Department
of Pharmacology, Faculty of Medicine, University
of P. J. Šafárik,
Tr. SNP 1, 040 66 Košice, Slovak Republic, fax:
+421 95 6 428 524, e-mail: mirossay@central.medic.upjs.sk
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