The effect of 5'-(N,N-dimethyl)-amiloride on cytotoxic activity of doxorubicin and vincristine in CEM cell lines.
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.
Radváková
I
I
Department of Pharmacology, Faculty of Medicine, Safárik University, Kosice, Slovak Republic.
Mirossay
A
A
Mojzis
J
J
Mirossay
L
L
D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000633:toxicity*; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000633:toxicity*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000633:toxicity*
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D019831:Sodium-Calcium Exchanger; C039465:5-dimethylamiloride; D014750:Vincristine; D000584:Amiloride; D004317:Doxorubicin