Verapamil potentiates 4'-epidoxorubicin cytotoxicity in a rat hepatoma cell line and in a substrain resistant to 4'-epidoxorubicin.
We have examined the influence of verapamil (VP) on the in vitro effect of 4'-epidoxorubicin (Epi-A) in a rat hepatocarcinoma cell line (MHlCl) and in an Epi-A resistant substrain. A VP concentration of 500 ng/ml (1.1 mumol/l) markedly potentiated the cytotoxic effect of Epi-A in the parent line. The resistant cells grow at an Epi-A concentration of 7500 ng/ml (12.9 mumol/l). This is approximately 15-fold higher than the concentration tolerated by parental cells. In these cells VP reversed the acquired resistance to Epi-A in a concentration dependent manner; thus, a concentration in the range of 500-750 ng/ml (1.1-1.7 mumol/l) of VP restored the sensitivity to Epi-A in the resistant cells. Our results demonstrate that VP increases the sensitivity to Epi-A in hepatocarcinoma cells never exposed to this drug, as well as in hepatocarcinoma cells with acquired Epi-A resistance.
Hall
K S
KS
Department of Clinical Pharmacology, University of Oslo, Rikshospitalet, Norway.
Endresen
L
L
Rugstad
H E
HE
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D004351:Drug Resistance; D004357:Drug Synergism; D015251:Epirubicin / Q000633:toxicity*; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology*
D015251:Epirubicin; D014700:Verapamil