Potentiation of doxorubicin cytotoxicity by the calcium channel blocker verapamil in Ehrlich ascites cells.
The calcium channel blocker verapamil increased the intracellular level of doxorubicin in Ehrlich ascites cells. The high cellular drug level was directly related to the enhancement of the cytotoxicity of the antitumor agent. Tumor-bearing mice pretreated with verapamil showed a 2.3-fold increase in long-term survival effect of doxorubicin together with a pronounced inhibitory effect on tumor DNA, RNA and protein content. This study suggests the possible novel use of verapamil to enhance the antitumor activity of doxorubicin, allowing its dose, and consequently the serious side effects, to be reduced.
al-Gharably
N M
NM
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Osman
A M
AM
al-Shabanah
O A
OA
al-Bekairi
A M
AM
al-Harbi
M M
MM
D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000401:mortality; D004317:Doxorubicin / Q000378:metabolism / Q000627:therapeutic use*; D004357:Drug Synergism; D005260:Female; D051379:Mice; D014700:Verapamil / Q000494:pharmacology*
D004317:Doxorubicin; D014700:Verapamil