Chlorpromazine enhancement of epirubicin cytotoxicity in vitro: effects on plasma membrane and DNA damage.
The frequently used antiemetic drug chlorpromazine has previously been shown to augment anthracycline-induced toxicity to cultured Chinese hamster fibroblasts measured by cloning /1/. We therefore tested the ability of chlorpromazine to affect the induction of plasma membrane and DNA damage by the anthracycline epirubicin. Plasma membrane damage was determined by the cells' ability to accumulate 86Rb after incubation with 10 mg/l epirubicin, and DNA damage was determined by measuring the amount of DNA precipitation after incubation with 25 mg/l epirubicin. The epirubicin-induced inhibition of 86Rb-accumulation as well as the enhancement of epirubicin-induced DNA damage were markedly enhanced in the presence of chlorpromazine. Chlorpromazine augmentation of epirubicin cytotoxicity, including plasma membrane and DNA damage, may be due to its calmodulin antagonistic action and related to the maintenance integrity. Further studies are justified to evaluate the effects of chlorpromazine influence on antineoplastic drug action in vitro and in vivo.
Mothlagh
P B
PB
Department of Clinical Chemistry, University Hospital, Umeå, Sweden.
Henriksson
R
R
Grankvist
K
K
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D002746:Chlorpromazine / Q000494:pharmacology*; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D015251:Epirubicin / Q000633:toxicity*; D005347:Fibroblasts / Q000187:drug effects; D012413:Rubidium / Q000378:metabolism; D012414:Rubidium Radioisotopes
D012414:Rubidium Radioisotopes; D015251:Epirubicin; D012413:Rubidium; D002746:Chlorpromazine