Potentiation of 4'-(9-acridinylamino)methanesulphon-m-anisidine) action by verapamil.
Verapamil was shown to increase growth inhibition and decrease viability of PY815 mastocytoma cells treated with the anti-cancer drug mAMSA 4'-(9-acridinylamino)methanesulphon-m-anisidide (mAMSA) or its normally inactive congener, 4'-(9-acridinylamino)methanesulphon-o-anisidide (oAMSA). Verapamil also potentiated the effect of sub-optimal concentrations of mAMSA or oAMSA on DNA scission in intact cells. Uptake of [14C]mAMSA by PY815 cells was considerably enhanced, while efflux of [14C]mAMSA from precharged cells was inhibited by verapamil. It is concluded that verapamil potentiates the action of mAMSA on PY815 cells in culture by reducing efflux of drug from the cells. The possibility that verapamil may affect systems that sequester or metabolize AMSA drugs is suggested.
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D000609:Aminoacridines / Q000378:metabolism / Q000494:pharmacology*; D000677:Amsacrine / Q000031:analogs & derivatives; D000818:Animals; D002460:Cell Line; D004273:DNA, Neoplasm / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D012515:Mast-Cell Sarcoma / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D013329:Structure-Activity Relationship; D014700:Verapamil / Q000494:pharmacology*
D000609:Aminoacridines; D004273:DNA, Neoplasm; D000677:Amsacrine; C033073:4'-(9-acridinylamino)methanesulfon-o-anisidide; D014700:Verapamil