Selectivity of N-[2-(dimethylamino)ethyl]acridine-4-carboxamide towards Lewis lung carcinoma and human tumour cell lines in vitro.
N-[2-(Dimethylamino)ethyl]acridine-4-carboxamide (AC; NSC 601316) is a chemically novel antitumour agent which is thought to interact with DNA topoisomerase II and which has DNA binding properties which are distinct from other acridine derivatives such as amsacrine and its disubstituted analogue CI-921. AC is one of the most active agents, experimental or clinical, against the Lewis lung carcinoma in mice. AC is the first acridine derivative in our hands to show higher activity against cultured Lewis lung cells than against leukaemia lines. AC is more active against two human leukaemia cell lines (U-937 and Jurkat) than against a melanoma line (MM-96) and is inactive against the HT-29 human colon line. With all cell lines tested, cytotoxicity was higher at AC concentrations of 3-6 microM than at 15-20 microM. AC at a concentration of 20 microM inhibited the cytotoxicity of amsacrine and CI-921, but not that of another topoisomerase-directed drug doxorubicin. A Lewis lung line which had been cultured for a long period was less sensitive than a line freshly isolated from mice, but sensitivity of the cultured line recovered after it was multiply passaged in vivo. Long-term cultures may therefore be less appropriate than short-term cultures for predicting effectiveness of AC in vivo.
Finlay
G J
GJ
Cancer Research Laboratory, University of Auckland School of Medicine, New Zealand.
Baguley
B C
BC
D000166:Acridines; D000609:Aminoacridines / Q000627:therapeutic use*; D000677:Amsacrine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000037:antagonists & inhibitors; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D051379:Mice; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014410:Tumor Stem Cell Assay
D000166:Acridines; D000609:Aminoacridines; D000970:Antineoplastic Agents; D000677:Amsacrine; D004317:Doxorubicin; C058332:N-(2'-(dimethylamino)ethyl)acridine-4-carboxamide; C042315:asulacrine