Effects of the 6-alkyl substitution of ellipticine on the uptake by NIH-3T3 cells and on the cytotoxicity.
New ellipticine derivatives of the 2-methyl ellipticinium (NME) series, i.e. 2,6-dimethylellipticinium (6-Me-NME) and 2-methyl-6-n-propylellipticinium (6-Pr-NME), have been studied as cytotoxic compounds. Their uptake by NIH-3T3 cells and efflux have been measured by a sensitive and specific high performance liquid chromatographic assay. These compounds are equitoxic if we compare their cytotoxicity by two methods: growth inhibition and cloning efficiency. However, they accumulate in NIH-3T3 cells at different steady state levels and the efflux rates are not similar. This raises the question of the mode of action of these drugs.
Deprés
J P
JP
Unité de Biochimie et d'Enzymologie: INSERM U140, Institut Gustave-Roussy, Villejuif, France.
Larue
L
L
Paoletti
J
J
Gouyette
A
A
D000470:Alkaloids / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000633:toxicity; D001692:Biological Transport; D001711:Biotransformation; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004611:Ellipticines / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000633:toxicity; D066298:In Vitro Techniques; D007700:Kinetics; D051379:Mice; D012995:Solubility; D013329:Structure-Activity Relationship
D000470:Alkaloids; D000970:Antineoplastic Agents; D004611:Ellipticines; C055499:2-methyl-6-propylellipticine; C034192:ellipticine; C055493:2,6-dimethylellipticine