Fiche publication
Date publication
juin 1996
Journal
Anti-cancer drugs
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MERLIN Jean-Louis
Tous les auteurs :
Abderrabi M, Marchal S, Merlin JL
Lien Pubmed
Résumé
The analogs of tiapamil are highly active modifiers of P-glycoprotein-mediated multidrug resistance (MDR) in vitro. The activity of three analogs of tiapamil, Ro 11-2933, Ro 44-5911 and Ro 44-5912, was compared in K562/DXR and MCF-7/DXR cell lines, using flow cytometry for the determination of intracellular daunorubicin accumulation and MTT assays for the cytotoxic evaluation of the modulators combined or not with daunorubicin. Ro 44-5911 and Ro 44-5912 were not intrinsically more toxic than DL-verapamil and exhibited a significantly higher reversing effect. Ro 44-5912 was shown slightly more efficient than Ro 44-5911 for reversing daunorubicin cytotoxicity. Ro 11-2933 was found to be the most potent in modulating MDR but was not significantly more active than Ro 44-5912. These two compounds were able to achieve a near complete reversion (above 80%) at 5 mumol/I. However, the cytotoxicity of Ro 11-2933 was higher with an IC50 near 20 mumol/I in both K562 and MCF7 cell lines. Our results indicate that tiapamil derivatives are promising compounds for MDR modulation. Among them Ro 11-2933 and Ro 44-5912 seem to be particularly interesting for in vivo evaluations.
Mots clés
Adenocarcinoma, drug therapy, Breast Neoplasms, drug therapy, Calcium Channel Blockers, pharmacology, Daunorubicin, pharmacokinetics, Drug Resistance, Multiple, Drug Resistance, Neoplasm, Drug Screening Assays, Antitumor, Flow Cytometry, Humans, Leukemia, Experimental, drug therapy, Propylamines, pharmacology, Tumor Cells, Cultured, Verapamil, analogs & derivatives
Référence
Anticancer Drugs. 1996 Jun;7(4):430-6
