title: Digital cell image analysis of verapamil-induced effects in chemosensitive and chemoresistant neoplastic cell lines.
abstract: We used chemosensitive and chemoresistant variants of the neoplastic mouse MXT mammary and human J82 and T24 bladder cell lines to characterize verapamil-induced cell proliferation and morphonuclear modifications in drug-treated and untreated cells. Chemoresistance to vinorelbine (Navelbine, a Vinca alkaloid derivative), to DIAM3 (an investigational alkylating compound) and to Adriamycin (an intercalating agent) in the presence or absence of verapamil was monitored by means of the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The results showed that verapamil restored a significant level of chemosensitivity in doses such as 1 microM or 10 microM in the three chemoresistant variants. The digital cell image analysis of Feulgen-stained T24-resistant cell nuclei revealed that verapamil restored the drug-treated cell kinetics and morphonuclear features observed in the sensitive counterpart especially with respect to the effects of Adriamycin. Interestingly, verapamil induced a highly significant chromatin decondensation in resistant but not in sensitive variants. Such verapamil-induced decondensation may favour the accessibility of drugs to their DNA targets. Therefore, in addition to the well-known action of the drug on the influx of a cytotoxic compound from the cellular to the intracellular compartment, verapamil might also favour the accessibility of the nucleus, to the drug.
authors.affiliation: Division de Cancérologie Expérimentale I, Centre de Recherche Pierre Fabre, Castres, France.
authors.forename: C
authors.initials: C
authors.lastname: Etiévant
authors.forename: O
authors.initials: O
authors.lastname: Pauwels
authors.forename: R
authors.initials: R
authors.lastname: Kiss
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001388:Aziridines / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D003959:Diamines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D004347:Drug Interactions; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D009943:Organophosphorus Compounds / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014700:Verapamil / Q000494:pharmacology*; D014747:Vinblastine / Q000031:analogs & derivatives / Q000494:pharmacology; D000077235:Vinorelbine
chemical_list: D000970:Antineoplastic Agents; D001388:Aziridines; D003959:Diamines; D009943:Organophosphorus Compounds; D014747:Vinblastine; D004317:Doxorubicin; C064571:DIAM 3; D014700:Verapamil; D000077235:Vinorelbine