title: Nimodipine as a modulator of resistance to doxorubicin in human colon-adenocarcinoma cells.
abstract: The potential of the dihydropyridine nimodipine (NIMO), a drug currently used for cerebrovascular disorders, in modulating the cytotoxicity of doxorubicin (DX) was investigated, in comparison to verapamil (VER), in human colon adenocarcinoma cell lines sensitive (LoVo) or resistant (LoVo/DX) to anthracycline. NIMO selectively enhanced DX activity in the resistant cell line. In particular, the DX concentration able to inhibit cell growth by 50% was reduced by 2.6 to 5.7-fold as a function of the time of exposure to the modulator. The increase in DX accumulation in LoVo/DX nuclei after exposure to NIMO was about 4-fold that observed in the nuclei of resistant cells exposed to DX alone. Similar results were obtained in LoVo/DX cells following treatment with equimolar concentrations of VER. Again, both NIMO and VER failed to interfere with the immunoreactivity of LoVo/DX cells to the MRK16 monoclonal antibody. NIMO did not inhibit H-3-azidopine binding to LoVo/DX cells, but, unlike VER, it caused a selective hyperpolarization of the cell membrane in resistant cells.
authors.affiliation: IST NAZL STUDIO & CURA TUMORI,DIV ONCOL SPERIMENTALE C,I-20133 MILAN,ITALY. OSPED MAGGIORE,IST CLIN MED GEN,MILAN,ITALY. IST CODIVILLA PUTTI,CNR,IST CITOMORFOL NORMALE & PATOL,BOLOGNA,ITALY.
authors.forename: A
authors.initials: A
authors.lastname: Bearzatto
authors.forename: A
authors.initials: A
authors.lastname: Saino
authors.forename: N
authors.initials: N
authors.lastname: Zaffaroni
authors.forename: A
authors.initials: A
authors.lastname: Costa
authors.forename: S
authors.initials: S
authors.lastname: Santi