The 1,4-benzothiazepine derivative JTV-519 is a new type of calcium ion channel 
modulator. We examined the modulatory effect of JTV-519 on the antitumor 
activity of several platinum compounds (cisplatin, carboplatin, and nedaplatin) 
in a human cancer cell line resistant to cisplatin (PC-14 / CDDP) in vitro. 
PC-14 / CDDP cells showed 8-fold resistance to cisplatin compared with the 
parental PC-14 cells as determined by dye formation 
[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT] assay. In 
PC-14 / CDDP, but not PC-14 cells, augmentation of cytotoxicity was observed 
when a nontoxic concentration (10 mM) of JTV-519 was combined with the platinum 
compounds. Increased intracellular cisplatin accumulation was observed in PC-14 
/ CDDP cells in the presence of JTV-519 as measured by atomic absorption assay. 
Therefore, increased cisplatin accumulation was considered to be a possible 
mechanism underlying the reversing effect of JTV-519 on cisplatin resistance. 
These results suggest that JTV-519 is a potent agent reversing cisplatin 
resistance.