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Reversal of Cisplatin Resistance by the 1,4-benzothiazepine Derivative, JTV-519

Reversal of Cisplatin Resistance by the 1,4-benzothiazepine Derivative, JTV-519

T Nakamura, F Koizumi, N Kaneko, T Tamura, F Chiwaki, Y Koh, S Akutagawa, N Saijo, K Nishio

Jpn J Cancer Res. 2001 Jun;92(6):597-602.

PMID: 11429046

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP927871769	2,3,4,5-Tetrahydro-7-methoxy-4-methyl-1,4-benzothiazepine		927871-76-9	Price

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