Mechanism of cross-resistance to cisplatin in a mitomycin C-resistant human bladder cancer cell line

✍ Scribed by Shivendra V. Singh; Bing H. Xu; Jitesh P. Jani; Erling O. Emerson; Mary G. Backes; Christopher Rihn; Domenic Scalamogna; Nancy Stemmler; Susan Specht; Kurt Blanock; Arthur Katoh; Vicram Gupta

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: French
• Weight: 730 KB
• Volume: 61
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910610326

✦ Synopsis

This study was undertaken to elucidate the mechanism@) of cross-resistance to cisplatin (CDDP) in a mitomycin C (MMC)resistant human bladder cancer cell line, J82/MMC. The J82/ MMC cell line displayed 2-to 3-fold cross-resistance to CDDP and carboplatin when compared to the parental )82/WT cells. Drug uptake studies revealed that cross-resistance to CDDP in the J82/MMC cell line was independent of reduced platinum accumulation. The )82/MMC cell line exhibited approximately a I .S-fold resistance to cadmium chloride, an indicator for increased metallothionein (MT) content, when compared to the J82/WT cells. Northern blot analysis showed a 2.7-fold higher level of MT-II, mRNA in the J82/MMC cell line compared with J82/WT. We have reported previously that, whereas glutathione (GSH) level is comparable in these cells, GSH transferase (GST) activity is significantly higher in the )82/MMC cell line compared with J82/WT. Results of the present study showed that the elevated GST activity in the J82/MMC cell line was due to an over-expression of n-type GST protein. Although buthionine-S,R-sulfoximine (BS0)-induced GSH depletion significantly enhanced CDDP cytotoxicity in both cell lines, the magnitude of potentiation was markedly higher in )82/MMC cells (about 2. I -fold) relative to )82/WT (about I .6-fold). Our results suggest that cross-resistance to CDDP in the J82/MMC cell line may be due to alterations in cellular thiols.