Analysis of the mechanism of proximal tubule S3 region-specific cytotoxicity to cisplatin

Abstract

Cisplatin (CDDP) is an anticancer drug that causes severe kidney damage, especially in the S3 region of the proximal tubule. We showed that cytotoxicity to CDDP, carboplatin (CAR), and oxaliplatin (OXA) is the highest in the S3-derived cells. The S3-specific toxicity could not be explained by accumulation of Pt. Since the highest amount of Pt uptake was found 15 minutes after the exposure, the cytotoxicity by 15 min-exposure to CDDP, CAR, and OXA was examined. As a result, even the 15-min exposure to these drugs caused the highest cytotoxicity in S3 cells, suggesting the importance of shout-term cellular responses.