# Mechanism of action of cisplatin on Na+/K+ ATPase of Caco-2 colon cells in vitro

## TL;DR

This study explores how cisplatin affects the Na+/K+ ATPase in colon cells, revealing a mechanism involving calcium and signaling pathways.

## Contribution

The study identifies a novel indirect mechanism by which cisplatin reduces Na+/K+ ATPase activity in Caco-2 cells.

## Key findings

- Cisplatin reduces Na+/K+ ATPase activity in Caco-2 cells, dependent on the transmembrane chloride gradient.
- Cisplatin increases intracellular calcium, activating p38MAPK and PKA, which inhibit JNK and ATPase activity.
- Fluorescence imaging shows a decrease in membrane ATPase abundance following cisplatin treatment.

## Abstract

Cisplatin is a chemotherapeutic agent that reverts cancerous cells to the apoptotic route. A decrease in the activity of the Na+/K+ ATPase is one of the hallmarks of apoptosis and a major causative factor of the drug-induced nephrotoxicity. Whether cisplatin targets also the colonic ATPase is a question that was addressed in this work using Caco-2 cells as a model. ATPase activity was measured via inorganic phosphate release with and without ouabain, and protein expression was assessed by Western blot. Cisplatin reduced the activity of the Na+/K+ ATPase, an effect that was dependent on the transmembrane chloride gradient but had no effect on the purified enzyme, suggesting an indirect action. Fluorescence imaging showed a decrease in the membrane ATPase abundance. Cisplatin was shown to act by increasing intracellular calcium, triggering a sequential activation of p38MAPK and PKA that results in JNK inhibition and a decrease in the Na+/K+ ATPase activity.