Cisplatin, a platinum-based drug widely used in cancer therapy, is thought to kill cancer cells by causing the induction of apoptosis. We have found that in the KB-3-1 human epidermoid cancer cell line, cisplatin treatment causes a potentiation of activity of the volume-sensitive, outwardly rectifying (VSOR) Cl− channel, which has previously been shown to play an important role in apoptosis. Caspase-3 activation and cell death induced by cisplatin treatment were reduced by inhibition of the VSOR Cl− channel with the blocker DIDS, suggesting that activity of the channel contributes to cisplatin sensitivity. Furthermore, we have found that in the KCP-4 cell line, a cisplatin-resistant derivative of the KB-3-1 cell line, VSOR Cl− channel activity is virtually absent. We hypothesized that the lack of the channel activity contributes to the cisplatin resistance of these cells, and to test this, we attempted to restore the channel activity. Treatment with trichostatin A (TSA) or apicidin, a histone deacetylase inhibitor, caused VSOR Cl− channel function to be partially restored. The TSA-induced restoration reduced the cisplatin resistance of KCP-4 cells, as measured by caspase-3 activity and cell viability assays. DIDS inhibited the reduction in cisplatin resistance. We conclude that activity of the VSOR Cl− channel is involved in the response of KB-3-1 and KCP-4 cells to cisplatin treatment. [J Physiol Sci. 2007;57 Suppl:S20]
