The Inhibition by Oxaliplatin, a Platinum-Based Anti-Neoplastic Agent, of the Activity of Intermediate-Conductance Ca2+-Activated K+ Channels in Human Glioma Cells

Abstract

Oxaliplatin (OXAL) is a third-generation organoplatinum which is effective against advanced cancer cells including glioma cells. How this agent and other related compounds interacts with ion channels in glioma cells is poorly understood. OXAL (100 µM) suppressed the amplitude of whole-cell K⁺ currents (I_K); and, either DCEBIO or ionomycin significantly reversed OXAL-mediated inhibition of I_K in human 13-06-MG glioma cells. In OXAL-treated cells, TRAM-34 did not suppress I_K amplitude in these cells. The intermediate-conductance Ca²⁺-activated K⁺ (IK_Ca) channels subject to activation by DCEBIO and to inhibition by TRAM-34 or clotrimazole were functionally expressed in these cells. Unlike cisplatin, OXAL decreased the probability of IK_Ca-channel openings in a concentration-dependent manner with an IC₅₀ value of 67 µM. No significant change in single-channel conductance of IK_Ca channels in the presence of OXAL was demonstrated. Neither large-conductance Ca²⁺-activated K⁺ channels nor inwardly rectifying K⁺ currents in these cells were affected in the presence of OXAL. OXAL also suppressed the proliferation and migration of 13-06-MG cells in a concentration- and time-dependent manner. OXAL reduced IK_Ca-channel activity in LoVo colorectal cancer cells. Taken together, the inhibition by OXAL of IK_Ca channels would conceivably be an important mechanism through which it acts on the functional activities of glioma cells occurring in vivo.