The Inhibition by Oxaliplatin, a Platinum-Based Anti-Neoplastic Agent, of the Activity of Intermediate-Conductance Ca²⁺-Activated K⁺ Channels in Human Glioma Cells.
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 Ca(2+)-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 Ca(2+)-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.
Mei-Han
MH
Huang
Yan-Ming
YM
Huang
Sheng-Nan
SN
Wu
D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003022:Clotrimazole / Q000494:pharmacology; D005910:Glioma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects*; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000494:pharmacology*; D000077150:Oxaliplatin; D018408:Patch-Clamp Techniques; D010984:Platinum / Q000737:chemistry; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism
D000970:Antineoplastic Agents; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D009944:Organoplatinum Compounds; D011720:Pyrazoles; D012333:RNA, Messenger; C411671:TRAM 34; D000077150:Oxaliplatin; D010984:Platinum; D003022:Clotrimazole