Potassium channel blockers quinidine and caesium halt cell proliferation in C6 glioma cells via a polyamine-dependent mechanism.
Potassium channels are ubiquitous in cells and serve essential functions in physiology and pathophysiology. Potassium channel blockers have been shown to block tumour growth by arresting cells at the G(0)/G(1) checkpoint of the cell cycle. We investigated the effect of quinidine and caesium (Cs(+)) on cell proliferation, LDH (lactate dehydrogenase) release, free internal calcium, membrane potential, polyamine concentration, ODC (ornithine decarboxylase) activity and polyamine uptake in C6 glioma cells. The EC(50) for reducing cell proliferation was 112 microM for quinidine, whereas Cs(+) was less effective with an EC(50) of 4.75 mM. KCl or sucrose did not affect proliferation. LDH release was augmented by quinidine. Quinidine caused a transient increase in free internal calcium but decreased calcium after a 48 h incubation period. Further 300 microM quinidine depolarized the cell membrane in a similar range as did 30 mM KCl. Quinidine decreased cellular putrescine beyond detection levels while spermidine and spermine remained unaffected. ODC activity was reduced. Addition of putrescine could not override the antiproliferative effect owing to a reduced activity of the polyamine transporter. Our study indicates that the antiproliferative effect of quinidine is not due to a simple membrane depolarization but is caused by a block of ODC activity.
Weiger
T M
TM
Division of Animal Physiology, Department of Cell Biology, University of Salzburg, Hellbrunnerstrasse 34, A-5020 Salzburg, Austria. thomas.weiger@sbg.ac.at
Colombatto
S
S
Kainz
V
V
Heidegger
W
W
Grillo
M A
MA
Hermann
A
A
D000818:Animals; D001973:Bromodeoxyuridine / Q000493:pharmacokinetics; D002118:Calcium / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D002586:Cesium / Q000494:pharmacology*; D005910:Glioma; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D009955:Ornithine Decarboxylase / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D011802:Quinidine / Q000494:pharmacology*; D051381:Rats
D026902:Potassium Channel Blockers; D002586:Cesium; D007770:L-Lactate Dehydrogenase; D009955:Ornithine Decarboxylase; D001973:Bromodeoxyuridine; D011802:Quinidine; D002118:Calcium