Pharmacological modulation of lung cancer cells for potassium ion depletion.
BACKGROUND
Depletion of intracellular potassium ions (K+) is necessary for cells to shrink, induce DNA fragmentation and activate caspases, events which are features of apoptosis.


METHODS
We used 86Rb+ as a K+ analogue to evaluate the possibility of pharmacologically depleting human pulmonary mesothelioma (P31) and small cell lung cancer (U1690) cells of K+, for future use in studies of apoptosis induction.


RESULTS
The Na+, K+, 2CI(-)-cotransport inhibitor bumetanide transiently inhibited 86Rb+ influx, but when combined with the Na+, K+, ATPase pump inhibitor ouabain there was a marked and lasting (up to 6 h) 86Rb+ influx inhibition. Cellular K+ efflux was augmented by amphotericin B, digitonin and nigericin. Amphotericin B was an effective 86Rb+ efflux stimulator with low cytotoxicity, whereas digitonin caused cell detachment and nigericin increased LDH release in the U1690 cell line, indicating considerable toxicity of the drugs.


CONCLUSIONS
It is possible to efficiently reduce intracellular K+ by persistent K+ influx inhibition and simultaneous K+ efflux stimulation with clinically available drugs.
Andersson
Britta
B
Department of Medical Biosciences, Clinical Chemistry, Umeå University, Umeå, Sweden.
Behnam-Motlagh
Parviz
P
Henriksson
Roger
R
Grankvist
Kjell
K
D000666:Amphotericin B / Q000494:pharmacology; D002034:Bumetanide / Q000494:pharmacology; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D004072:Digitonin / Q000494:pharmacology; D004347:Drug Interactions; D006801:Humans; D007476:Ionophores / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008654:Mesothelioma / Q000188:drug therapy* / Q000378:metabolism; D009550:Nigericin / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000037:antagonists & inhibitors / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism; D012414:Rubidium Radioisotopes / Q000493:pharmacokinetics
D007476:Ionophores; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D012414:Rubidium Radioisotopes; D002034:Bumetanide; D010042:Ouabain; D000666:Amphotericin B; D004072:Digitonin; D009550:Nigericin; D011188:Potassium