Pharmacological Modulation of Lung Cancer Cells for Potassium Ion Depletion

Abstract

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. Materials and 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⁺, 2Cl^--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. Conclusion: It is possible to efficiently reduce intracellular K⁺ by persistent K⁺ influx inhibition and simultaneous K⁺ efflux stimulation with clinically available drugs.