TY - JOUR T1 - Pharmacological Modulation of Lung Cancer Cells for Potassium Ion Depletion JF - Anticancer Research JO - Anticancer Res SP - 2609 LP - 2616 VL - 25 IS - 4 AU - BRITTA ANDERSSON AU - PARVIZ BEHNAM-MOTLAGH AU - ROGER HENRIKSSON AU - KJELL GRANKVIST Y1 - 2005/07/01 UR - http://ar.iiarjournals.org/content/25/4/2609.abstract N2 - 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. Copyright© 2005 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved ER -