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Research ArticleExperimental Studies

Pharmacological Modulation of Lung Cancer Cells for Potassium Ion Depletion

BRITTA ANDERSSON, PARVIZ BEHNAM-MOTLAGH, ROGER HENRIKSSON and KJELL GRANKVIST
Anticancer Research July 2005, 25 (4) 2609-2616;
BRITTA ANDERSSON
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PARVIZ BEHNAM-MOTLAGH
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ROGER HENRIKSSON
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KJELL GRANKVIST
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  • For correspondence: kjell.grankvist@medbio.umu.se
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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.

  • 86Rb+
  • potassium ion flux
  • mesothelioma
  • ionophores
  • small cell lung cancer
  • amphotericin B

Footnotes

  • Received March 30, 2005.
  • Accepted May 6, 2005.
  • Copyright© 2005 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
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Anticancer Research: 25 (4)
Anticancer Research
Vol. 25, Issue 4
1 Jul 2005
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Pharmacological Modulation of Lung Cancer Cells for Potassium Ion Depletion
BRITTA ANDERSSON, PARVIZ BEHNAM-MOTLAGH, ROGER HENRIKSSON, KJELL GRANKVIST
Anticancer Research Jul 2005, 25 (4) 2609-2616;

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Pharmacological Modulation of Lung Cancer Cells for Potassium Ion Depletion
BRITTA ANDERSSON, PARVIZ BEHNAM-MOTLAGH, ROGER HENRIKSSON, KJELL GRANKVIST
Anticancer Research Jul 2005, 25 (4) 2609-2616;
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