This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Szolgay-Daniel, E. Articles by Acker, H. Search for Related Content PubMed PubMed Citation Articles by Szolgay-Daniel, E. Articles by Acker, H.

Effects of Amiloride Treatment on U-118 MG and U-251 MG Human Glioma and HT-29 Human Colon Carcinoma Cells¹

Department of Radiation Sciences, Uppsala University, Box 535, S-751 21 Uppsala, Sweden [E. S-D., J. C.], and Max-Planck Institute for System Physiology, Rheinlanddamm 201, D-4600 Dortmund 1, Federal Republic of Germany [K. Z., G. H., E. D., H. A.]

Human glioma (U-118 MG, U-251 MG) and human colon carcinoma (HT-29) spheroids and monolayers were continuously exposed to amiloride under physiological Na⁺ and HCO₃^- conditions. Amiloride in concentrations of 0.1–0.2 mM inhibited growth, while 0.5 mM or higher induced disintegration of the glioma spheroids within 4–6 days. Growth retardation of the HT-29 spheroids was achieved at concentrations of 0.4–0.5 mM and total growth inhibition and disintegration were achieved at 1.0 mM. Monolayer cultures of glioma cells were also more sensitive to amiloride than those of colon carcinoma cells. The higher amiloride concentrations induced pyknotic nuclei mainly in the central areas of the spheroids where the extracellular pH (pH_e) was low. The amiloride-sensitive glioma spheroids had lower pH_e than the colon carcinoma spheroids. The intracellular pH (pH_i), measured in monolayers, was higher (7.11–7.18) in glioma cells than in colon carcinoma cells (6.94). High concentrations of amiloride, 1.0 mM for 1 h in combination with low Na⁺ concentrations, caused a strong pH_i decrease in glioma cells but only a slight decrease in the colon carcinoma cells. The pH_i measurements in glioma monolayers were carried out after 2–6 days of continuous exposure to 0.1 mM amiloride at physiological levels of Na⁺ and HCO₃^- to simulate the conditions during growth inhibition. After several days this caused, when growth already was inhibited, an acidification of pH_i. Parallel measurements with X-ray microanalysis showed an increase of intracellular sodium and a decrease of intracellular potassium in the gliomas, while no such changes were seen in the colon carcinoma cells under identical conditions. It is concluded that the two glioma cell lines were more sensitive to amiloride, both as monolayers and spheroids, than the corresponding cultures of the colon carcinoma cell line. The inhibition of proliferation by amiloride seemed not to have a clear connection to pH_i regulation.

¹ This work was financially supported by the Swedish National Board of Laboratory Animals 88-22, the Swedish National Board for Technical Development 86-05103P, the Swedish Cancer Society 1079-B90-01XA, Max-Planck-Gesellshaft, Munich, Germany, the Herrmann und Lilly Schilling Stiftung, Essen, Germany, and the BMFT, Bonn, Germany.

² To whom requests for reprints should be addressed.

Received 3/30/90. Accepted 11/12/90.

This article has been cited by other articles:

				M. Hegde, J. Roscoe, P. Cala, and F. Gorin Amiloride Kills Malignant Glioma Cells Independent of Its Inhibition of the Sodium-Hydrogen Exchanger J. Pharmacol. Exp. Ther., July 1, 2004; 310(1): 67 - 74. [Abstract] [Full Text] [PDF]