Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1997;76(3):318–324. doi: 10.1038/bjc.1997.385

Computerized detection of morphological changes to glioma cells during estramustine and ion-channel blocker perifusion.

P Behnam-Motlagh 1, O Jonsson 1, K G Engström 1, R Henriksson 1, K Grankvist 1
PMCID: PMC2224065  PMID: 9252198

Abstract

A perifusion technique for microscopy with computerized detection of early changes in cell morphology during continuous perifusion was used to show that the geometry of cultured glioma cells (MG-251) changes rapidly when they are exposed to estramustine phosphate (EMP). When the cells were exposed to 20 or 40 mg l(-1) EMP, cell volume projected cell area (PCA) rapidly increased. When the Na+,K+-ATPase blocker ouabain (100 micromol l(-1)) was added to the EMP (40 mg l(-1)) perifusion, the acute EMP response was eradicated. When the PCA curve for ouabain alone was subtracted from the curve of combined ouabain and EMP perifusion, the resulting curve showed that ouabain completely blocked the EMP-induced increase in PCA. When the Na+, K+, Cl- co-transport inhibitors bumetanide (10 micromol l(-1)), or furosemide (100 micromol l(-1)), were added to EMP (40 mg l(-1)), the acute increase in PCA seen for EMP alone was also completely blocked. This study shows that inhibitors of ion transmembrane transport can modify EMP-induced cell volume increases. This may be of particular importance since the blockers have been found to interfere also with the cytotoxic function of EMP during cell culture. Thus, it is possible that cell volume changes could serve as a rapid technique for predicting the cytotoxic activity of antineoplastic drugs.

Full text

PDF
318

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bergenheim A. T., Gunnarsson P. O., Edman K., von Schoultz E., Hariz M. I., Henriksson R. Uptake and retention of estramustine and the presence of estramustine binding protein in malignant brain tumours in humans. Br J Cancer. 1993 Feb;67(2):358–361. doi: 10.1038/bjc.1993.65. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bjermer L., von Schoultz E., Norberg B., Henriksson R. Estramustine inhibits monocyte phagocytosis. Prostate. 1988;13(1):49–55. doi: 10.1002/pros.2990130106. [DOI] [PubMed] [Google Scholar]
  3. Engström K. G., Grankvist K., Henriksson R. Early morphological detection of estramustine cytotoxicity measured as alteration in cell size and shape by a new technique of microperifusion. Eur J Cancer. 1991;27(10):1288–1295. doi: 10.1016/0277-5379(91)90099-y. [DOI] [PubMed] [Google Scholar]
  4. Engström K. G., Sävendahl L. Cell volume and shape oscillations in rat type-II somatotrophs at hypotonic conditions. Cytometry. 1995 May 1;20(1):7–13. doi: 10.1002/cyto.990200103. [DOI] [PubMed] [Google Scholar]
  5. Haas M. The Na-K-Cl cotransporters. Am J Physiol. 1994 Oct;267(4 Pt 1):C869–C885. doi: 10.1152/ajpcell.1994.267.4.C869. [DOI] [PubMed] [Google Scholar]
  6. Hartley-Asp B. Estramustine-induced mitotic arrest in two human prostatic carcinoma cell lines DU 145 and PC-3. Prostate. 1984;5(1):93–100. doi: 10.1002/pros.2990050109. [DOI] [PubMed] [Google Scholar]
  7. Henriksson R., Bjermer L., Von Schoultz E., Grankvist K. The effect of estramustine on microtubuli is different from the direct action via oxygen radicals on DNA and cell membrane. Anticancer Res. 1990 Mar-Apr;10(2A):303–309. [PubMed] [Google Scholar]
  8. Hoffmann E. K., Simonsen L. O. Membrane mechanisms in volume and pH regulation in vertebrate cells. Physiol Rev. 1989 Apr;69(2):315–382. doi: 10.1152/physrev.1989.69.2.315. [DOI] [PubMed] [Google Scholar]
  9. Jönsson G., Högberg B., Nilsson T. Treatment of advanced prostatic carcinoma with estramustine phosphate (Estracyt). Scand J Urol Nephrol. 1977;11(3):231–238. doi: 10.3109/00365597709179957. [DOI] [PubMed] [Google Scholar]
  10. Madajewicz S., Catane R., Mittelman A., Wajsman Z., Murphy G. P. Chemotherapy of advanced, hormonally resistant prostatic carcinoma. Oncology. 1980;37(1):53–56. doi: 10.1159/000225402. [DOI] [PubMed] [Google Scholar]
  11. Sandström P. E., Jonsson O., Grankvist K., Henriksson R. Identification of potassium flux pathways and their role in the cytotoxicity of estramustine in human malignant glioma, prostatic carcinoma and pulmonary carcinoma cell lines. Eur J Cancer. 1994;30A(12):1822–1826. doi: 10.1016/0959-8049(94)00236-x. [DOI] [PubMed] [Google Scholar]
  12. Tew K. D., Erickson L. C., White G., Wang A. L., Schein P. S., Hartley-Asp B. Cytotoxicity of estramustine, a steroid-nitrogen mustard derivative, through non-DNA targets. Mol Pharmacol. 1983 Sep;24(2):324–328. [PubMed] [Google Scholar]
  13. Vallbo C., Bergenheim T., Bergh A., Grankvist K., Henriksson R. DNA fragmentation induced by the antimitotic drug estramustine in malignant rat glioma but not in normal brain--suggesting an apoptotic cell death. Br J Cancer. 1995 Apr;71(4):717–720. doi: 10.1038/bjc.1995.140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Wallin M., Deinum J., Fridén B. Interaction of estramustine phosphate with microtubule-associated proteins. FEBS Lett. 1985 Jan 7;179(2):289–293. doi: 10.1016/0014-5793(85)80536-6. [DOI] [PubMed] [Google Scholar]
  15. Yoshida D., Cornell-Bell A., Piepmeier J. M. Selective antimitotic effects of estramustine correlate with its antimicrotubule properties on glioblastoma and astrocytes. Neurosurgery. 1994 May;34(5):863–868. doi: 10.1227/00006123-199405000-00012. [DOI] [PubMed] [Google Scholar]
  16. von Schoultz E., Gunnarsson P. O., Henriksson R. Uptake, metabolism and antiproliferative effect of estramustine phosphate in human glioma cell lines. Anticancer Res. 1989 Nov-Dec;9(6):1713–1716. [PubMed] [Google Scholar]
  17. von Schoultz E., Lundblad D., Bergh J., Grankvist K., Henriksson R. Estramustine binding protein and anti-proliferative effect of estramustine in human glioma cell lines. Br J Cancer. 1988 Sep;58(3):326–329. doi: 10.1038/bjc.1988.212. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES