Early multidrug resistance, defined by changes in intracellular doxorubicin distribution, independent of P-glycoprotein

G. J. Schuurhuis, H. J. Broxterman, J. H M De Lange, H. M. Pinedo, T. H M Van Heijningen, C. M. Kuiper, G. L. Scheffer, R. J. Scheper, C. K. Van Kalken, J. P A Baak, J. Lankelma

Research output: Contribution to journalArticle

Abstract

Resistance to multiple antitumour drugs, mostly antibiotics or alkaloids, has been associated with a cellular plasma membrane P-glycoprotein (Pgp), causing energy-dependent transport of drugs out of cells. However, in many common chemotherapy resistant human cancers there is no overexpression of Pgp, which could explain drug resistance. In order to characterise early steps in multidrug resistance we have derived a series of P-glycoprotein-positive (Pgp/+) and P-glycoprotein-negative (Pgp/-) multidrug resistant cell lines, from a human non-small cell lung cancer cell line, SW-1573, by stepwise selection with increasing concentrations of doxorubicin. These cells were exposed to doxorubicin and its fluorescence in nucleus (N) and cytoplasm (C) was quantified with laserscan microscopy and image analysis. The fluorescence N/C ratio in parent cells was 3.8 and decreased both in Pgp/+ and Pgp/- cells with increasing selection pressure to 1.2-2.6 for cells with a resistance factor of 7-17. N/C ratios could be restored partly with verapamil only in Pgp/+ cells. N/C ratio measurements may define a general Pgp-independent type of defense of mammalian cells against certain anticancer agents which may precede Pgp expression in early doxorubicin resistance.

Original languageEnglish (US)
Pages (from-to)857-861
Number of pages5
JournalBritish Journal of Cancer
Volume64
Issue number5
StatePublished - 1991
Externally publishedYes

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Multiple Drug Resistance
P-Glycoprotein
Doxorubicin
Antineoplastic Agents
Fluorescence
Cell Line
R Factors
Verapamil
Alkaloids
Drug Resistance
Non-Small Cell Lung Carcinoma
Microscopy
Cytoplasm
Cell Membrane
Anti-Bacterial Agents
Pressure
Drug Therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Schuurhuis, G. J., Broxterman, H. J., De Lange, J. H. M., Pinedo, H. M., Van Heijningen, T. H. M., Kuiper, C. M., ... Lankelma, J. (1991). Early multidrug resistance, defined by changes in intracellular doxorubicin distribution, independent of P-glycoprotein. British Journal of Cancer, 64(5), 857-861.

Early multidrug resistance, defined by changes in intracellular doxorubicin distribution, independent of P-glycoprotein. / Schuurhuis, G. J.; Broxterman, H. J.; De Lange, J. H M; Pinedo, H. M.; Van Heijningen, T. H M; Kuiper, C. M.; Scheffer, G. L.; Scheper, R. J.; Van Kalken, C. K.; Baak, J. P A; Lankelma, J.

In: British Journal of Cancer, Vol. 64, No. 5, 1991, p. 857-861.

Research output: Contribution to journalArticle

Schuurhuis, GJ, Broxterman, HJ, De Lange, JHM, Pinedo, HM, Van Heijningen, THM, Kuiper, CM, Scheffer, GL, Scheper, RJ, Van Kalken, CK, Baak, JPA & Lankelma, J 1991, 'Early multidrug resistance, defined by changes in intracellular doxorubicin distribution, independent of P-glycoprotein', British Journal of Cancer, vol. 64, no. 5, pp. 857-861.
Schuurhuis GJ, Broxterman HJ, De Lange JHM, Pinedo HM, Van Heijningen THM, Kuiper CM et al. Early multidrug resistance, defined by changes in intracellular doxorubicin distribution, independent of P-glycoprotein. British Journal of Cancer. 1991;64(5):857-861.
Schuurhuis, G. J. ; Broxterman, H. J. ; De Lange, J. H M ; Pinedo, H. M. ; Van Heijningen, T. H M ; Kuiper, C. M. ; Scheffer, G. L. ; Scheper, R. J. ; Van Kalken, C. K. ; Baak, J. P A ; Lankelma, J. / Early multidrug resistance, defined by changes in intracellular doxorubicin distribution, independent of P-glycoprotein. In: British Journal of Cancer. 1991 ; Vol. 64, No. 5. pp. 857-861.
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