Genistein modulates the decreased drug accumulation in non-P-glycoprotein mediated multidrug resistant tumour cells.

In tumour cells the pharmacological basis for multidrug resistance (MDR) often appears to be a reduced cellular cytostatic drug accumulation caused by the drug efflux protein, P-glycoprotein (Pgp MDR), or by other drug transporters (non-Pgp MDR). Here we report the reversal of the decreased daunorub...

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Autores principales: Versantvoort, C. H., Schuurhuis, G. J., Pinedo, H. M., Eekman, C. A., Kuiper, C. M., Lankelma, J., Broxterman, H. J.
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 1993
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1968712/
https://www.ncbi.nlm.nih.gov/pubmed/8105867
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author Versantvoort, C. H.
Schuurhuis, G. J.
Pinedo, H. M.
Eekman, C. A.
Kuiper, C. M.
Lankelma, J.
Broxterman, H. J.
author_facet Versantvoort, C. H.
Schuurhuis, G. J.
Pinedo, H. M.
Eekman, C. A.
Kuiper, C. M.
Lankelma, J.
Broxterman, H. J.
author_sort Versantvoort, C. H.
collection PubMed
description In tumour cells the pharmacological basis for multidrug resistance (MDR) often appears to be a reduced cellular cytostatic drug accumulation caused by the drug efflux protein, P-glycoprotein (Pgp MDR), or by other drug transporters (non-Pgp MDR). Here we report the reversal of the decreased daunorubicin (DNR) accumulation in five non-Pgp MDR cell lines (GLC4/ADR, SW-1573/2R120, HT1080/DR4, MCF7/Mitox and HL60/ADR) by genistein. Genistein inhibited the enhanced DNR efflux in the GLC4/ADR cells. In these cells the decreased VP-16 accumulation was also reversed by genistein. Three other (iso)flavonoids biochanin A, apigenin and quercetin also increased the DNR accumulation in the GLC4/ADR cells. In contrast to the effects on non-Pgp MDR cells, 200 microM genistein did not increase the reduced DNR accumulation in three Pgp MDR cell lines (SW-1573/2R160, MCF7/DOX40 and KB8-5) or in the parental cell lines. In conclusion the use of genistein provides a means to probe non-Pgp related drug accumulation defects. IMAGES:
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spelling pubmed-19687122009-09-10 Genistein modulates the decreased drug accumulation in non-P-glycoprotein mediated multidrug resistant tumour cells. Versantvoort, C. H. Schuurhuis, G. J. Pinedo, H. M. Eekman, C. A. Kuiper, C. M. Lankelma, J. Broxterman, H. J. Br J Cancer Research Article In tumour cells the pharmacological basis for multidrug resistance (MDR) often appears to be a reduced cellular cytostatic drug accumulation caused by the drug efflux protein, P-glycoprotein (Pgp MDR), or by other drug transporters (non-Pgp MDR). Here we report the reversal of the decreased daunorubicin (DNR) accumulation in five non-Pgp MDR cell lines (GLC4/ADR, SW-1573/2R120, HT1080/DR4, MCF7/Mitox and HL60/ADR) by genistein. Genistein inhibited the enhanced DNR efflux in the GLC4/ADR cells. In these cells the decreased VP-16 accumulation was also reversed by genistein. Three other (iso)flavonoids biochanin A, apigenin and quercetin also increased the DNR accumulation in the GLC4/ADR cells. In contrast to the effects on non-Pgp MDR cells, 200 microM genistein did not increase the reduced DNR accumulation in three Pgp MDR cell lines (SW-1573/2R160, MCF7/DOX40 and KB8-5) or in the parental cell lines. In conclusion the use of genistein provides a means to probe non-Pgp related drug accumulation defects. IMAGES: Nature Publishing Group 1993-11 /pmc/articles/PMC1968712/ /pubmed/8105867 Text en https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Research Article
Versantvoort, C. H.
Schuurhuis, G. J.
Pinedo, H. M.
Eekman, C. A.
Kuiper, C. M.
Lankelma, J.
Broxterman, H. J.
Genistein modulates the decreased drug accumulation in non-P-glycoprotein mediated multidrug resistant tumour cells.
title Genistein modulates the decreased drug accumulation in non-P-glycoprotein mediated multidrug resistant tumour cells.
title_full Genistein modulates the decreased drug accumulation in non-P-glycoprotein mediated multidrug resistant tumour cells.
title_fullStr Genistein modulates the decreased drug accumulation in non-P-glycoprotein mediated multidrug resistant tumour cells.
title_full_unstemmed Genistein modulates the decreased drug accumulation in non-P-glycoprotein mediated multidrug resistant tumour cells.
title_short Genistein modulates the decreased drug accumulation in non-P-glycoprotein mediated multidrug resistant tumour cells.
title_sort genistein modulates the decreased drug accumulation in non-p-glycoprotein mediated multidrug resistant tumour cells.
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1968712/
https://www.ncbi.nlm.nih.gov/pubmed/8105867
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