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P388 leukaemia cells resistant to the anthracycline menogaril lack multidrug resistant phenotype.

Menogaril is an anthracycline presently in Phase II clinical trials. Menogaril-resistant mouse leukaemia P388 cells were developed in vitro by 4 months of exposure to step-wise increasing concentrations of menogaril after which resistant cells (P388/MEN) were cloned in 320 ng ml-1 menogaril. P388/ME...

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Autores principales: Badiner, G. J., Moy, B. C., Smith, K. S., Tarpley, W. G., Groppi, V. E., Bhuyan, B. K.
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 1990
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1971454/
https://www.ncbi.nlm.nih.gov/pubmed/2145026
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author Badiner, G. J.
Moy, B. C.
Smith, K. S.
Tarpley, W. G.
Groppi, V. E.
Bhuyan, B. K.
author_facet Badiner, G. J.
Moy, B. C.
Smith, K. S.
Tarpley, W. G.
Groppi, V. E.
Bhuyan, B. K.
author_sort Badiner, G. J.
collection PubMed
description Menogaril is an anthracycline presently in Phase II clinical trials. Menogaril-resistant mouse leukaemia P388 cells were developed in vitro by 4 months of exposure to step-wise increasing concentrations of menogaril after which resistant cells (P388/MEN) were cloned in 320 ng ml-1 menogaril. P388/MEN cells were 40-fold more resistant to menogaril in vitro compared to P388/O and were also resistant in vivo. Resistance to menogaril was stable for at least 2 months in the absence of the drug. The results indicate that P388/MEN, although resistant to an anthracycline, did not display the typical multidrug resistant phenotype. It was not cross-resistant to several structurally unrelated drugs such as actinomycin D, cisplatin, or vinblastine, but it was cross-resistant to the anthracycline, adriamycin. Uptake and efflux of menogaril was similar in sensitive and resistant cell lines. Also, resistance was not reversed by verapamil. No major karyotypic difference was noted between P388/O and P388/MEN. There was no significant amplification or overexpression of the mdr gene in P388/MEN compared to P388/O. In contrast to P388/MEN, P388 cells resistant to adriamycin displayed the typical multidrug resistant phenotype. Glutathione content of P388/MEN cells was similar to that of P388/O and depletion of glutathione did not potentiate menogaril cytotoxicity. Therefore, we conclude that glutathione is not likely to be involved in menogaril resistance to P388/MEN cells. IMAGES:
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spelling pubmed-19714542009-09-10 P388 leukaemia cells resistant to the anthracycline menogaril lack multidrug resistant phenotype. Badiner, G. J. Moy, B. C. Smith, K. S. Tarpley, W. G. Groppi, V. E. Bhuyan, B. K. Br J Cancer Research Article Menogaril is an anthracycline presently in Phase II clinical trials. Menogaril-resistant mouse leukaemia P388 cells were developed in vitro by 4 months of exposure to step-wise increasing concentrations of menogaril after which resistant cells (P388/MEN) were cloned in 320 ng ml-1 menogaril. P388/MEN cells were 40-fold more resistant to menogaril in vitro compared to P388/O and were also resistant in vivo. Resistance to menogaril was stable for at least 2 months in the absence of the drug. The results indicate that P388/MEN, although resistant to an anthracycline, did not display the typical multidrug resistant phenotype. It was not cross-resistant to several structurally unrelated drugs such as actinomycin D, cisplatin, or vinblastine, but it was cross-resistant to the anthracycline, adriamycin. Uptake and efflux of menogaril was similar in sensitive and resistant cell lines. Also, resistance was not reversed by verapamil. No major karyotypic difference was noted between P388/O and P388/MEN. There was no significant amplification or overexpression of the mdr gene in P388/MEN compared to P388/O. In contrast to P388/MEN, P388 cells resistant to adriamycin displayed the typical multidrug resistant phenotype. Glutathione content of P388/MEN cells was similar to that of P388/O and depletion of glutathione did not potentiate menogaril cytotoxicity. Therefore, we conclude that glutathione is not likely to be involved in menogaril resistance to P388/MEN cells. IMAGES: Nature Publishing Group 1990-09 /pmc/articles/PMC1971454/ /pubmed/2145026 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
Badiner, G. J.
Moy, B. C.
Smith, K. S.
Tarpley, W. G.
Groppi, V. E.
Bhuyan, B. K.
P388 leukaemia cells resistant to the anthracycline menogaril lack multidrug resistant phenotype.
title P388 leukaemia cells resistant to the anthracycline menogaril lack multidrug resistant phenotype.
title_full P388 leukaemia cells resistant to the anthracycline menogaril lack multidrug resistant phenotype.
title_fullStr P388 leukaemia cells resistant to the anthracycline menogaril lack multidrug resistant phenotype.
title_full_unstemmed P388 leukaemia cells resistant to the anthracycline menogaril lack multidrug resistant phenotype.
title_short P388 leukaemia cells resistant to the anthracycline menogaril lack multidrug resistant phenotype.
title_sort p388 leukaemia cells resistant to the anthracycline menogaril lack multidrug resistant phenotype.
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1971454/
https://www.ncbi.nlm.nih.gov/pubmed/2145026
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