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The role of methoxymorpholino anthracycline and cyanomorpholino anthracycline in a sensitive small-cell lung-cancer cell line and its multidrug-resistant butP-glycoprotein-negative and cisplatin-resistant counterparts

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  • Morpholino Anthracyclines, MRP, Cisplatin Resistance
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Abstract

The cytotoxic action of two morpholino anthracyclines, methoxymorpholino anthracycline (MRA-MT, FCE 23 762) and cyanomorpholino anthracycline (MRA-CN), was compared with the cytotoxicity of doxorubicin (DOX), the topoisomerase II inhibitor etoposide (VP-16), the topoisomerase I inhibitor camptothecin, methotrexate, and cisplatin in GLC4, a human small-cell lung-cancer cell line, in GLC4-Adr, its P-glycoprotein (Pgp)-negative, multidrug-resistant (MDR; 100-fold DOX-resistant) subline with overexpression of the MDR-associated protein (MRP) and a lowered topoisomerase II activity, and in GLC4-CDDP, its cisplatin-resistant subline. GLC4-Adr was about 2-fold cross-resistant for the morpholino anthracyclines and GLC4-CDDP was, relative to GLC4, more resistant for the morpholino anthracyclines than for DOX. Overall, MRA-CN was about 2.5-fold more cytotoxic than MRA-MT. The cytotoxicity profile of the morpholino anthracyclines in these cell lines mimicked that of camptothecin.

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Authors and Affiliations

  1. Department of Internal Medicine, Division of Medical Oncology, University Hospital, Oostersingel 59, 9713 EZ, Groningen, The Netherlands

    Winette T. A. van der Graaf, Nanno H. Mulder, Coby Meijer & Elisabeth G. E. de Vries

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  1. Winette T. A. van der Graaf
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  2. Nanno H. Mulder
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  3. Coby Meijer
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  4. Elisabeth G. E. de Vries
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van der Graaf, W.T.A., Mulder, N.H., Meijer, C. et al. The role of methoxymorpholino anthracycline and cyanomorpholino anthracycline in a sensitive small-cell lung-cancer cell line and its multidrug-resistant butP-glycoprotein-negative and cisplatin-resistant counterparts. Cancer Chemother. Pharmacol. 35, 345–348 (1995). https://doi.org/10.1007/BF00689457

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  • DOI: https://doi.org/10.1007/BF00689457

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