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

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.

authors

van der Graaf WT,Mulder NH,Meijer C,de Vries EG

doi

10.1007/BF00689457

subject

Has Abstract

pub_date

1995-01-01 00:00:00

pages

345-8

issue

4

eissn

0344-5704

issn

1432-0843

journal_volume

35

pub_type

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