A comparative analysis of the sensitivity of multidrug resistant (MDR) and non-MDR cells to different anthracycline derivatives.
Because of the fact that tumor cell sensitivity to cytotoxic agents may play a major role in cancer treatment, and several anthracyclines are widely used for first-line treatment of leukemia, lymphoma and other tumors, and since the overexpression of the mdr-1 gene-coded 170 Kd glycoprotein (P170) decreases cell sensitivity to anthracyclines, we investigated the relationship between P170 overexpression and the cytotoxicity of two classic anthracyclines (Daunorubicin or DNR and Doxorubicin or DX) and two lipophilic anthracycline derivatives (Idarubicin or IDA and Iododoxorubicin or IDX). For these purposes, we used multidrug resistant (MDR) and non-MDR tumor and leukemia cell lines and the MTT-microcultured tetrazolium colorimetric assay. We showed that mdr-1 gene overexpression was strongly associated with the development of a high level of resistance to DNR and DX, but not to the derivatives IDA and IDX. These data suggest that more lipophilic anthracycline derivatives may also be active in MDR cell systems.
Michieli
M
M
Section of Hematology, University of Udine School of Medicine, Italy.
Michelutti
A
A
Damiani
D
D
Pipan
C
C
Raspadori
D
D
Lauria
F
F
Baccarani
M
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000473:pathology; D003630:Daunorubicin / Q000494:pharmacology; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics; D004354:Drug Screening Assays, Antitumor; D015870:Gene Expression; D006801:Humans; D015255:Idarubicin / Q000494:pharmacology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000473:pathology; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D008562:Membrane Glycoproteins; C053044:4'-deoxy-4'-iododoxorubicin; D004317:Doxorubicin; D015255:Idarubicin; D003630:Daunorubicin