title: In vitro antileukemic effect of a new anthracycline analogue, MEN 11079.
abstract: The biological activity of MEN 11079, a new daunorubucin analogue with a fluorine atom in C(8) of ring A, was investigated in the human leukemic cell lines K-562 and in mononuclear cells (MNCs) of 40 patients with acute myeloid leukemia (AML) and the activity compared to two well-characterized anthracyclines, idarubicin (IDA) and doxorubicin (DOXO). IDA and MEN 11079 were more active than DOXO in cytotoxicity tests (WST-1 assay). IDA and MEN 11079 ID(50) values were also significantly different from each other (K-562: P=0.038; MNCs: P=0.003). Moreover, the range was 0.002-4.300 microM for IDA and 0.002-0.670 microM for MEN 11079, in the MNCs. Therefore, the latter appeared to assure a smaller variability of response in the AML cells. Apoptosis assays (performed using Annexin-V assay and propidium iodide) and cell cycle studies demonstrated that the MEN 11079 effective concentration was 10-fold lower than the DOXO and IDA ones. MDR (Pgp and MRP1 proteins), as measured by semiquantitative RT-PCR, cytofluorimetric and functional analysis of proteins, was similarly elicited by IDA and MEN 11079. In conclusion, the response of the cells to the new anthracycline indicates that there is greater cytotoxic activity of this molecule than IDA and DOXO. Its narrower ID(50) range may allow for a more predictable response in the clinical setting.
authors.affiliation: U.O. Hematology, Azienda Ospedaliera Careggi, University of Florence, Viale Morgagni 85, 50134 Florence, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Biscardi
authors.forename: Roberto
authors.initials: R
authors.lastname: Caporale
authors.forename: Gabriella
authors.initials: G
authors.lastname: Pagliai
authors.forename: Franco
authors.initials: F
authors.lastname: Leoni
authors.forename: Pietrantonio
authors.initials: P
authors.lastname: Bernabei
authors.forename: Valeria
authors.initials: V
authors.lastname: Santini
authors.forename: Stefania
authors.initials: S
authors.lastname: Ciolli
authors.forename: Alberto
authors.initials: A
authors.lastname: Grossi
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000208:Acute Disease; D000328:Adult; D000368:Aged; D017304:Annexin A5 / Q000378:metabolism; D018943:Anthracyclines / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000494:pharmacology; D020014:K562 Cells / Q000187:drug effects; D007951:Leukemia, Myeloid / Q000473:pathology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011419:Propidium / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D017304:Annexin A5; D018943:Anthracyclines; D000970:Antineoplastic Agents; C478372:MEN 11079; D011419:Propidium; D015255:Idarubicin; D003630:Daunorubicin