In vitro antileukemic effect of a new anthracycline analogue, MEN 11079

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• 作者：Biscardi ; Monica ; Caporale ; Roberto ; Pagliai ; Gabriella ; Leoni ; Franco ; Bernabei ; Pietrantonio ; et. al.
• 关键词：Anthracycline analogues ; Acute myeloid leukemia ; Cytotoxicity ; Multidrug resistance ; P-glycoprotein ; MRP1
• 刊名：Leukemia Research
• 出版年：2003
• 出版时间：December, 2003
• 年：2003
• 卷：27
• 期：12
• 页码：1125-1134
• 全文大小：183 K

文摘

The biological activity of MEN 11079, a new daunorubucin analogue with a fluorine atom in C₈ 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 ID₅₀ values were also significantly different from each other (K-562: P=0.038; MNCs: P=0.003). Moreover, the range was 0.002–4.300μM for IDA and 0.002–0.670μM 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.