Several anti-tumour drugs exert some of their cytotoxic effects by direct binding to DNA, thus inhibiting the transcription of certain genes. We analysed the influence of the anti-tumour antibiotic daunorubicin on the transcription of different genes in vivo using the budding yeast Saccharomyces cerevisiae. Daunorubicin only affected wild-type yeast strains at very high concentrations; however,...

The anthracyclines daunorubicin and doxorubicin were shown to induce apoptosis of hematopoietic cell lines. Here we report that they induce apoptosis of both nonactivated and phytohemagglutinin-activated human peripheral blood lymphocytes. Apoptosis demonstrated by surface expression of phosphatidylserine and typical nuclear alterations reached a maximum after 48 h of incubation with these agen...

The title new daunorubicin analogues have been prepared from methyl 4,6-O-benzylidene-2-C-methyl-alpha-D-ribo-hexopyranosid-3-ulose and daunomycinone. The antitumor activity of these compounds was very similar to that of daunorubicin.

The present study was performed to investigate the ability of the multidrug resistance protein (MRPI) to transport different cationic substrates in comparison with MDR1-P-glycoprotein (MDR1). Transport studies were performed with isolated membrane vesicles from in vitro selected multidrug resistant cell lines overexpressing MDR1 (A2780AD) or MRP1 (GLC4/Adr) and a MRP1-transfected cell line (S1(...

The activity of S9788, recently synthetized as a modulator of multidrug resistance (MDR), was compared with verapamil and cyclosporine A in normal sensitive and MDR K562 cell lines, then in samples from 33 patients with hematological malignancies, using flow cytometry with simultaneous detection of P-glycoprotein and determination of intracellular daunorubicin fluorescence. This technique was c...

DnrN, a protein essential for the transcription of the dnrI gene, which in turn activates transcription of the daunorubicin biosynthesis genes in Streptomyces peucetius, was overproduced in Escherichia coli and S. peucetius. The cell-free extract from E. coli was used to conduct DNA-binding assays. The results of gel mobility shift analysis showed that DnrN binds specifically to the dnrI promot...

PURPOSE The pipecolinate derivative VX-710 (biricodar; Incel) is a clinically applicable modulator of P-glycoprotein (Pgp) and multidrug resistance protein (MRP-1); we studied its activity against the third multidrug resistance (MDR)-associated drug efflux protein, breast cancer resistance protein (BCRP). EXPERIMENTAL DESIGN VX-710 modulation of uptake, retention, and cytotoxicity of mitoxant...

Introduction: Hematopoiesis is an on going process mammalian marrow system. A few cells from the nucleated cells of bone marrow are hematopoietic cells which include primary stem cells, precursor cells and progenitor cells. Primary stem cells and progenitor cells are able to produce colonies in culture medium (CFU-C) and irradiated mouse spleen (CFU-S). A hematopoietic cell is alive and act...

The effect of free and DNA-linked daunorubicin on the colony-forming ability of granulocyte-macrophage committed stem cells and spleen colony-forming cells (i.e., multipotent stem cells) from normal mice has been studied in vitro and in vivo. After incubation of bone marrow cells in short-term suspension cultures, both committed and multipotent stem cells were more sensitive to the free drug th...

We previously proposed that the adjacent dnrIJ genes represent a two-component regulatory system controlling daunorubicin biosynthesis in Streptomyces peucetius on the basis of the homology of the DnrI and DnrJ proteins to other response regulator proteins and the effect of a dnrI::aphII mutation. In the present paper we report the results of work with the dnrI::aphII mutant in complementation,...