In the present paper we show that the overexpression of the NL1Tc protein, encoded by the L1Tc non-LTR retrotransposon from Trypanosoma cruzi, led to a reduction of about 60% of DNA damage caused by daunorubicin treatment. This repair effect is not observed in transfected parasites overexpressing the NL1Tc mutated in the aspartic acid located in the active site of the enzyme. In addition, NL1Tc...

Daunorubicin transport was compared in P388 murine leukemia and in P388/Adramycin (ADR), an anthracycline-resistant subline. We can demonstrate an energy-dependent outward transport system in P388/ADR which limits drug accumulation. Although no calcium requirement for the outward transport process could be shown, several calcium antagonists inhibited outward transport of daunorubicin in P388/AD...

Using a cell-based reporter gene assay, we screened a library of drugs in clinical use and identified the anthracycline chemotherapeutic agents doxorubicin and daunorubicin as potent inhibitors of hypoxia-inducible factor 1 (HIF-1)-mediated gene transcription. These drugs inhibited HIF-1 by blocking its binding to DNA. Daily administration of doxorubicin or daunorubicin potently inhibited the t...

Scar formation and fibrosis are the most common causes of ultimate glaucoma filtration surgery failure. The authors used Coulter counter, hexosaminidase, and 3H-thymidine assays to evaluate the effects of mithramycin, mitomycin, daunorubicin, and bleomycin on human subconjunctival fibroblast growth in tissue culture. Fifty percent inhibitory doses (ID50) for each drug on different days of incub...

Independent lines of Chinese hamster ovary cells resistant to the antineoplastic drug, daunorubicin, were obtained by clonal isolation in increasing drug concentrations. A single daunorubicin-resistant phenotype typified by reduced cellular drug accumulation was observed. These mutants displayed a complex phenotype of resistance to a variety of unrelated drugs. Such properties are similar to th...

In October 2011, the US Food and Drug Administration (FDA) announced the end of the cytarabine shortage. Cytarabine is the key chemotherapy drug for the management of leukemia in children and adults, particularly acute myeloid leukemia, and the announcement by the FDA of an end to this 11-month crisis was good news. However, in July 2011, we started experiencing shortages of daunorubicin, anoth...

The anthracyclines doxorubicin and daunorubicin are used in the treatment of various human and canine cancers, but anthracyclinerelated cardiotoxicity limits their clinical utility. The formation of anthracycline C-13 alcohol metabolites (e.g., doxorubicinol and daunorubicinol) contributes to the development of anthracyclinerelated cardiotoxicity. The enzymes responsible for the synthesis of an...

BACKGROUND The involvement of protein kinase CK2 in sustaining cancer cell survival could have implications also in the resistance to conventional and unconventional therapies. Moreover, CK2 role in blood tumors is rapidly emerging and this kinase has been recognized as a potential therapeutic target. Phase I clinical trials with the oral small ATP-competitive CK2 inhibitor CX-4945 are currentl...

Fu D, Roufogalis BD. Actin disruption inhibits endosomal traffic of P-glycoprotein-EGFP and resistance to daunorubicin accumulation. Am J Physiol Cell Physiol 292: C1543–C1552, 2007. First published November 22, 2006; doi:10.1152/ajpcell.00068.2006.—Intracellular traffic of human P-glycoprotein (P-gp), a membrane transporter responsible for multidrug resistance in cancer chemotherapy, was inves...

BACKGROUND Recently, we have shown that dexrazoxane (ICRF-187) is an effective antidote against accidental extravasation of anthracyclines. Thus, it inhibits the lesions induced by subcutaneous (s.c.) daunorubicin, idarubicin, and doxorubicin in mice and has proven to be successful clinically as well. Dexrazoxane is a potent metal ion chelator as well as being a catalytic inhibitor of DNA topoi...