Induction of DNA damage, inhibition of DNA synthesis and suppression of c-myc expression by the anthracycline analog, idarubicin (4-demethoxy-daunorubicin) in the MCF-7 breast tumor cell line

Cancer Chemotherapy and Pharmacology
D A GewirtzF A Fornari

Abstract

Studies were designed to elucidate the basis for the antiproliferative activity of the anthracycline antibiotic, idarubicin (4-demethoxy-daunorubicin) in MCF-7 breast tumor cells. Growth inhibition was evaluated using the MTT tetrazolium dye assay, induction of DNA strand breaks was determined by alkaline elution, inhibition of DNA synthesis was assessed by measuring the incorporation of labelled thymidine into DNA, modulation of the expression of the c-myc oncogene was determined by Northern blotting and the induction of apoptosis was evaluated by alkaline unwinding, static field gel electrophoresis, terminal end labelling and assessment of cell morphology. MCF-7 cells were relatively sensitive to idarubicin, with an IC50 value for growth inhibition of approximately 0.01 microM. While DNA strand breakage was not evident below a concentration of 0.1 microM idarubicin, where growth inhibition exceeded 70%, both the inhibition of DNA synthesis and suppression of c-myc expression closely paralleled the profile of antiproliferative activity for idarubicin. Finally, while exposure to idarubicin resulted in a substantial loss of viable cells within 48-72 h, there was no morphological evidence of apoptotic body formation. The absence ...Continue Reading

Citations

Apr 19, 2002·Biochemical Pharmacology·Silvia VillamarínJosé Portugal
Nov 20, 2001·Molecular and Cellular Biology·I CollinsD Levens
Apr 15, 2009·Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia·Katerina BouchalovaMarian Hajduch
Jun 5, 2013·International Journal of Biological Macromolecules·Sonika Charak, Ranjana Mehrotra
May 30, 2019·Acta Pharmacologica Sinica·Fu-Lai ZhouMing-Wei Wang
Mar 1, 2019·Chemical Research in Toxicology·Shangwei ZhongHailin Wang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis