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Transcriptional down-regulation of c-myc expression in an erythroleukemic cell line, K562, and its doxorubicin-resistant variant by two topoisomerase II inhibitors, doxorubicin and amsacrine

Abstract : We have evaluated the effect of two topoisomerase II (Topo II) poisons, amsacrine and doxorubicin, on the expression of the c-myc oncogene, both at the mRNA and protein levels, in the leukemia cell line, K562, and its doxorubicin-resistant counterpart, K562 DoxR. We report in this study a concentration-dependent decrease in c-myc mRNA levels upon exposure of both cell lines to amsacrine and doxorubicin, with a more pronounced effect for amsacrine in the resistant line. In either case, c-myc down-regulation closely paralleled the drug-induced growth inhibition. We have also used the technique of PCR stop-assay to detect the occurrence of DNA breaks within the P2 promoter of the c-myc gene. We have shown that Topo II-mediated breaks induced by amsacrine are probably responsible for the down-regulation of c-myc in the resistant line. In addition, amsacrine induced apoptosis only in the resistant line while doxorubicin did not induce apoptosis in any cell line. These results suggest that c-myc is not involved in the resistance of K562 DoxR cells, but can induce the apoptosis pathway in these cells, while no drug-induced apoptosis could be detected in the sensitive line.
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https://www.hal.inserm.fr/inserm-02438227
Contributor : Philippe Pourquier <>
Submitted on : Tuesday, January 14, 2020 - 10:32:15 AM
Last modification on : Wednesday, September 16, 2020 - 4:05:55 PM

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Audrey Clary, Annick Larrue, Philippe Pourquier, Jacques Robert. Transcriptional down-regulation of c-myc expression in an erythroleukemic cell line, K562, and its doxorubicin-resistant variant by two topoisomerase II inhibitors, doxorubicin and amsacrine. Anti-Cancer Drugs, Lippincott, Williams & Wilkins, 1998, 9 (3), pp.245-254. ⟨10.1097/00001813-199803000-00007⟩. ⟨inserm-02438227⟩

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