Discovery of a cobalt (III) salen complex that induces apoptosis in Burkitt like lymphoma and leukemia cells, overcoming multidrug resistance in vitro

[Display omitted] •A cobalt-salen complex, named MBR-60, showed apoptotic activity over the intrinsic pathway in leukemia and lymphoma cells.•The cobalt-free ligand did not affect tumor cells.•MBR-60 overcame multidrug resistances.•Outstanding synergistic effects of MBR-60 with daunorubicin and vinc...

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Veröffentlicht in:Bioorganic chemistry 2020-11, Vol.104, p.104193, Article 104193
Hauptverfasser: Hopff, Sina M., Onambele, Liliane A., Brandenburg, Marc, Berkessel, Albrecht, Prokop, Aram
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Sprache:eng
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Zusammenfassung:[Display omitted] •A cobalt-salen complex, named MBR-60, showed apoptotic activity over the intrinsic pathway in leukemia and lymphoma cells.•The cobalt-free ligand did not affect tumor cells.•MBR-60 overcame multidrug resistances.•Outstanding synergistic effects of MBR-60 with daunorubicin and vincristine were observed. A very small number of cobalt complexes is examined in oncology research. In this work, we investigate the cobalt (III) salen complex MBR-60 that turns out to be a promising anticancer drug. It induces apoptosis in Nalm6 leukemia and BJAB lymphoma cells and overcomes multidrug resistances by blocking the drug efflux pump P-glycoprotein. It further develops the apoptotic effects over the intrinsic pathway. An activation of caspase-3, caspase-8 and caspase-9 can be detected by western blot analysis. The independence of CD95 is shown by similar apoptotic inductions in BJAB and BJAB FADDdn cells. MBR-60 displays synergistic effects with daunorubicin and vincristine and has a selectivity to tumor cells. In comparison to the apoptotic effects of MBR-60 in BJAB lymphoma cells, the cobalt-free ligand 5 does not influence these cells. The research highlights that a cobalt complex has a therapeutic potential for cancer treating with a focus on drug-resistant tumors.
ISSN:0045-2068
1090-2120
DOI:10.1016/j.bioorg.2020.104193