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 |
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Format: | Artikel |
Sprache: | eng |
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•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. |
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ISSN: | 0045-2068 1090-2120 |
DOI: | 10.1016/j.bioorg.2020.104193 |