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Antiproliferative activity and apoptosis induction by 3′,4′-dibenzyloxyflavonol on human leukemia cells

AuthorsSaid, Mercedes; Brouard, Ignacio CSIC ORCID ; Quintana, José; Estévez, Francisco
Cell cycle
Issue Date25-Apr-2017
CitationChemico-Biological Interactions 268: 13-23 (2017)
AbstractIn this study, we investigated the effects of synthetic 3′,4′-dibenzyloxyflavonol on viabilities of eight human tumor cells. It was cytotoxic against leukemia cells (HL-60, U-937, MOLT-3, K-562, NALM-6, Raji), with significant effects against P-glycoprotein-overexpressing K-562/ADR and Bcl-2-overexpressing U-937/Bcl-2 cells, but had no significant cytotoxic effects against quiescent or proliferating human peripheral blood mononuclear cells. The IC50 value for the leukemia HL-60 cells was 0.8 ± 0.1 μM. This indicates a 60–fold greater toxicity than the naturally occurring flavonol quercetin. Synthetic 3′,4′-dibenzyloxyflavonol induced S phase cell cycle arrest and was a potent apoptotic inducer in human leukemia cells. Cell death was (i) mediated by the activation and the cleavage of initiator and executioner caspases; (ii) prevented by the pan-caspase inhibitor z-VAD-fmk; (iii) associated with the release of cytochrome c and with the phosphorylation of members of the mitogen activated protein kinases including p38MAPK, JNK/SAPK and ERK, and (iv) independent of the generation of reactive oxygen species. The synthetic 3′,4′-dibenzyloxyflavonol is a potent cytotoxic compound against several human leukemia cells and might be useful in the development of new strategies in the fight against cancer.
Publisher version (URL)https://doi.org/10.1016/j.cbi.2017.02.010
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