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Title

Cell death triggered by synthetic flavonoids in human leukemia cells is amplified by the inhibition of extracellular signal-regulated kinase signaling

AuthorsRubio, Sara; León, Francisco ; Quintana, José; Cutler, Stephen; Estévez, Francisco
KeywordsApoptosis
Caspases
Cell cycle
Cytotoxicity
Issue DateSep-2012
PublisherElsevier
CitationEuropean Journal of Medicinal Chemistry 55: 284-296 (2012)
AbstractA new class of methyl esters of flavonoids, with different substituents on the B ring were synthesized and evaluated for their antiproliferative activity against the human leukemia cell line HL-60. The presence of either a methyl group (1f) or a chlorine atom (1o) at position 2′ of the B ring played an important role in affecting antiproliferative activity. The cytotoxic effects of these compounds were accompanied by the concentration- and time-dependent appearance of DNA- and nuclear-fragmentation, increase in the percentage of sub-G 1 cells, and processing of multiple caspases and poly(ADP-ribose)polymerase cleavage. Pretreatment of cells with the specific mitogen-activated extracellular kinases (MEK) 1/2 inhibitor PD98059, together with 1f and 1o, resulted in an important enhancement of cell death, which might have clinical implications for the use of both compounds in combination with MEK 1/2 inhibitors as potential therapeutic agents.
Publisher version (URL)https://doi.org/10.1016/j.ejmech.2012.07.028
URIhttp://hdl.handle.net/10261/193397
DOIhttp://dx.doi.org/10.1016/j.ejmech.2012.07.028
Identifiersdoi: 10.1016/j.ejmech.2012.07.028
issn: 0223-5234
e-issn: 1768-3254
Appears in Collections:(IPNA) Artículos
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