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

A 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.

Saved in:
Bibliographic Details
Main Authors: Rubio, Sara, León, Francisco, Quintana, José, Cutler, Stephen, Estévez, Francisco
Other Authors: Ministerio de Ciencia e Innovación (España)
Format: artículo biblioteca
Published: Elsevier 2012-09
Subjects:Apoptosis, Caspases, Cell cycle, Cytotoxicity,
Online Access:http://hdl.handle.net/10261/193397
http://dx.doi.org/10.13039/501100004837
http://dx.doi.org/10.13039/501100000780
http://dx.doi.org/10.13039/501100003339
Tags: Add Tag
No Tags, Be the first to tag this record!