Kinase Assay: |
Mol. Carcinogen., 2010, 49(5): 464-75. | 5,7,3'-trihydroxy-3,4'-dimethoxyflavone-induced cell death in human leukemia cells is dependent on caspases and activates the MAPK pathway.[Pubmed: 20175127] | Flavonoids are polyphenolic compounds which display a vast array of biological activities and are promising anticancer agents. METHODS AND RESULTS: In this study we investigated the effect of 5,7,3'-trihydroxy-3,4'-dimethoxyflavone (Quercetin 3,4'-dimethyl ether,THDF) on viability of nine human tumor cell lines and found that it was highly cytotoxic against leukemia cells. THDF induced G(2)-M phase cell-cycle arrest and apoptosis through a caspase-dependent mechanism involving cytochrome c release, processing of multiple caspases (caspase-3, -6, -7, and -9) and cleavage of poly(ADP-ribose) polymerase. Overexpression of the protective mitochondrial proteins Bcl-2 and Bcl-x(L) conferred partial resistance to THDF-induced apoptosis.
CONCLUSIONS:
This flavonoid induced the phosphorylation of members of the mitogen-activated protein kinases (MAPKs) family and cell death was attenuated by inhibition of c-jun N-terminal kinases/stress-activated protein kinases (JNK/SAPK) and of extracellular signal-regulated kinases (ERK) 1/2. |
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