Synthesis and effects on cell viability of flavonols and 3-methyl ether derivatives on human leukemia cells

• 4′-Bromoflavonol as apoptotic inducer in leukemia cells.
• Cell death was associated with the activation of multiple caspases.
• The intrinsic and the extrinsic pathways are involved in the mechanism of action.
• Death receptors are up-regulated and TRAIL enhances apoptotic cell death.

Flavonoids are polyphenolic compounds which display an array of biological activities and are considered potential antitumor agents. Here we evaluated the antiproliferative activity of selected synthetic flavonoids against human leukemia cell lines. We found that 4′-bromoflavonol (flavonol 3) was the most potent. This compound inhibited proliferation in a concentration-dependent manner, induced apoptosis and blocked cell cycle progression at the S phase. Cell death was found to be associated with the cleavage and activation of multiple caspases, the activation of the mitogen-activated protein kinase pathway and the up-regulation of two death receptors (death receptor 4 and death receptor 5) for tumor necrosis factor-related apoptosis-inducing ligand. Moreover, combined treatments using 4′-bromoflavonol and TRAIL led to an increased cytotoxicity compared to single treatments. These results provide a basis for further exploring the potential applications of this combination for the treatment of cancer.

Figure optionsDownload as PowerPoint slide