Quercetin enhances CD95- and TRAIL-induced apoptosis in leukemia cell lines.

CD95 (Fas/Apo-1) and TNF-related-apoptosis-inducing-ligand (TRAIL/Apo-2) are two of the six cellular receptors belonging to the TNF superfamily regulating the extrinsic apoptotic pathways after the interaction with their cognate ligand. Both CD95 and TRAIL are potential candidates to target apoptosis in malignant cells, even if their simple expression is not an essential feature for apoptosis sensitivity.1 In preclinical studies, the administration of soluble recombinant TRAIL (rTRAIL) or anti-CD95 agonistic antibody in experimental animals induced significant tumor regression without systemic toxicity.2, 3 This approach can be used to overcome chemotherapy resistance, for example, several types of leukemias; in this case, tumor resistance can be bypassed by a combined therapy including the activation of death receptors (DR; extrinsic pathway) and chemotherapy (intrinsic way).1 In this contest, a plethora of naturally occurring molecules with potential chemopreventive properties have been recently described.4 Among these, quercetin (3,3',4',5,7-pentahydroxyflavone), the major dietary flavonoid, abundantly present in a broad range of fruits and vegetables, has been intensively studied for its antioxidant, antiinflammatory, antiproliferative and, more recently, apoptotic effects in cell cultures and animal models.5