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

Leukemia volume 21, pages 1130–1133 (2007)Cite this article

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

Jurkat cell line was reported to be very responsive to both TRAIL and anti-CD95 inducers, and similarly to HPB-ALL, Jurkat cells are sensitive to the enhancement activity of anti-CD95 and quercetin. When quercetin was associated with anti-CD95 or rTRAIL, caspase 3 activity increased 3- and 2.5-fold, respectively, compared to the treatment with DRs alone (Table 1). The enhancing effect of TRAIL and quercetin on Jurkat cells was also confirmed by cell viability (Table 1) and PARP degradation (Figure 1b). These results demonstrate that quercetin enhanced DR-dependent apoptosis in Jurkat cells, a lymphoid cell line partially sensitive to CD95 and TRAIL induction.

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Acknowledgements

We thank G Iacomino and I Tedesco from the BJ-Lab for the helpful participation and discussion in the preparation of the present work. This study was supported by grant, ‘Benefits and risks of dietary antioxidants in preventing chronic and degenerative pathologies’ from Italian Ministry of Health (Ricerca Finalizzata 2002, Roma, Italy) and, partially, by Centro Regionale di Competenza Produzioni Agroalimentari (Regione Campania).

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  1. Institute of Food Sciences, National Research Council, Avellino, Italy

    M Russo, P Nigro, R Rosiello, R D'Arienzo & G L Russo

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Correspondence to G L Russo.

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Russo, M., Nigro, P., Rosiello, R. et al. Quercetin enhances CD95- and TRAIL-induced apoptosis in leukemia cell lines. Leukemia 21, 1130–1133 (2007). https://doi.org/10.1038/sj.leu.2404610

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