Resveratrol as Inducer of Apoptosis(Cell Death)

Piceatannol, a hydroxylated analog of the chemopreventive agent resveratrol, is a potent inducer of apoptosis in the lymphoma cell line BJAB and in primary, leukemic lymphoblasts

Author: Wieder T.[1], Prokop A.[2], Bagci B.[2], Essmann F.[1], Bernicke D.[3], Schulze-Osthoff K.[4], Dörken B.[1], Schmalz H-G.[3], Daniel P.T.[1], Henze G.[2], Correspondence: P T Daniel*

[1]Department of Hematology, Oncology and Tumor Immunology, University Medical Center Charite, Campus Berlin-Buch, Humboldt University of Berlin, Germany, [2]Department of Pediatric HematologyOncology, University Medical Center Charite, Campus Virchow, Humboldt University of Berlin, Germany, [3]Institute of Organic Chemistry, University of Koln, Germany, [4]Department of Immunology and Cell Biology, University of Munster, Germany, [*]Department of Hematology, Oncology, and Tumor Immunology, University Medical Center Charite, Campus Berlin-Buch, Humboldt University of Berlin, Lindenberger Weg 80, 13125 Berlin, Germany; Fax: 49 30 9417 1109

Abstract:

The stilbene phytochemicals resveratrol and piceatannol have been reported to possess substantial antitumorigenic and antileukemic activities, respectively. Although recent experimental data revealed the proapoptotic potency of resveratrol, the molecular mechanisms underlying the antileukemic activity have not yet been studied in detail.

In the present study, we show that resveratrol, as well as the hydroxylated analog piceatannol, are potent inducers of apoptotic cell death in BJAB Burkitt-like lymphoma cells with an ED50 concentration of 25 M.

Further experiments revealed that treatment of BJAB cells with both substances led to a concentration-dependent activation of caspase-3 and mitochondrial permeability transition. Using BJAB cells overexpressing a dominant-negative mutant of the Fas-associated death domain (FADD) adaptor protein to block death receptor-mediated apoptosis, we demonstrate that resveratrol- and piceatannol-induced cell death in these cells is independent of the CD95/Fas signaling pathway.

To explore the antileukemic properties of both compounds in more detail, we extended our study to primary, leukemic lymphoblasts.

Interestingly, piceatannol but not resveratrol is a very efficient inducer of apoptosis in this ex vivo assay with leukemic lymphoblasts of 21 patients suffering from childhood lymphoblastic leukemia (ALL).

Leukemia (2001) 15, 1735–1742.


Antileukemic  Activity of Resveratrol

J Nutrition, 6/02

Genistein Synergizes w/Fludarabine CLL & Apoptosis

Abstract # 3293 ASCO, 2004


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