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.
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 microM. 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).
Wieder
T
T
Department of Hematology, Oncology and Tumor Immunology, University Medical Center Charité, Humboldt University of Berlin, Germany.
Prokop
A
A
Bagci
B
B
Essmann
F
F
Bernicke
D
D
Schulze-Osthoff
K
K
Dörken
B
B
Schmalz
H G
HG
Daniel
P T
PT
Henze
G
G
D000293:Adolescent; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002051:Burkitt Lymphoma / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002467:Cell Nucleus / Q000648:ultrastructure; D002648:Child; D002675:Child, Preschool; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007223:Infant; D007945:Leukemia, Lymphoid / Q000473:pathology*; D008297:Male; D008564:Membrane Potentials; D008928:Mitochondria / Q000502:physiology; D000077185:Resveratrol; D015398:Signal Transduction; D013267:Stilbenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000378:metabolism
D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D013267:Stilbenes; D019014:fas Receptor; C041525:3,3',4,5'-tetrahydroxystilbene; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D000077185:Resveratrol