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Biochemical effects of piceatannol in human HL-60 promyelocytic leukemia cells--synergism with Ara-C
Authors:Fritzer-Szekeres Monika  Savinc Ivo  Horvath Zsuzsanna  Saiko Philipp  Pemberger Michael  Graser Geraldine  Bernhaus Astrid  Ozsvar-Kozma Maria  Grusch Michael  Jaeger Walter  Szekeres Thomas
Affiliation:Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, General Hospital of Vienna, A-1090 Vienna, Austria.
Abstract:
Piceatannol (3,3',4,5'-tetrahydroxy-trans-stilbene; PCA) is a naturally occurring metabolite of resveratrol (3,4',5-trihydroxy-trans-stilbene; RV). In this study, we identified additional biochemical targets of PCA in human HL-60 promyelocytic leukemia cells. Incubation with PCA led to a significant proportion of apoptotic cells and caused an arrest in the G2-M phase of the cell cycle. PCA depleted intracellular dCTP and dGTP pools, and inhibited the incorporation of 14C-labeled cytidine into DNA. PCA significantly abolished all NTP pools, and sequential treatment with PCA and Ara-C yielded synergistic growth inhibitory effects because of remarkably increased Ara-CTP formation after PCA preincubation. Due to these promising results, PCA may support conventional chemotherapy of human malignancies and therefore, deserves further preclinical and in vivo testing.
Keywords:
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