Biochemical effects of piceatannol in human HL-60 promyelocytic leukemia cells--synergism with Ara-C |
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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 |
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Affiliation: | Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, General Hospital of Vienna, A-1090 Vienna, Austria. |
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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. |
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