title: Biochemical effects of piceatannol in human HL-60 promyelocytic leukemia cells--synergism with Ara-C.
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.
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, General Hospital of Vienna, A-1090 Vienna, Austria.
authors.forename: Monika
authors.initials: M
authors.lastname: Fritzer-Szekeres
authors.forename: Ivo
authors.initials: I
authors.lastname: Savinc
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Horvath
authors.forename: Philipp
authors.initials: P
authors.lastname: Saiko
authors.forename: Michael
authors.initials: M
authors.lastname: Pemberger
authors.forename: Geraldine
authors.initials: G
authors.lastname: Graser
authors.forename: Astrid
authors.initials: A
authors.lastname: Bernhaus
authors.forename: Maria
authors.initials: M
authors.lastname: Ozsvar-Kozma
authors.forename: Michael
authors.initials: M
authors.lastname: Grusch
authors.forename: Walter
authors.initials: W
authors.lastname: Jaeger
authors.forename: Thomas
authors.initials: T
authors.lastname: Szekeres
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000494:pharmacology; D002453:Cell Cycle; D003561:Cytarabine / Q000008:administration & dosage*; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D008956:Models, Chemical; D011419:Propidium / Q000494:pharmacology; D012264:Ribonucleotide Reductases / Q000737:chemistry; D013267:Stilbenes / Q000008:administration & dosage*; D013997:Time Factors
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D013267:Stilbenes; D003561:Cytarabine; D011419:Propidium; C041525:3,3',4,5'-tetrahydroxystilbene; D012264:Ribonucleotide Reductases