Biochemical effects of piceatannol in human HL-60 promyelocytic leukemia cells--synergism with Ara-C.
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.
Fritzer-Szekeres
Monika
M
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, General Hospital of Vienna, A-1090 Vienna, Austria.
Savinc
Ivo
I
Horvath
Zsuzsanna
Z
Saiko
Philipp
P
Pemberger
Michael
M
Graser
Geraldine
G
Bernhaus
Astrid
A
Ozsvar-Kozma
Maria
M
Grusch
Michael
M
Jaeger
Walter
W
Szekeres
Thomas
T
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
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D013267:Stilbenes; D003561:Cytarabine; D011419:Propidium; C041525:3,3',4,5'-tetrahydroxystilbene; D012264:Ribonucleotide Reductases