Resveratrol, an ingredient of wine, acts synergistically with Ara-C and tiazofurin in HL-60 human promyelocytic leukemia cells.
Resveratrol (RV), a naturally occurring stilbene derivative, is a potent free radical scavenger causing a number of biochemical and antineoplastic effects. It was shown to induce differentiation and apoptosis in leukemia cells and was also identified as an inhibitor of ribonucleotide reductase (RR), a key enzyme of DNA synthesis. In this study, we report about the biochemical effects of RV in HL-60 human promyelocytic leukemia cells. RV effectively inhibited in situ RR activity. Furthermore, incubation of HL-60 cells with RV significantly decreased intracellular dCTP, dTTP, dATP and dGTP concentrations. In growth inhibition and clonogenic assays, RV acted synergistically with both Ara-C and tiazofurin in HL-60 cells. We conclude that RV could become a viable candidate as one compound in the combination chemotherapy of leukemia and therefore deserves further in vitro and in vivo testing.
Horvath
Z
Z
Clinical Institute of Medical and Chemical Laboratory Diagnostics, General Hospital of Vienna, Medical University of Vienna, Vienna, Austria. zsuzsanna.Horvath@gmx.at
Saiko
P
P
Illmer
C
C
Madlener
S
S
Hoechtl
T
T
Bauer
W
W
Erker
T
T
Jaeger
W
W
Fritzer-Szekeres
M
M
Szekeres
T
T
D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D017209:Apoptosis; D049109:Cell Proliferation / Q000187:drug effects; D003561:Cytarabine / Q000008:administration & dosage*; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D016166:Free Radical Scavengers; D005609:Free Radicals; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D000077185:Resveratrol; D012254:Ribavirin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013267:Stilbenes / Q000008:administration & dosage*
D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D016166:Free Radical Scavengers; D005609:Free Radicals; D013267:Stilbenes; D003561:Cytarabine; D012254:Ribavirin; D000077185:Resveratrol; C033706:tiazofurin