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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.

Resveratrol (3,4',5,-trihydroxystilbene, RV), an ingredient of wine, exhibits a broad spectrum of antiproliferative effects against human cancer cells. In order to develop a derivative with comparable effects, we modified the molecule by introducing additional methoxyl groups. The resulting novel RV analog, N-hydroxy-N'-(3,4,5-trimethoxyphenyl)-3,4,5-trimethoxybenzamidine (KITC), was investigated in HL-60 human promyelocytic leukemia cells. The induction of apoptosis was determined employing a specific Hoechst/propidium iodide double staining method and cell cycle distribution was evaluated by FACS. KITC's influence on the concentration of deoxyribonucleoside triphosphates, the products of ribonucleotide reductase (RR), was determined using the HPLC method. In addition, we analyzed the effects of KITC treatment on the incorporation of 14C-cytidine into the DNA of tumor cells in order to quantify the loss of RR in situ activity. To reveal a potential value of KITC for supporting conventional chemotherapy, we also examined whether a combination of KITC with arabinofuranosylcytosine (Ara-C) could yield synergistic growth inhibitory effects. KITC caused a dose-dependent induction of apoptosis, whereas no remarkable changes of the cell cycle distribution were observed. Incubation with KITC resulted in a significant depletion of intracellular dTTP and dATP pools and was also found to remarkably reduce the in situ activity of RR, the key enzyme of de novo DNA synthesis. In addition, KITC exhibited synergistic combination effects when applied sequentially with Ara-C. Due to these promising results, KITC deserves further preclinical and in vivo testing.

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, weidentified additional biochemical targets of PCA in humanHL-60 promyelocytic leukemia cells. Incubation with PCAled to a significant proportion of apoptotic cells and causedan arrest in the G2-M phase of the cell cycle. PCA depletedintracellular dCTP and dGTP pools, and inhibited the incor-poration of 14 C-labeled cytidine into DNA. PCA significantlyabolished all NTP pools, and sequential treatment with PCAand Ara-C yielded synergistic growth inhibitory effects becauseof remarkably increased Ara-CTP formation after PCA pre-incubation. Due to these promising results, PCA may supportconventional chemotherapy of human malignancies andtherefore, deserves further preclinical and in vivo testing. Introduction Piceatannol (3,3',4,5'-tetrahydroxy- trans -stilbene; PCA),is a natural product present in various berries, plants andgrapes as well as in wine. It can be metabolized by cytochromeP450 isoenzymes from resveratrol (3,4',5-trihydroxy