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.

Cytotoxic and apoptotic effects of novel heterodinucleoside phosphates consisting of 5-fluorodeoxyuridine and Ara-C in human cancer cell lines.

In search for possible alternatives in the treatment of human malignancies we investigated several new heterodinucleoside phosphates consisting of 5-Fluorodeoxyuridine (5-FdUrd) and Arabinofuranosylcytosine (Ara-C). We show that all dimers tested inhibited the number of colonies of CCL228, CCL227, 5-FU resistant CCL227 and HT-29 human colon tumor cells with IC50 values ranging from 0.65 to 1 nM. Dimer # 2 inhibited the number of sensitive and Ara-C resistant H9 human lymphoma cells with IC50 values ranging from 200 to 230 nM. Since no significant difference in the cytotoxicity of the dimers could be observed between sensitive and resistant cells, these compounds might be used in the treatment of 5-FU and Ara-C resistant tumors.