The effects of resveratrol on cell cycle, apoptosis, and NF-kB activation

Abstract

Purpose: To study the effect of resveratrol, a putative chemopreventive phytoalexin, on DNA synthesis, cell cycle, apoptosis, and the possible involvement of the transcription factor NF-kB. Results: Resveratrol induces a complex dose and time dependent reduction in incorporation of 3H-labelled thymidine. The IC50 value increased with increase in incubation time and short term treatment had an inhibitory effect on the incorporation of thymidine. These effects are previously unreported for the used cell lines. It was observed for the first time that when in FCS containing solution, levels of resveratrol decreased. It was found that resveratrol induced a dose dependent accumulation in the S and G1 phases of the cell cycle in both cell lines. In addition, an enlargement of the HL-60 but not HepG2 nuclei was observed. The nuclear enlarging effect is previously unreported. Resveratrol was found to stimulate apoptosis in a dose dependent manner in HL-60 cells. Caspase-3 and Caspase-8 were furthermore found to be activated. Basal and TNF-a stimulated NF-kB activity was found to be inhibited by resveratrol in a dose dependent manner. Conclusion: Resveratrol modulates the cell cycle in a complex fashion. Apoptosis is stimulated in a dose dependent manner, with activation of the extrinsic and the intrinsic pathways. The involvement of NF-kB in the observed cellular effects remains unclear.