Nuclear factor-kappaB as a switch in regulation of resveratrol-mediated apoptosis and erythrocytic differentiation in human leukaemia cells

Resveratrol exerts functions relating apoptosis and differentiation; nonetheless, the mechanisms remain unclear. We examined the regulation of resveratrol on apoptosis and erythrocytic (E)-differentiation in leukaemia cells. The results showed that resveratrol treatment for 24 h induced apoptosis in human leukaemia NB4, HL-60, and U937 cells. Resveratrol-treated K562 cells underwent erythrocyte (E)-differentiation and cell cycle arrest in S-phase, without apoptotic induction in the early stage, but with marked apoptosis in the later stages. Resveratrol-induced apoptosis could be accompanied by P38 downregulation, and E-differentiation could occur with PI3K/Akt upregulation. Downstream NF-κB was increased by resveratrol treatment for 24 h, while luciferase activity was decreased by resveratrol treatment for 72 h. Similar changes were discovered for nuclear levels and NF-κB-DNA binding activity. In conclusion, resveratrol induced differential responses through different signalling pathways, including PI3K/Akt and P38/MAPK, leading to opposing expressions of NF-κB. NF-κB could be a switch for regulating E-differentiation and apoptosis in resveratrol-stimulated K562 cells.