Dual regulatory effects of resveratrol on activation of NF-κB and cell proliferation in human embryonal kidney 293 cells

Resveratrol (3,4‘,5-trihydroxystilbene, Res), a naturally occurring polyphenol, exhibits antioxidant, antiinflammatory, potential chemopreventive and chemotherapeutic properties in preclinical studies. To further understand its potential clinical efficacy and safety, effect of Res at 10^-9-10^-4 mol/L on human embryonal kidney (HEK293) cell proliferation and its potential mechanism were investigated in present study. Cell viability was detected by using trypan blue dye exclusion method. Cell cycle and apoptosis were analyzed by flow cytometry with propidium iodide stain.Activation of nuclear factor-κB (NF-κB) was determined by luciferase reporter gene assay using stably transfected HEK293/κB-luc cells. Secretion of human interleukin-8(hlL-8) was measured by ELISA. Our results show that HEK293 cell proliferation was significantly stimulated by 10^-7 mol/L Res after treatment for 48 hours, or by 10^-8-10^-7mol/L Res combinated with 10 ng/mL TNFα for 24 h, but was suppressed by 10^-4 mol/L Res with or without TNFα. Both endogenous and TNFα-induced NF-κB activation were downregulated by Res at 10^-7 mol/L, but were upregulated at 10^-4 mol/L. With 10^-4 mol/L Res, the content of secreted IL-8 was increased, and apoptosis rate was increased from lessthan 5 % to 10%, together with significant cell-cycle arrest in S phase. TNFα has coordinative effects with Res on HEK293 cell apoptosis, cell-cycle arrest and IL-8 secretion. These results indicate that Res promotes cell proliferation at low concentration through down-regulation of NF-κB activation in HEK293, but suppresses its growth at high concentration through up-regulation of NF-κB activation, increasing IL-8 and cell-cycle arrest. As resveratrol has dual regulatory effect on cell proliferation in vitro, comprehensive evaluation of its potential clinical utility is needed.

Dual regulatory effects of resveratrol on activation of NF-κB and cell proliferation in human embryonal kidney 293 cells

Resveratrol (3,4′,5-trihydroxystilbene, Res), a naturally occurring polyphenol, exhibits antioxidant, anti-inflammatory, potential chemopreventive and chemotherapeutic properties in preclinical studies. To further understand its potential clinical efficacy and safety, effect of Res at 10⁻⁹–10⁻⁴ mol/L on human embryonal kidney (HEK293) cell proliferation and its potential mechanism were investigated in present study. Cell viability was detected by using trypan blue dye exclusion method. Cell cycle and apoptosis were analyzed by flow cytometry with propidium iodide stain. Activation of nuclear factor-kB (NF-kB) was determined by luciferase reporter gene assay using stably transfected HEK293/kB-1uc cells. Secretion of human interleukin-8 (hIL-8) was measured by ELISA. Our results show that HEK293 cell proliferation was significantly stimulated by 10⁻⁷ mol/L Res after treatment for 48 hours, or by 10⁻⁸-10⁻⁷ mol/L Res combinated with 10 ng/mL TNFα for 24 h, but was suppressed by 10⁻⁴ mol/L Res with or without TNFα. Both endogenous and TNFα-induced NF-kB activation were downregulated by Res at 10⁻⁷ mol/L, but were upregulated at 10⁻⁴ mol/L. With 10⁻⁴ mol/L Res, the content of secreted IL-8 was increased, and apoptosis rate was increased from less than 5% to 10%, together with significant cell-cycle arrest in S phase. TNFα has coordinative effects with Res on HEK293 cell apoptosis, cell-cycle arrest and IL-8 secretion. These results indicate that Res promotes cell proliferation at low concentration through down-regulation of NF-kB activation in HEK293, but suppresses its growth at high concentration through up-regulation of NF-kB activation, increasing IL-8 and cell-cycle arrest. As resveratrol has dual regulatory effect on cell proliferationin vitro, comprehensive evaluation of its potential clinical utility is needed.