Effect of the hesperetin and naringenin on pp60^v-src-induced NF-κB activation

The effects of hesperetin and naringenin on NF-κB activation were investigated in normal rat kidney cells transformed by temperature sensitive Rous Sarcoma Virus (tsNRK). The flavonoids, naringenin and hesperetin, significantly reduced v-Src-induced NF-κB activation as well as phosphorylation of Akt and GSK-3 in tsNRK cells, whereas these compounds did not effect on platelet-derived growth factor (PDGF)-induced NF-κB activation in NIH3T3γ1 cells. In addition, the DNA binding activity of SP-1 was also reduced but that of AP-1 was not affected by the compounds. Our study suggests that Src-induced NF-κB activation could occur via Akt-GSK-3 pathway without IκBα degradation and that naringenin and hesperetin could be used in the treatment of cancer through the inhibition of NF-κB activation.