Inactivation of Nuclear Factor-κB by citrus flavanone hesperidin contributes to apoptosis and chemo-sensitizing effect in Ramos cells

Hesperidin, a flavonoid present in fruits and vegetables, possesses anti-inflammatory and chemopreventive effects. Some evidence implies that hesperidin may recruit Peroxisome Proliferator-Activated Receptor-gamma (PPARγ) to exert biological action. It has been shown also that inactivation of Nuclear Factor-kappaB is another mechanism of flavonoids' action. Therefore, we wished to investigate the role of these transcription factors in apoptosis induced by hesperidin in Ramos Burkitt's lymphoma cells. We found that incubation of Ramos cells with hesperidin abrogates constitutive and doxorubicin-induced NF-κB activation through inhibition of phosphorylation of its inhibitory subunits (IκB). Moreover, our results showed that incubation of Ramos cells with hesperidin resulted in inhibition of proliferation and apoptosis in a PPARγ-independent way. Our results demonstrated that hesperidin inhibits proliferation of Ramos cells and sensitizes them to doxorubicin-induced apoptosis through inhibition of both constitutive and doxorubicin-mediated NF-κB activation in a PPARγ-independent manner.