The Effect Of Baicalein On NF-κB And NF-κB-regulated Target Genes In Hela Cells

The transcription factor NF-κB is the most common and abundant of all transcription factors.Regulated by diverse stimuli including genotoxic,inflammatory,and oxidative stresses.Activation of NF-κB has been linked to various cellular processes in cancer,including inflammation,transformation,proliferation,angiogenesis,invasion,metastasis,chemoresistance,and radioresistance.Although acute inflammation mediates innate and humoral immunity,chronic inflammation has been linked to tumorigenesis.Thus,inhibition of NF-κB has therapeutic potential in sensitization of tumors to chemotherapeutic agents.We identifid baicalein from Scutellaria baicalensis as an inhibitor of NF-κB activation.We found that baicalein suppressed TNF-α-induced NF-κB activation in a dose-dependent manner by the NF-κB luciferase reporter assay,.It also inhibited TNF-α-induced nuclear translocation of p65 through inhibition of phosphorylation and degradation of IκBα.Furthermore,baicalein blocked the TNF-α-induced expression of NF-κB target genes involved in anti-apoptosis(cIAP-1,cIAP-2,FLIP and BCL-2),proliferation(COX-2,cyclin D1 and c-Myc),invasion(MMP-9),angiogenesis(VEGF)and major inflammatory cytokines(IL-8 and MCP1).The flw cytometric analysis indicated that baicalein potentiated TNF-α-induced apoptosis and induced G1 phase arrest in HeLa cells.Moreover,baicalein signifi cantly blocked activation of p38,extracellular signal-regulated kinase 1/2(ERK1/2).Our results imply that baicalein could be a lead compound for the modulation of inflmmatory diseases as well as certain cancers in which inhibition of NF-κB activity may be desirable.