Suppression of TNF-α induced NFκB activity by gallic acid and its semi-synthetic alkyl-gallates: Possible role in cancer chemoprevention

Abstract NFκB, a transcription factor, regulates the expression of a number of genes involved in carcinogenesis. Thus, agents that can suppress NFκB activation have the potential to suppress carcinogenesis. In the present investigation, gallic acid was isolated from Alchornea glandulosa (Euphorbiaceae) and eight semi-synthetic alkyl gallates were prepared from the reaction of the corresponding alcohols with gallic acid at 80oC for 48 h in good yields (70-97%). All the compounds were evaluated against TNF-α-induced NFκB activation with stable transfected 293/NFκB-Luc human embryonic kidney cells. Treatment of cells with gallic acid and the gallate esters (20 µg/ml) significantly reduced TNF-α induced NFκB activation. With IC50 values in a range of 10 to 50 µM, gallic acid esters mediated inhibitory activity greater than that of gallic acid (IC50 76 µM). In addition to the inhibition of NFκB activation, gallic acid mediated a modest cytotoxic effect, but none of the gallate esters affected cell viability at the tested concentrations. Based on these encouraging intracellular responses, we suggest suppression of NFκB activation by gallate esters could play a chemopreventive role in carcinogenesis, and further investigations are warranted.