Suppression of TNF- induced NFB activity by gallic acid and its semi-synthetic esters: possible role in cancer chemoprevention
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Gallic acid (3,4,5-trihydroxybenzoic acid), found in many plants either in free-form or part of tannins, is known to possess anti-microbial, antioxidant and cytotoxic properties. NFB regulates the expression of several genes involved in carcinogenesis. These include anti-apoptotic, cytokines and cell cycle-regulatory genes. It is well established that the transcriptional factor NFB is deregulated in many forms of cancer. Thus, agents that can suppress NFB activation have the potential of suppressing carcinogenesis. In the present investigation, gallic acid was isolated from Alchornea glandulosa (Euphorbiaceae) and eight esters were synthesised. These compounds were evaluated against TNF--induced NFB activation with stably transfected 293/NFB-Luc human embryonic kidney cells. Gallates with IC50 values in a range of 10-56 mu M mediated inhibitory activity higher than gallic acid (IC50 76.0 +/- 4.9 mu M). In addition to inhibiting NFB activation, gallic acid mediated a modest cytotoxic effect, and some of the gallates affected cell viability at the tested concentrations. Based on these results, suppression of NFB activation by gallate esters could play a chemopreventive role in carcinogenesis.
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