Suppression of TNF-α induced NFκB activity by gallic acid and its semi-synthetic esters: possible role in cancer chemoprevention.
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. NFκB 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 NFκB is deregulated in many forms of cancer. Thus, agents that can suppress NFκB 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-α-induced NFκB activation with stably transfected 293/NFκB-Luc human embryonic kidney cells. Gallates with IC(50) values in a range of 10-56 µM mediated inhibitory activity higher than gallic acid (IC(50) 76.0 ± 4.9 µM). In addition to inhibiting NFκB 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 NFκB activation by gallate esters could play a chemopreventive role in carcinogenesis.
Morais
Mauro C C
MC
College of Pharmacy, University of Hawaii, Hawaii, Hilo 96720, USA.
Luqman
Suaib
S
Kondratyuk
Tamara P
TP
Petronio
Maicon S
MS
Regasini
Luis O
LO
Silva
Dulce H S
DH
Bolzani
Vanderlan S
VS
Soares
Christiane P
CP
Pezzuto
John M
JM
D000704:Analysis of Variance; D002460:Cell Line; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D019665:Euphorbiaceae / Q000737:chemistry*; D005707:Gallic Acid / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D008156:Luciferases; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009369:Neoplasms / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D005707:Gallic Acid; D008156:Luciferases