Gallic Acid: Chemical Properties and Cellular Responses

Abstract

Gallic acid (3,4,5-trihydroxybenzoic acid), a polyphenol common in many plants has pharmaceutical properties with potential health benefits. As with most polyphenols, gallic acid exhibits both antioxidant and prooxidant properties. The connection between gallic acid acting both as a prooxidant and as an apoptosis-inducing agent is ill-defined. The research herein clearly demonstrates a cause-and-effect relationship between gallic acid’s production of hydrogen peroxide (H2O2) and its subsequent induction of apoptosis to human oral carcinoma HSC-2 cells. Using the FOX assay in a cell-free system, it was shown that gallic acid is a strong generator of H2O2. Reduced glutathione (GSH), a thiol-containing a tripeptide, is the main intracellular antioxidant in a cell’s repertoire of defenses against oxidative stress. Using the Intracellular Glutathione Assay, depletion of intracellular GSH, a sign of impending oxidative stress, was observed in HSC-2 cells. The potency of gallic acid to HSC-2 cells was lessened in the presence of scavengers of hydrogen peroxide, such as divalent cobalt. Flow cytometric analyses of HSC-2 cells treated with gallic acid indicated a concentration-dependent response for the induction of apoptosis, which was reversed in the presence of divalent cobalt. These studies showed that the proapoptotic activities of gallic acid to HSC-2 cancer cells were mediated through autooxidation of gallic acid leading to the induction of oxidative stress.