Selective Induction of Cell Death in Cancer Cells by Gallic Acid.

Abstract

Gallic acid (3,4,5-trihydroxybenzoic acid) is a naturally occurring plant phenol obtained by the hydrolysis of tannins and is know to show some pharmacological activities. In screening anti-cancer agents in traditional Chinese medicines, gallic acid was found to show cytotoxicity against all cancer cells that we examined in this study (IC50s: 4.8-13.2 micrograms/ml). Gallic acid was found to show cytotoxicity against primary cultured rat hepatocytes and macrophages, and lesser cytotoxicity against fibroblasts and endothelial cells. Cell death in dRLh-84 cells occurred within 6h after gallic acid treatment at a concentration of more than 20 micrograms/ml. A study of structurally related compounds suggested that the cytotoxicity shown by gallic acid was not a common feature in phenolic compounds, but was a fairly specific characteristic of gallic acid. That is, three adjacent phenolic hydroxyl groups of gallic acid were responsible for the cytotoxicity, and the carboxyl group was not responsible, but seemed to be implicated in distinguishing between normal cells and cancer cells.

Antiproliferative Constituents in the Plant 8. Seeds of Rhynchosia volubilis.

“…A similar result has already been reported against rat hepatoma (dRLh-84) cells by Inoue et al 12) We have also observed the phenomenon that the antiproliferative activity of caffeic acid is lowered by esterification. 1) In spite of structural differences, 5 and 3 showed similar activity.…”

“…And a carboxyl group is likely to be necessary in order for gallic acid to show selectivity to cancer cells, since pyrogallol killed not only dRLh-84 cells, but also primary cultured rat hepatocytes. 12) Furthermore, they also disclosed that the cell death induced by gallic acid was accompanied by internucleosomal DNA fragmentation characteristic of apoptosis. 13) In order to clarify in more detail the structure-antiproliferative activity relationship of gallic acid derivatives, we tested for the antiproliferative activity of ellagic acid and three related phenol carboxylic acids (Fig.…”

Ca2+-Dependent Caspase Activation by Gallic Acid Derivatives.

“…5) In addition, the study of the signaling pathway indicated that intracellular Ca 2ϩ may play an important role in GD-1 and GD-3-induced apoptosis as well as GA-induced apoptosis, but ROS was involved only in GA-induced apoptosis. 5) To clarify the mechanism by which GDs induce apoptosis and the difference in the signaling pathway elicited by GDs or GA, we asked in the present study whether GDs activate caspase-3, a downstream caspase in the signaling pathway leading to apoptosis.…”

Gallic Acid Suppresses Lipopolysaccharide-Induced Nuclear Factor-κB Signaling by Preventing RelA Acetylation in A549 Lung Cancer Cells

“…Gallic acid is cytotoxic to cancer cells and has anti-inflammatory and antimutagenic properties (2,3). Gallic acid has been described as an excellent free radical scavenger and as an inducer of differentiation and programmed cell death in a number of tumor cell lines (4,5). Recently, it was revealed that gallic acid from rose flowers exhibits antioxidative effects even in senescence-accelerated mice and can restore the activities of catalase and gluthatione peroxidase (6).…”