A characteristic feature of aggressive
malignancy is the overexpression of
lactic acid dehydrogenase- (
LDH-) A, concomitant to pericellular accumulation of
lactate. In a recent high-throughput screening, we identified Rhus chinensis (Mill.) gallnut (RCG) (also known as
Galla Chinensis) extract as a potent (IC50 < 1 µg/mL) inhibitor of human
LDH-A (hLDH-A). In this study, through bioactivity guided fractionation of the
crude extract, the data demonstrate that penta-1,2,3,4,6-O-galloyl-β-D-glucose (
PGG) was a primary constituent responsible for hLDH-A inhibition, present at ~9.95 ± 0.34% dry weight. Theoretical molecular docking studies of hLDH-A indicate that
PGG acts through competitive binding at the
NADH cofactor site, effects confirmed by functional
enzyme studies where the IC50 = 27.32 nM was reversed with increasing concentration of
NADH. Moreover, we confirm
protein expression of hLDH-A in MDA-231 human
breast carcinoma cells and show that
PGG was toxic (LC50 = 94.18 µM), parallel to attenuated
lactic acid production (IC50 = 97.81 µM). In a 72-hour cell proliferation assay,
PGG was found to be a potent
cytostatic agent with ability to halt cell division (IC50 = 1.2 µM) relative to
paclitaxel (IC50 < 100 nM). In summary, these findings demonstrate that
PGG is a potent hLDH-A inhibitor with significant capacity to halt proliferation of human
breast cancer cells.