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 (IC 50 < 1 µ g/mL) inhibitor of human LDH-A ( h LDH-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 h LDH-A inhibition, present at ~9.95 ± 0.34% dry weight. Theoretical molecular docking studies of h LDH-A indicate that PGG acts through competitive binding at the NADH cofactor site, effects confirmed by functional enzyme studies where the IC 50 = 27.32 nM was reversed with increasing concentration of NADH. Moreover, we confirm protein expression of h LDH-A in MDA-231 human breast carcinoma cells and show that PGG was toxic (LC 50 = 94.18 µ M), parallel to attenuated lactic acid production (IC 50 = 97.81 µ M). In a 72-hour cell proliferation assay, PGG was found to be a potent cytostatic agent with ability to halt cell division (IC 50 = 1.2 µ M) relative to paclitaxel (IC 50 < 100 nM). In summary, these findings demonstrate that PGG is a potent h LDH-A inhibitor with significant capacity to halt proliferation of human breast cancer cells.
Deiab, S., Mazzio, E., Eyunni, S., McTier, O., Mateeva, N., Elshami, F., & Soliman, K. F. A. (2015). 1,2,3,4,6-Penta-O-galloylglucose within Galla Chinensis inhibits human LDH-A and attenuates cell proliferation in MDA-MB-231 breast cancer cells. Evidence-Based Complementary and Alternative Medicine, 2015. https://doi.org/10.1155/2015/276946