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

16Citations
Citations of this article
12Readers
Mendeley users who have this article in their library.

Abstract

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.

Cite

CITATION STYLE

APA

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

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free