High-Throughput Screening to Identify Plant Derived Human LDH-A Inhibitors
S. Deiab, E. Mazzio, S. Messeha, N. Mack, K. F. A. Soliman
European Journal of Medicinal Plants · pp. 603–615 · Published 6 Sep 2013
10.9734/EJMP/2013/5995Abstract
Aims: Lactate dehydrogenase (LDH)-A is highly expressed in diverse human malignant tumors, parallel to aggressive metastatic disease, resistance to radiation /chemotherapy and clinically poor outcome. Although this enzyme constitutes a plausible target in treatment of advanced cancer, there are few known LDH-A inhibitors. Study Design: In this work, we utilized a high-throughput enzyme micro-array format to screen and evaluate > 900 commonly used medicinal plant extracts (0.00001-.5 mg/ml) for capacity to inhibit activity of recombinant full length human LDHA; EC .1.1.1.27. Methodology: The protein sequence of purified enzyme was confirmed using 1D gel electrophoresis- MALDI-TOF-MS/MS, enzyme activity was validated by oxidation of NADH (500µM) and kinetic inhibition established in the presence of a known inhibitor (Oxalic Acid). Results: Of the natural extracts tested, the lowest IC50s [<0.001 mg/ml] were obtained by: Chinese Gallnut (Melaphis chinensis gallnut), Bladderwrack (Fucus vesiculosus), Kelp (Laminaria Japonica) and Babul (Acacia Arabica). Forty-six additional herbs contained significant LDH-A inhibitory properties with IC50s [<0.07 mg/ml], some of which have common names of Arjun, Pipsissewa, Cinnamon, Pink Rose Buds/ Petals, Wintergreen, Cat’s Claw, Witch Hazel Root and Rhodiola Root. Conclusion: These findings reflect relative potency by rank of commonly used herbs and plants that contain human LDH-A inhibitory properties. Future research will be required to isolate chemical constituents within these plants responsible for LDH-A inhibition and investigate potential therapeutic application.
Cited by 42
Singh AK, Sharma N, Ghosh M · Crit Rev Food Sci Nutr · 2017
De Leo M, Peruzzi L, Granchi C · J Nat Prod · 2017
Granchi C, Fortunato S, Meini S · J Agric Food Chem · 2017
Mack N, Mazzio EA, Bauer D · Anticancer Res · 2017
Colantonio S, Rivers JK. · J Cutan Med Surg · 2017
Kim EY, Choi HJ, Park MJ · Am J Chin Med · 2016
Stine ZE, Walton ZE, Altman BJ · Cancer Discov · 2015
Valvona CJ, Fillmore HL, Nunn PB · Brain Pathol · 2016
Deiab S, Mazzio E, Eyunni S · Evid Based Complement Alternat Med · 2015
Augoff K, Hryniewicz-Jankowska A, Tabola R. · Cancer Lett · 2015
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