High-Throughput Screening to Identify Plant Derived Human LDH-A Inhibitors.
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Date
2013-10
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Abstract
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.
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Keywords
Lactic acid, Warburg, LDH-A, inhibitor, herbs, medicinal plants
Citation
Deiab S, Mazzio E, Messeha S, Mack N, Soliman K F A. High-Throughput Screening to Identify Plant Derived Human LDH-A Inhibitors. European Journal of Medicinal Plants. 2013 Oct-Dec; 3(4): 603-615.