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.
References (47)
- 1 On the Origin of Cancer Cells [DOI]
- 2 Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression [DOI]
- 3 Acidity Generated by the Tumor Microenvironment Drives Local Invasion [DOI]
- 4 Small Molecules Blocking the Entry of Severe Acute Respiratory Syndrome Coronavirus into Host Cells [DOI]
- 5 LACTIC DEHYDROGENASE IN HUMAN NEOPLASTIC TISSUES.
- 6 Tumor Cell Metabolism Imaging [DOI]
- 7 Anti-Cancer, Anti-Diabetic and Other Pharmacologic and Biological Activities of Penta-Galloyl-Glucose [DOI]
- 8 Inhibitory effect of methyl gallate and gallic acid on oral bacteria [DOI]
- 9 Knockdown of lactate dehydrogenase A suppresses tumor growth and metastasis of human hepatocellular carcinoma [DOI]
- 10 Free radical scavenging and antioxidant effects of lactate ion: an in vitro study [DOI]
- 11 Glycolytic metabolism and tumour response to fractionated irradiation [DOI]
- 12 Fucoidan from Seaweed Fucus vesiculosus Inhibits Migration and Invasion of Human Lung Cancer Cell via PI3K-Akt-mTOR Pathways [DOI]
- 13 On the Origin of Cancer [DOI]
- 14 Mitochondrial and plasma membrane lactate transporter and lactate dehydrogenase isoform expression in breast cancer cell lines [DOI]
- 15 UOK 262 cell line, fumarate hydratase deficient (FH−/FH−) hereditary leiomyomatosis renal cell carcinoma: in vitro and in vivo model of an aberrant energy metabolic pathway in human cancer [DOI]
- 16 PDK1 inhibition is a novel therapeutic target in multiple myeloma [DOI]
- 17 Prognostic and Predictive Role of Lactate Dehydrogenase 5 Expression in Colorectal Cancer Patients Treated with PTK787/ZK 222584 (Vatalanib) Antiangiogenic Therapy [DOI]
- 18 LDHA is necessary for the tumorigenicity of esophageal squamous cell carcinoma [DOI]
- 19 Expression Profiling in Progressive Stages of Fumarate-Hydratase Deficiency: The Contribution of Metabolic Changes to Tumorigenesis [DOI]
- 20 Anti-Helicobacter pylori Activity of Herbal Medicines. [DOI]
- 21 Gallotannins Inhibit Growth, Water-insoluble Glucan Synthesis, and Aggregation of Mutans Streptococci [DOI]
- 22 Penta- O -galloyl-beta- d -glucose suppresses tumor growth via inhibition of angiogenesis and stimulation of apoptosis: roles of cyclooxygenase-2 and mitogen-activated protein kinase pathways [DOI]
- 23 Phylogenetic and biogeographic diversification of Rhus (Anacardiaceae) in the Northern Hemisphere [DOI]
- 24 The Emerging “Hallmarks” of Metabolic Reprogramming and Immune Evasion: Distinct or Linked? [DOI]
- 25 Antibacterial Activity of Methyl Gallate Isolated from Galla Rhois or Carvacrol Combined with Nalidixic Acid Against Nalidixic Acid Resistant Bacteria [DOI]
- 26 Serum and Tissue LDH Levels in Patients with Breast/Gynaecological Cancer and Benign Diseases [DOI]
- 27 Growth-inhibitory effects of Galla Rhois-derived tannins on intestinal bacteria [DOI]
- 28 The anti-oxidant capacity of tumour glycolysis [DOI]
- 29 Mouse Genetics Suggests Cell-Context Dependency for Myc-Regulated Metabolic Enzymes during Tumorigenesis [DOI]
- 30 Antiviral compounds from traditional Chinese medicines Galla Chinese as inhibitors of HCV NS3 protease [DOI]
- 31 A glycoprotein from Laminaria japonica induces apoptosis in HT-29 colon cancer cells [DOI]
- 32 Autoxidation of gallic acid induces ROS-dependent death in human prostate cancer LNCaP cells.
- 33 Identification of a gene‐expression signature for predicting lymph node metastasis in patients with early stage cervical carcinoma [DOI]
- 34 Penta-O-galloyl-β- d -glucose Suppresses Prostate Cancer Bone Metastasis by Transcriptionally Repressing EGF-Induced MMP-9 Expression [DOI]
- 35 High throughput Screening to Identify Natural Human Monoamine Oxidase B Inhibitors [DOI]
- 36 Hamamelitannin from Witch Hazel (Hamamelis virginiana) Displays Specific Cytotoxic Activity against Colon Cancer Cells [DOI]
- 37 Cytotoxic Agents from Terminalia arjuna [DOI]
- 38 Efficacy of circulating plasma DNA as a diagnostic tool for advanced non-small cell lung cancer and its predictive utility for survival and response to chemotherapy [DOI]
- 39 Serum Lactate Dehydrogenase Levels and Glycolysis Significantly Correlate with Tumor VEGFA and VEGFR Expression in Metastatic Crc Patients [DOI]
- 40 Warburg Effect’s Manifestation in Aggressive Pheochromocytomas and Paragangliomas: Insights from a Mouse Cell Model Applied to Human Tumor Tissue [DOI]
- 41 Antiproliferative activity of various Uncaria tomentosa preparations on HL-60 promyelocytic leukemia cells.
- 42 Anti-proliferative effect of an extract of the root of Polygonum multiflorum Thunb. on MCF-7 human breast cancer cells and the possible mechanisms [DOI]
- 43 Oenothera paradoxa defatted seeds extract containing pentagalloylglucose and procyanidins potentiates the cytotoxicity of vincristine.
- 44 Phenolic Constituents of Galla Rhois with Hepatoprotective Effects on Tacrine- and Nitrofurantoin-Induced Cytotoxicity in Hep G2 Cells [DOI]
- 45 Screening the active constituents of Chinese medicinal herbs as potent inhibitors of Cdc25 tyrosine phosphatase, an activator of the mitosis-inducing p34cdc2kinase [DOI]
- 46 Phosphorylated pVEGFR2/KDR receptor expression in uveal melanomas: relation with HIF2α and survival [DOI]
- 47 Review of complementary and alternative medicine and selected nutraceuticals: background for a pilot study on nutrigenomic intervention in patients with advanced cancer.
Cited by 46
Tian T, Dai H, Zhang M · Acad Radiol · 2024
Sharma D, Singh M, Rani R. · Semin Cancer Biol · 2022
Sevastre AS, Manea EV, Popescu OS · Int J Mol Sci · 2022
Gupta GS. · Inflammation · 2022
Tan H, Wang H, Ma J · Acta Pharm Sin B · 2022
Mazzio E, Mack N, Badisa RB · Biomolecules · 2021
Mack N, Mazzio E, Badisa R · Cancer Genomics Proteomics · 2021
Mazzio E, Badisa R, Mack N · Cancer Genomics Proteomics · 2020
Maggini V, De Leo M, Granchi C · Sci Rep · 2019
Feng Y, Xiong Y, Qiao T · Cancer Med · 2018
Showing 42 of 46 known citations — external sources report more than can currently be individually listed.
Related research
- Herbal Approach towards the Cure of Diabetes Mellitus— A Review — shares topic coverage
- Phytotherapeutic Molecules & Antioxidants: A Novel & Secure Approach of Cancer Prevention — shares topic coverage
- Herbal Medicines Used by Tuberculosis Patients in Myanmar — shares topic coverage
- Natural Medicines Enhancing Neurite Growth in Central Nervous System Disorders: A Review — shares topic coverage
- Camel Feed Characterization of Ethiopian Somali Region Rangelands through Traditional Knowledge — shares topic coverage
Article metrics
Real usage data collected on this platform.
92
Page views
0
PDF downloads
4
Outbound clicks
46
Citations
Views over time
Views by country
Approximate, from request IP at view time — not citizenship or institution. Countries with fewer than 5 views are grouped as "Other".
Traffic sources
Referring site, by host.
Views and downloads exclude known bots/crawlers. Citations combines this platform's own DOI-resolved index with each external source's own reported total — see Cited by above for individually listed citing works. Last refreshed 0 seconds ago.