High-Throughput Screening to Identify Plant Derived Human LDH-A Inhibitors
Identifieur interne : 001240 ( Main/Exploration ); précédent : 001239; suivant : 001241High-Throughput Screening to Identify Plant Derived Human LDH-A Inhibitors
Auteurs : S. Deiab [États-Unis] ; E. Mazzio [États-Unis] ; S. Messeha [États-Unis] ; N. Mack [États-Unis] ; K. F. A. Soliman [États-Unis]Source :
- European journal of medicinal plants [ 2231-0894 ] ; 2013.
Abstract
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.
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
The protein sequence of purified enzyme was confirmed using 1D gel electrophoresis- MALDI
Of the natural extracts tested, the lowest IC50s [<0.001 mg/ml] were obtained by: Chinese Gallnut (
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.
Url:
PubMed: 24478981
PubMed Central: 3903096
Affiliations:
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Mazzio</name><affiliation wicri:level="1"><nlm:aff id="A1">College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee, Florida 32307, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee, Florida 32307</wicri:regionArea><wicri:noRegion>Florida 32307</wicri:noRegion></affiliation></author><author><name sortKey="Messeha, S" sort="Messeha, S" uniqKey="Messeha S" first="S." last="Messeha">S. Messeha</name><affiliation wicri:level="1"><nlm:aff id="A1">College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee, Florida 32307, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee, Florida 32307</wicri:regionArea><wicri:noRegion>Florida 32307</wicri:noRegion></affiliation></author><author><name sortKey="Mack, N" sort="Mack, N" uniqKey="Mack N" first="N." last="Mack">N. Mack</name><affiliation wicri:level="1"><nlm:aff id="A1">College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee, Florida 32307, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee, Florida 32307</wicri:regionArea><wicri:noRegion>Florida 32307</wicri:noRegion></affiliation></author><author><name sortKey="Soliman, K F A" sort="Soliman, K F A" uniqKey="Soliman K" first="K. F. A." last="Soliman">K. F. A. Soliman</name><affiliation wicri:level="1"><nlm:aff id="A1">College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee, Florida 32307, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee, Florida 32307</wicri:regionArea><wicri:noRegion>Florida 32307</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24478981</idno><idno type="pmc">3903096</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3903096</idno><idno type="RBID">PMC:3903096</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">000A56</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000A56</idno><idno type="wicri:Area/Pmc/Curation">000A56</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000A56</idno><idno type="wicri:Area/Pmc/Checkpoint">000694</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000694</idno><idno type="wicri:Area/Ncbi/Merge">000423</idno><idno type="wicri:Area/Ncbi/Curation">000423</idno><idno type="wicri:Area/Ncbi/Checkpoint">000423</idno><idno type="wicri:Area/Main/Merge">001242</idno><idno type="wicri:Area/Main/Curation">001240</idno><idno type="wicri:Area/Main/Exploration">001240</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">High-Throughput Screening to Identify Plant Derived Human LDH-A Inhibitors</title><author><name sortKey="Deiab, S" sort="Deiab, S" uniqKey="Deiab S" first="S." last="Deiab">S. Deiab</name><affiliation wicri:level="1"><nlm:aff id="A1">College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee, Florida 32307, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee, Florida 32307</wicri:regionArea><wicri:noRegion>Florida 32307</wicri:noRegion></affiliation></author><author><name sortKey="Mazzio, E" sort="Mazzio, E" uniqKey="Mazzio E" first="E." last="Mazzio">E. Mazzio</name><affiliation wicri:level="1"><nlm:aff id="A1">College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee, Florida 32307, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee, Florida 32307</wicri:regionArea><wicri:noRegion>Florida 32307</wicri:noRegion></affiliation></author><author><name sortKey="Messeha, S" sort="Messeha, S" uniqKey="Messeha S" first="S." last="Messeha">S. Messeha</name><affiliation wicri:level="1"><nlm:aff id="A1">College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee, Florida 32307, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee, Florida 32307</wicri:regionArea><wicri:noRegion>Florida 32307</wicri:noRegion></affiliation></author><author><name sortKey="Mack, N" sort="Mack, N" uniqKey="Mack N" first="N." last="Mack">N. Mack</name><affiliation wicri:level="1"><nlm:aff id="A1">College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee, Florida 32307, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee, Florida 32307</wicri:regionArea><wicri:noRegion>Florida 32307</wicri:noRegion></affiliation></author><author><name sortKey="Soliman, K F A" sort="Soliman, K F A" uniqKey="Soliman K" first="K. F. A." last="Soliman">K. F. A. Soliman</name><affiliation wicri:level="1"><nlm:aff id="A1">College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee, Florida 32307, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee, Florida 32307</wicri:regionArea><wicri:noRegion>Florida 32307</wicri:noRegion></affiliation></author></analytic><series><title level="j">European journal of medicinal plants</title><idno type="eISSN">2231-0894</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S1"><title>Aims</title><p id="P1">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.</p></sec><sec id="S2"><title>Study Design</title><p id="P2">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 <italic>mg/ml</italic>) for capacity to inhibit activity of recombinant full length human LDHA; EC .<italic>1.1.1.27</italic>.</p></sec><sec id="S3"><title>Methodology</title><p id="P3">The protein sequence of purified enzyme was confirmed using 1D gel electrophoresis- MALDI<italic>-TOF-</italic>MS/MS, enzyme activity was validated by oxidation of NADH (500μM) and kinetic inhibition established in the presence of a known inhibitor (Oxalic Acid).</p></sec><sec id="S4"><title>Results</title><p id="P4">Of the natural extracts tested, the lowest IC<sub>50</sub>s [<0.001 mg/ml] were obtained by: Chinese Gallnut (<italic>Melaphis chinensis gallnut)</italic>, Bladderwrack (<italic>Fucus vesiculosus)</italic>, Kelp (<italic>Laminaria Japonica</italic>) and Babul (<italic>Acacia Arabica)</italic>. Forty-six additional herbs contained significant LDH-A inhibitory properties with IC<sub>50</sub>s [<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.</p></sec><sec id="S5"><title>Conclusion</title><p id="P5">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.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Le, A" uniqKey="Le A">A Le</name></author><author><name sortKey="Cooper, Cr" uniqKey="Cooper C">CR Cooper</name></author><author><name sortKey="Gouw, Am" uniqKey="Gouw A">AM Gouw</name></author><author><name sortKey="Dinavahi, R" uniqKey="Dinavahi R">R Dinavahi</name></author><author><name sortKey="Maitra, A" uniqKey="Maitra A">A Maitra</name></author><author><name sortKey="Deck, Lm" uniqKey="Deck L">LM Deck</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Goldman, Rd" uniqKey="Goldman R">RD Goldman</name></author><author><name sortKey="Kaplan, No" uniqKey="Kaplan N">NO Kaplan</name></author><author><name sortKey="Hall, Tc" uniqKey="Hall T">TC 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Moyer</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>États-Unis</li></country></list><tree><country name="États-Unis"><noRegion><name sortKey="Deiab, S" sort="Deiab, S" uniqKey="Deiab S" first="S." last="Deiab">S. Deiab</name></noRegion><name sortKey="Mack, N" sort="Mack, N" uniqKey="Mack N" first="N." last="Mack">N. Mack</name><name sortKey="Mazzio, E" sort="Mazzio, E" uniqKey="Mazzio E" first="E." last="Mazzio">E. Mazzio</name><name sortKey="Messeha, S" sort="Messeha, S" uniqKey="Messeha S" first="S." last="Messeha">S. Messeha</name><name sortKey="Soliman, K F A" sort="Soliman, K F A" uniqKey="Soliman K" first="K. F. A." last="Soliman">K. F. A. Soliman</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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