Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Molecular Pharmacology
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Molecular Pharmacology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Anacardic Acid Inhibits the Catalytic Activity of Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9

Athira Omanakuttan, Jyotsna Nambiar, Rodney M. Harris, Chinchu Bose, Nanjan Pandurangan, Rebu K. Varghese, Geetha B. Kumar, John A. Tainer, Asoke Banerji, J. Jefferson P. Perry and Bipin G. Nair
Molecular Pharmacology October 2012, 82 (4) 614-622; DOI: https://doi.org/10.1124/mol.112.079020
Athira Omanakuttan
Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Kollam, Kerala, India (A.O., J.N., C.B., N.P., R.K.V., G.B.K., A.B., J.J.P.P., B.G.N.); 1060 Discovery Engineering, San Diego, California (R.M.H.); Skaggs Institute for Chemical Biology and Department of Molecular Biology, the Scripps Research Institute, La Jolla, California (J.A.T., J.J.P.P.); and Lawrence Berkeley National Laboratory, Berkeley, California (J.A.T.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jyotsna Nambiar
Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Kollam, Kerala, India (A.O., J.N., C.B., N.P., R.K.V., G.B.K., A.B., J.J.P.P., B.G.N.); 1060 Discovery Engineering, San Diego, California (R.M.H.); Skaggs Institute for Chemical Biology and Department of Molecular Biology, the Scripps Research Institute, La Jolla, California (J.A.T., J.J.P.P.); and Lawrence Berkeley National Laboratory, Berkeley, California (J.A.T.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rodney M. Harris
Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Kollam, Kerala, India (A.O., J.N., C.B., N.P., R.K.V., G.B.K., A.B., J.J.P.P., B.G.N.); 1060 Discovery Engineering, San Diego, California (R.M.H.); Skaggs Institute for Chemical Biology and Department of Molecular Biology, the Scripps Research Institute, La Jolla, California (J.A.T., J.J.P.P.); and Lawrence Berkeley National Laboratory, Berkeley, California (J.A.T.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Chinchu Bose
Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Kollam, Kerala, India (A.O., J.N., C.B., N.P., R.K.V., G.B.K., A.B., J.J.P.P., B.G.N.); 1060 Discovery Engineering, San Diego, California (R.M.H.); Skaggs Institute for Chemical Biology and Department of Molecular Biology, the Scripps Research Institute, La Jolla, California (J.A.T., J.J.P.P.); and Lawrence Berkeley National Laboratory, Berkeley, California (J.A.T.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nanjan Pandurangan
Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Kollam, Kerala, India (A.O., J.N., C.B., N.P., R.K.V., G.B.K., A.B., J.J.P.P., B.G.N.); 1060 Discovery Engineering, San Diego, California (R.M.H.); Skaggs Institute for Chemical Biology and Department of Molecular Biology, the Scripps Research Institute, La Jolla, California (J.A.T., J.J.P.P.); and Lawrence Berkeley National Laboratory, Berkeley, California (J.A.T.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rebu K. Varghese
Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Kollam, Kerala, India (A.O., J.N., C.B., N.P., R.K.V., G.B.K., A.B., J.J.P.P., B.G.N.); 1060 Discovery Engineering, San Diego, California (R.M.H.); Skaggs Institute for Chemical Biology and Department of Molecular Biology, the Scripps Research Institute, La Jolla, California (J.A.T., J.J.P.P.); and Lawrence Berkeley National Laboratory, Berkeley, California (J.A.T.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Geetha B. Kumar
Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Kollam, Kerala, India (A.O., J.N., C.B., N.P., R.K.V., G.B.K., A.B., J.J.P.P., B.G.N.); 1060 Discovery Engineering, San Diego, California (R.M.H.); Skaggs Institute for Chemical Biology and Department of Molecular Biology, the Scripps Research Institute, La Jolla, California (J.A.T., J.J.P.P.); and Lawrence Berkeley National Laboratory, Berkeley, California (J.A.T.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
John A. Tainer
Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Kollam, Kerala, India (A.O., J.N., C.B., N.P., R.K.V., G.B.K., A.B., J.J.P.P., B.G.N.); 1060 Discovery Engineering, San Diego, California (R.M.H.); Skaggs Institute for Chemical Biology and Department of Molecular Biology, the Scripps Research Institute, La Jolla, California (J.A.T., J.J.P.P.); and Lawrence Berkeley National Laboratory, Berkeley, California (J.A.T.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Asoke Banerji
Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Kollam, Kerala, India (A.O., J.N., C.B., N.P., R.K.V., G.B.K., A.B., J.J.P.P., B.G.N.); 1060 Discovery Engineering, San Diego, California (R.M.H.); Skaggs Institute for Chemical Biology and Department of Molecular Biology, the Scripps Research Institute, La Jolla, California (J.A.T., J.J.P.P.); and Lawrence Berkeley National Laboratory, Berkeley, California (J.A.T.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
J. Jefferson P. Perry
Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Kollam, Kerala, India (A.O., J.N., C.B., N.P., R.K.V., G.B.K., A.B., J.J.P.P., B.G.N.); 1060 Discovery Engineering, San Diego, California (R.M.H.); Skaggs Institute for Chemical Biology and Department of Molecular Biology, the Scripps Research Institute, La Jolla, California (J.A.T., J.J.P.P.); and Lawrence Berkeley National Laboratory, Berkeley, California (J.A.T.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bipin G. Nair
Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Kollam, Kerala, India (A.O., J.N., C.B., N.P., R.K.V., G.B.K., A.B., J.J.P.P., B.G.N.); 1060 Discovery Engineering, San Diego, California (R.M.H.); Skaggs Institute for Chemical Biology and Department of Molecular Biology, the Scripps Research Institute, La Jolla, California (J.A.T., J.J.P.P.); and Lawrence Berkeley National Laboratory, Berkeley, California (J.A.T.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF
Loading

Abstract

Cashew nut shell liquid (CNSL) has been used in traditional medicine for the treatment of a wide variety of pathophysiological conditions. To further define the mechanism of CNSL action, we investigated the effect of cashew nut shell extract (CNSE) on two matrix metalloproteinases, MMP-2/gelatinase A and MMP-9/gelatinase B, which are known to have critical roles in several disease states. We observed that the major constituent of CNSE, anacardic acid, markedly inhibited the gelatinase activity of 3T3-L1 cells. Our gelatin zymography studies on these two secreted gelatinases, present in the conditioned media from 3T3-L1 cells, established that anacardic acid directly inhibited the catalytic activities of both MMP-2 and MMP-9. Our docking studies suggested that anacardic acid binds into the MMP-2/9 active site, with the carboxylate group of anacardic acid chelating the catalytic zinc ion and forming a hydrogen bond to a key catalytic glutamate side chain and the C15 aliphatic group being accommodated within the relatively large S1′ pocket of these gelatinases. In agreement with the docking results, our fluorescence-based studies on the recombinant MMP-2 catalytic core domain demonstrated that anacardic acid directly inhibits substrate peptide cleavage in a dose-dependent manner, with an IC50 of 11.11 μM. In addition, our gelatinase zymography and fluorescence data confirmed that the cardol-cardanol mixture, salicylic acid, and aspirin, all of which lack key functional groups present in anacardic acid, are much weaker MMP-2/MMP-9 inhibitors. Our results provide the first evidence for inhibition of gelatinase catalytic activity by anacardic acid, providing a novel template for drug discovery and a molecular mechanism potentially involved in CNSL therapeutic action.

Footnotes

  • ↵Embedded Image The online version of this article (available at http://molpharm.aspetjournals.org) contains supplemental material.

  • This work was supported in part by Amrita University Research, the National Institutes of Health National Cancer Institute [Grant CA92584]; the National Institutes of Heath National Institute of Arthritis and Musculoskeletal and Skin Diseases [Grant AR059968]; and the Council of Scientific and Industrial Research and University Grants Commission (junior research fellowships to A.O. and J.N., respectively).

  • Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.

    http://dx.doi.org/10.1124/mol.112.079020.

  • ABBREVIATIONS:

    CNSL
    cashew nut shell liquid
    HAT
    histone acetyltransferase
    MMP
    matrix metalloproteinase
    PE
    petroleum ether
    CNSE
    cashew nut shell extract
    HPLC
    high-performance liquid chromatography
    DMSO
    dimethyl sulfoxide
    DMEM
    Dulbecco's modified Eagle's medium
    MTT
    3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide
    SA
    salicylic acid
    PDB
    Protein Data Bank
    Mca
    (7-methoxycoumarinyl) a cetyl
    Dap
    [3(2-dinitrophenyl 2,3-diaminopropionyl].

  • Received March 29, 2012.
  • Accepted June 28, 2012.
  • Copyright © 2012 The American Society for Pharmacology and Experimental Therapeutics
View Full Text

MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Molecular Pharmacology: 82 (4)
Molecular Pharmacology
Vol. 82, Issue 4
1 Oct 2012
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Pharmacology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Anacardic Acid Inhibits the Catalytic Activity of Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Inhibition of Gelatinases by Anacardic Acid

Athira Omanakuttan, Jyotsna Nambiar, Rodney M. Harris, Chinchu Bose, Nanjan Pandurangan, Rebu K. Varghese, Geetha B. Kumar, John A. Tainer, Asoke Banerji, J. Jefferson P. Perry and Bipin G. Nair
Molecular Pharmacology October 1, 2012, 82 (4) 614-622; DOI: https://doi.org/10.1124/mol.112.079020

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleArticle

Inhibition of Gelatinases by Anacardic Acid

Athira Omanakuttan, Jyotsna Nambiar, Rodney M. Harris, Chinchu Bose, Nanjan Pandurangan, Rebu K. Varghese, Geetha B. Kumar, John A. Tainer, Asoke Banerji, J. Jefferson P. Perry and Bipin G. Nair
Molecular Pharmacology October 1, 2012, 82 (4) 614-622; DOI: https://doi.org/10.1124/mol.112.079020
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Authorship Contributions
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Mechanism of the selective action of paraherquamide A
  • Relapsed-Leukemia Model with NT5C2/PRPS1 Hotspot Mutations
  • The Binding Site for KCI807 in the Androgen Receptor
Show more Articles

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About Molecular Pharmacology
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics