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

Escin, a Pentacyclic Triterpene, Chemosensitizes Human Tumor Cells through Inhibition of Nuclear Factor-κB Signaling Pathway

Kuzhuvelil B. Harikumar, Bokyung Sung, Manoj K. Pandey, Sushovan Guha, Sunil Krishnan and Bharat B. Aggarwal
Molecular Pharmacology May 2010, 77 (5) 818-827; DOI: https://doi.org/10.1124/mol.109.062760
Kuzhuvelil B. Harikumar
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bokyung Sung
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Manoj K. Pandey
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sushovan Guha
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sunil Krishnan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bharat B. Aggarwal
  • 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
Loading

Abstract

Agents that can enhance tumor cell apoptosis and inhibit invasion have potential for the treatment of cancer. Here, we report the identification of escin, a pentacyclic triterpenoid from horse chestnut that exhibits antitumor potential against leukemia and multiple myeloma. Whether examined by esterase staining, phosphatidyl-serine staining, DNA breakage, or caspase-mediated poly(ADP-ribose) polymerase cleavage, escin potentiated tumor necrosis factor (TNF)-induced apoptosis but inhibited tumor cell invasion. This correlated with the down-regulation of bcl-2, cellular inhibitor of apoptosis protein-2, cyclin D1, cyclooxygenase-2, intercellular adhesion molecule-1, matrix metalloproteinase-9, and vascular endothelial growth factor, which are all regulated by the activation of the transcription factor NF-κB. When examined by electrophoretic mobility shift assay, the triterpenoid suppressed nuclear factor-κB (NF-κB) activation induced by TNF and other inflammatory agents, and this correlated with the inhibition of IκBα phosphorylation and degradation, inhibition of IκB kinase complex (IKK) activation, suppression of p65 phosphorylation and nuclear translocation, and abrogation of NF-κB-dependent reporter activity. Overall, our results demonstrate that escin inhibits activation of NF-κB through inhibition of IKK, leading to down-regulation of NF-κB-regulated cell survival and metastatic gene products and thus resulting in sensitization of cells to cytokines and chemotherapeutic agents.

Footnotes

  • This work was supported by the National Institutes of Health National Cancer Institute [Grant CA124787-01A2]; the Clayton Foundation for Research; and the Center for Targeted Therapy of the M. D. Anderson Cancer Center.

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

    doi:10.1124/mol.109.062760.

  • ABBREVIATIONS:

    NF-κB
    nuclear factor-κB
    COX-2
    cyclooxygenase-2
    EMSA
    electrophoretic mobility-shift assay
    HIV-1
    human immunodeficiency virus-1
    IAP
    inhibitor of apoptosis protein
    ICAM-1
    intercellular adhesion molecule 1
    IKK
    IκB kinase complex
    MMP-9
    matrix metalloproteinase-9
    NIK
    nuclear factor-κB-inducing kinase
    PARP
    poly(ADP-ribose) polymerase
    ROS
    reactive oxygen species
    SEAP
    secretory alkaline phosphatase
    TNF
    tumor necrosis factor
    TNFR1
    tumor necrosis factor receptor 1
    TRADD
    tumor necrosis factor receptor 1-associated death domain
    TRAF2
    tumor necrosis factor receptor-associated factor-2
    VEGF
    vascular endothelial growth factor
    FBS
    fetal bovine serum
    JNK
    c-Jun NH2-terminal kinase
    MAPK
    mitogen-activated protein kinase
    PAGE
    polyacrylamide gel electrophoresis
    PBS
    phosphate-buffered saline
    FITC
    fluorescein isothiocyanate
    TUNEL
    terminal deoxynucleotidyl transferase dUTP nick-end labeling
    CSC
    cigarette smoke condensate
    PMA
    phorbol myristate acetate
    LPS
    lipopolysaccharide
    ALLN
    N-acetyl-leucyl-leucyl-norleucinal
    NAC
    N-acetyl cysteine
    OA
    okadaic acid
    IB
    immunoblotting
    IP
    immunoprecipitation.

    • Received November 24, 2009.
    • Accepted January 26, 2010.
  • Copyright © 2010 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: 77 (5)
Molecular Pharmacology
Vol. 77, Issue 5
1 May 2010
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • 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.
Escin, a Pentacyclic Triterpene, Chemosensitizes Human Tumor Cells through Inhibition of Nuclear Factor-κB Signaling Pathway
(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

Escin, a Pentacyclic Triterpene, Chemosensitizes Human Tumor Cells through Inhibition of Nuclear Factor-κB Signaling Pathway

Kuzhuvelil B. Harikumar, Bokyung Sung, Manoj K. Pandey, Sushovan Guha, Sunil Krishnan and Bharat B. Aggarwal
Molecular Pharmacology May 1, 2010, 77 (5) 818-827; DOI: https://doi.org/10.1124/mol.109.062760

Citation Manager Formats

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

Share
Research ArticleArticle

Escin, a Pentacyclic Triterpene, Chemosensitizes Human Tumor Cells through Inhibition of Nuclear Factor-κB Signaling Pathway

Kuzhuvelil B. Harikumar, Bokyung Sung, Manoj K. Pandey, Sushovan Guha, Sunil Krishnan and Bharat B. Aggarwal
Molecular Pharmacology May 1, 2010, 77 (5) 818-827; DOI: https://doi.org/10.1124/mol.109.062760
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Anti-aromatase activity of exemestane phase II metabolites
  • α-Conotoxin Binding Site on the GABAB Receptor
  • Upacicalcet binds to the amino acid binding site of CaSR
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 © 2022 by the American Society for Pharmacology and Experimental Therapeutics