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
Journal of Pharmacology and Experimental Therapeutics
  • 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
Journal of Pharmacology and Experimental Therapeutics

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 jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleInflammation, Immunopharmacology, and Asthma

Positional Isomers of Aspirin Are Equally Potent in Inhibiting Colon Cancer Cell Growth: Differences in Mode of Cyclooxygenase Inhibition

Ravinder Kodela, Mitali Chattopadhyay, Satindra Goswami, Zong Yuan Gan, Praveen P. N. Rao, Kamran V. Nia, Carlos A. Velázquez-Martínez and Khosrow Kashfi
Journal of Pharmacology and Experimental Therapeutics April 2013, 345 (1) 85-94; DOI: https://doi.org/10.1124/jpet.112.201970
Ravinder Kodela
Department of Physiology, Pharmacology, and Neuroscience, Sophie Davis School of Biomedical Education, City University of New York Medical School, New York, New York (R.K., M.C., S.G., Z.Y.G., K.V.N., K.K.); School of Pharmacy Health Science Campus, University of Waterloo, Waterloo, Ontario, Canada (P.P.N.R.); and Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada (C.A.V.-M.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mitali Chattopadhyay
Department of Physiology, Pharmacology, and Neuroscience, Sophie Davis School of Biomedical Education, City University of New York Medical School, New York, New York (R.K., M.C., S.G., Z.Y.G., K.V.N., K.K.); School of Pharmacy Health Science Campus, University of Waterloo, Waterloo, Ontario, Canada (P.P.N.R.); and Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada (C.A.V.-M.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Satindra Goswami
Department of Physiology, Pharmacology, and Neuroscience, Sophie Davis School of Biomedical Education, City University of New York Medical School, New York, New York (R.K., M.C., S.G., Z.Y.G., K.V.N., K.K.); School of Pharmacy Health Science Campus, University of Waterloo, Waterloo, Ontario, Canada (P.P.N.R.); and Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada (C.A.V.-M.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zong Yuan Gan
Department of Physiology, Pharmacology, and Neuroscience, Sophie Davis School of Biomedical Education, City University of New York Medical School, New York, New York (R.K., M.C., S.G., Z.Y.G., K.V.N., K.K.); School of Pharmacy Health Science Campus, University of Waterloo, Waterloo, Ontario, Canada (P.P.N.R.); and Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada (C.A.V.-M.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Praveen P. N. Rao
Department of Physiology, Pharmacology, and Neuroscience, Sophie Davis School of Biomedical Education, City University of New York Medical School, New York, New York (R.K., M.C., S.G., Z.Y.G., K.V.N., K.K.); School of Pharmacy Health Science Campus, University of Waterloo, Waterloo, Ontario, Canada (P.P.N.R.); and Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada (C.A.V.-M.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kamran V. Nia
Department of Physiology, Pharmacology, and Neuroscience, Sophie Davis School of Biomedical Education, City University of New York Medical School, New York, New York (R.K., M.C., S.G., Z.Y.G., K.V.N., K.K.); School of Pharmacy Health Science Campus, University of Waterloo, Waterloo, Ontario, Canada (P.P.N.R.); and Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada (C.A.V.-M.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Carlos A. Velázquez-Martínez
Department of Physiology, Pharmacology, and Neuroscience, Sophie Davis School of Biomedical Education, City University of New York Medical School, New York, New York (R.K., M.C., S.G., Z.Y.G., K.V.N., K.K.); School of Pharmacy Health Science Campus, University of Waterloo, Waterloo, Ontario, Canada (P.P.N.R.); and Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada (C.A.V.-M.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Khosrow Kashfi
Department of Physiology, Pharmacology, and Neuroscience, Sophie Davis School of Biomedical Education, City University of New York Medical School, New York, New York (R.K., M.C., S.G., Z.Y.G., K.V.N., K.K.); School of Pharmacy Health Science Campus, University of Waterloo, Waterloo, Ontario, Canada (P.P.N.R.); and Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada (C.A.V.-M.)
  • 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

We compared the differential effects of positional isomers of acetylsalicylic acid (o-ASA, m-ASA, and p-ASA) on cyclooxygenase (COX) inhibition, gastric prostaglandin E2 (PGE2), malondialdehyde, tumor necrosis factor-alpha (TNF-α) levels, superoxide dismutase (SOD) activity, human adenocarcinoma colon cancer cell growth inhibition, cell proliferation, apoptosis, and cell-cycle progression. We also evaluated the gastric toxicity exerted by ASA isomers. All ASA isomers inhibit COX enzymes, but only the o-ASA exerted an irreversible inhibitory profile. We did not observe a significant difference between ASA isomers in their ability to decrease the in vivo synthesis of PGE2 and SOD activity. Furthermore, all isomers increased the levels of gastric and TNF-α when administered orally at equimolar doses. We observed a dose-dependent cell growth inhibitory effect; the order of potency was p-ASA > m-ASA ≈ o-ASA. There was a dose-dependent decrease in cell proliferation and an increase in apoptosis, with a concomitant Go/G1 arrest. The ulcerogenic profile of the three ASA isomers showed a significant difference between o-ASA (aspirin) and its two positional isomers when administered orally at equimolar doses (1 mmol/kg); the ulcer index (UI) for o-ASA indicated extensive mucosal injury (UI = 38), whereas m-ASA and p-ASA produced a significantly decreased toxic response (UI = 12 and 8, respectively) under the same experimental conditions. These results suggest that the three positional isomers of ASA exert practically the same biologic profile in vitro and in vivo but showed different safety profiles. The mechanism of gastric ulcer formation exerted by aspirin and its two isomers warrants a more detailed and thorough investigation.

Footnotes

    • Received November 19, 2012.
    • Accepted January 8, 2013.
  • This work was supported in part by the National Institutes of Health National Cancer Institute through a subcontract from ThermoFisher [Contract #FBS-43312-26]; and by the National Institutes of Health [Grant R24 DA018055].

  • dx.doi.org/10.1124/jpet.112.201970.

  • Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET 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

Journal of Pharmacology and Experimental Therapeutics: 345 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 345, Issue 1
1 Apr 2013
  • 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 Journal of Pharmacology and Experimental Therapeutics 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.
Positional Isomers of Aspirin Are Equally Potent in Inhibiting Colon Cancer Cell Growth: Differences in Mode of Cyclooxygenase Inhibition
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleInflammation, Immunopharmacology, and Asthma

Differential Modes of COX Inhibition by Isomers of Aspirin

Ravinder Kodela, Mitali Chattopadhyay, Satindra Goswami, Zong Yuan Gan, Praveen P. N. Rao, Kamran V. Nia, Carlos A. Velázquez-Martínez and Khosrow Kashfi
Journal of Pharmacology and Experimental Therapeutics April 1, 2013, 345 (1) 85-94; DOI: https://doi.org/10.1124/jpet.112.201970

Citation Manager Formats

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

Share
Research ArticleInflammation, Immunopharmacology, and Asthma

Differential Modes of COX Inhibition by Isomers of Aspirin

Ravinder Kodela, Mitali Chattopadhyay, Satindra Goswami, Zong Yuan Gan, Praveen P. N. Rao, Kamran V. Nia, Carlos A. Velázquez-Martínez and Khosrow Kashfi
Journal of Pharmacology and Experimental Therapeutics April 1, 2013, 345 (1) 85-94; DOI: https://doi.org/10.1124/jpet.112.201970
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
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Expression of PAR2 in iKera to Model Atopic Dermatitis
  • PK/PD of Dexamethasone in LPS-Challenged Rats
  • Cholesterol Esterification and Acute Lung Injury
Show more INFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA

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 JPET
  • 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
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

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