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
Abstract

Alterations in glutathione and glutathione-related enzymes in a multidrug-resistant small cell lung cancer cell line.

S P Cole, H F Downes, S E Mirski and D J Clements
Molecular Pharmacology February 1990, 37 (2) 192-197;
S P Cole
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
H F Downes
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
S E Mirski
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
D J Clements
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

H69AR is a multidrug-resistant small cell lung cancer cell line derived from a drug-sensitive cell line, H69, by selection in doxorubicin. It is cross-resistant to a wide variety of natural product-type antineoplastic agents but does not overexpress P-glycoprotein. In the present study, the levels of GSH and GSH-related enzymes in the H69AR cell line were determined and compared with those found in H69 cells. Unlike other drug-resistant cell lines, GSH levels were diminished 6-fold in H69AR cells (0.67 +/- 0.28 microgram/mg of protein), compared with H69 cells (4.23 +/- 1.17 micrograms/mg of protein) (p less than 0.01). This unusually low level of GSH may explain the pronounced collateral sensitivity of H69AR cells to buthionine sulfoximine (BSO), an inhibitor of the rate-limiting enzyme in GSH biosynthesis (ID50 of 4.4 microM BSO for H69AR cells versus ID50 of 300 microM BSO for H69 cells). BSO did not enhance doxorubicin cytotoxicity in the H69AR cell line, despite further depletion of GSH. GSH-reductase (EC 1.6.4.2) activity was elevated 2-fold in H69AR cells, compared with sensitive H69 cells (75.34 +/- 14.94 versus 38.62 +/- 5.06 nmol of NADPH/min/mg of protein) (p less than 0.05). Both selenium-dependent and -independent GSH-peroxidase (EC 1.11.1.9) activities were unchanged in the resistant H69AR cell line, compared with its parent cell line. gamma-Glutamyl transpeptidase (EC 2.3.2.2) activity was 5-fold elevated in H69AR cells, compared with H69 cells (2.50 +/- 0.44 versus 0.46 +/- 0.21 nmol of p-nitroaniline/min/mg of protein) (p less than 0.01), whereas GSH-S-transferase (EC 2.5.1.18) activity was 10-fold higher (201.98 +/- 43.62 versus 19.77 +/- 1.72 nmol of 1-chloro-2,4-dinitrobenzene/min/mg of protein in H69AR and H69 cells, respectively) (p less than 0.01). The GSH-S-transferases from both cell lines were purified by affinity chromatography and immunoblot analysis identified the GSH-S-transferases as belonging to the anionic pi class. GSH-S-transferases from the mu or alpha classes were not detectable in either cell line. In conclusion, marked differences in GSH levels and the activities of three of four GSH-related enzymes were observed between the multidrug-resistant H69AR cell line and its parent cell line. Further study is required to determine whether these changes are causally related to the development of drug resistance in this model system.

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
Vol. 37, Issue 2
1 Feb 1990
  • Table of Contents
  • Table of Contents (PDF)
  • 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.
Alterations in glutathione and glutathione-related enzymes in a multidrug-resistant small cell lung cancer cell line.
(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
Abstract

Alterations in glutathione and glutathione-related enzymes in a multidrug-resistant small cell lung cancer cell line.

S P Cole, H F Downes, S E Mirski and D J Clements
Molecular Pharmacology February 1, 1990, 37 (2) 192-197;

Citation Manager Formats

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

Share
Abstract

Alterations in glutathione and glutathione-related enzymes in a multidrug-resistant small cell lung cancer cell line.

S P Cole, H F Downes, S E Mirski and D J Clements
Molecular Pharmacology February 1, 1990, 37 (2) 192-197;
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
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

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