Skip Navigation



Carcinogenesis Advance Access published online on August 18, 2006
Carcinogenesis, doi:10.1093/carcin/bgl148
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
28/2/465    most recent
bgl148v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Johansson, K.
Right arrow Articles by Morgenstern, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Johansson, K.
Right arrow Articles by Morgenstern, R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org
Received May 31, 2006
Revised August 9, 2006
Accepted August 11, 2006

CARCINOGENESIS

Microsomal glutathione transferase 1 in anti-cancer drug resistance

Katarina Johansson 1 *, Karin Åhlen 1, Rosanna Rinaldi 2, Karin Sahlander 3, Atchasai Siritantikorn 4, and Ralf Morgenstern 1

1 Institute of Environmental Medicine, Division of Biochemical Toxicology, Karolinska Institutet, SE-171 77 Stockholm, Sweden
2 Istituto Scientifico San Raffaele, via Olgettina 58, 20132 Milano, Italy
3 Lung and Allergy Research, Division of Physiology, National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
4 Department of Laboratory Medicine, Faculty of Medicine, Chulalongkorn University, BKK 10330, Thailand

* To whom correspondence should be addressed.
Katarina Johansson, E-mail: katarina.johansson{at}ki.se


  Abstract

Glutathione transferases are often up-regulated in tumors and have been suggested to play an important role in multiple drug resistance in cancer chemotherapy. As a consequence glutathione transferase dependent pro-drugs and inhibitors are being developed. Little is known however on the potential role of membrane bound glutathione transferases in drug resistance despite the fact that detoxication of cytostatic drugs and up-regulation in tumors has been demonstrated. Therefore we have studied the involvement of membrane bound microsomal glutathione transferase 1 (MGST1) in cellular resistance to anti-cancer drugs. As a tool we have developed a cell system utilising MCF7 cells stably overexpressing MGST1. Here, we show for the first time, that MGST1 can protect cells from several cytostatic drugs, chlorambucil, melphalan, and cisplatin in an acute toxicity test (MTT-assay) as well as a long term colony forming efficiency cytotoxicity test. It is of note that these cells do not overexpress multidrug transporters, a prerequisite for protection with certain other glutathione transferases investigated in this system. The cytostatic drugs used comprise both those that are known/predicted to be substrates as well as non-substrates. Thus the mechanism most probably entails both direct detoxication and downstream protection of the cells from oxidative stress.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 JCOHome page
K. Scotlandi, D. Remondini, G. Castellani, M. C. Manara, F. Nardi, L. Cantiani, M. Francesconi, M. Mercuri, A. M. Caccuri, M. Serra, et al.
Overcoming Resistance to Conventional Drugs in Ewing Sarcoma and Identification of Molecular Predictors of Outcome
J. Clin. Oncol., May 1, 2009; 27(13): 2209 - 2216.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.