Increased rate of glutathione synthesis from cystine in drug-resistant MCF-7 cells

Biochemical Pharmacology
M P GamcsikBrandon R Cox

Abstract

The rate of glutathione synthesis was determined in drug-sensitive and -resistant MCF-7 cells by monitoring the rate of label uptake from [3,3'-13C(2)]-cystine using NMR spectroscopy and mass spectrometry. Compared with the wild-type human mammary adenocarcinoma cell line (MCF-7wt), the isotope incorporation rate was increased 1.6-, 2.4-, and 5.3-fold in the etoposide-resistant MCF-7 cell line (MCF-7vp), doxorubicin-resistant MCF-7 cell line (MCF-7adr), and 4-hydroperoxycyclophosphamide-resistant MCF-7 cell line (MCF-7hc), respectively. The increase in glutathione metabolism in the MCF-7hc line correlated with steady-state levels as determined by biochemical assay. In contrast, both the MCF-7vp and MCF-7adr lines showed increased metabolic synthesis of glutathione but displayed lower steady-state levels compared with the MCF-7wt line. The increased synthetic rates of all resistant lines reflected, in part, contributions from the increased activities of both gamma-glutamyltranspeptidase and gamma-glutamylcysteine synthetase. These results emphasize the importance of monitoring glutathione metabolic rates, rather than steady-state levels of enzymes or substrates, for assessing drug resistance.

References

May 1, 1978·Analytical Biochemistry·S T Ohnishi, J K Barr
Jul 31, 1992·Biochemical and Biophysical Research Communications·J A Willis, T Schleich
Dec 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·K H CowanC E Myers
Jan 1, 1993·Advances in Enzyme Regulation·O M ColvinJ Hilton
Aug 21, 1996·Biochimica Et Biophysica Acta·J A Willis, T Schleich
Jun 13, 1998·Journal of the National Cancer Institute·D A ScudieroE A Sausville
Apr 15, 1999·European Journal of Clinical Investigation·A G Hall
Jan 21, 2000·Free Radical Biology & Medicine·W G KirlinD P Jones
Feb 7, 2001·Cancer Chemotherapy and Pharmacology·J L FlowersD J Adams

❮ Previous
Next ❯

Citations

Nov 8, 2003·International Journal of Hematology·Hiroaki GotoShumpei Yokota
Dec 31, 2002·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·G RappaA Lorico
Jun 28, 2008·Nutrition and Cancer·Yihong KaufmannV Suzanne Klimberg
Jan 25, 2003·Anti-cancer Drugs·Peter W GoutMay C Robertson
Aug 17, 2005·Medical Principles and Practice : International Journal of the Kuwait University, Health Science Centre·Y A Luqmani
Feb 16, 2005·Proceedings of the National Academy of Sciences of the United States of America·Ilse KrannerHartwig W Pfeifhofer
Jun 28, 2011·Toxicology and Applied Pharmacology·Chang Seon RyuSang Kyum Kim
Jul 14, 2011·NMR in Biomedicine·Peter E ThelwallMichael P Gamcsik
Jan 26, 2010·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·Kayvan R KeshariJeffrey M Macdonald
Aug 26, 2009·Rapid Communications in Mass Spectrometry : RCM·Ni-Chen ChiangHuan-Tsung Chang
Apr 13, 2007·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Jan Cz DobrowolskiJoanna Sadlej
Nov 17, 2005·Cancer Research·Peter E ThelwallMichael P Gamcsik
Sep 1, 2004·Free Radical Biology & Medicine·Michael P GamcsikKevin K Millis

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.