JS-K, a nitric oxide prodrug, has enhanced cytotoxicity in colon cancer cells with knockdown of thioredoxin reductase 1.

PloS One
Kornelia EdesPhilip J Moos

Abstract

The selenoenzyme thioredoxin reductase 1 has a complex role relating to cell growth. It is induced as a component of the cellular response to potentially mutagenic oxidants, but also appears to provide growth advantages to transformed cells by inhibiting apoptosis. In addition, selenocysteine-deficient or alkylated forms of thioredoxin reductase 1 have also demonstrated oxidative, pro-apoptotic activity. Therefore, a greater understanding of the role of thioredoxin reductase in redox initiated apoptotic processes is warranted. The role of thioredoxin reductase 1 in RKO cells was evaluated by attenuating endogenous thioredoxin reductase 1 expression with siRNA and then either inducing a selenium-deficient thioredoxin reductase or treatment with distinct redox challenges including, hydrogen peroxide, an oxidized lipid, 4-hydroxy-2-nonenol, and a nitric oxide donating prodrug. Thioredoxin redox status, cellular viability, and effector caspase activity were measured. In cells with attenuated endogenous thioredoxin reductase 1, a stably integrated selenocysteine-deficient form of the enzyme was induced but did not alter either the thioredoxin redox status or the cellular growth kinetics. The oxidized lipid and the nitric oxide donor...Continue Reading

References

Mar 7, 1996·Biochemical and Biophysical Research Communications·G Spyrou, A Holmgren
Aug 5, 1996·Biochemical and Biophysical Research Communications·E S ArnérA Holmgren
Oct 17, 1998·Molecular and Cellular Biology·E R HofmannD V Kalvakolanu
Dec 16, 1998·Trends in Pharmacological Sciences·S LamasS Moncada
Jan 29, 2000·Journal of Medicinal Chemistry·J E SaavedraL K Keefer
Jul 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·P J MoosF A Fitzpatrick
Jun 8, 2001·The Journal of Biological Chemistry·J E MullallyF A Fitzpatrick
Dec 1, 2001·Free Radical Biology & Medicine·J Nordberg, E S Arnér
Aug 4, 2004·Cancer Chemotherapy and Pharmacology·Dashnamoorthy Ravi, Kumuda C Das
Feb 3, 2005·Cancer Biology & Therapy·John E Biaglow, Richard A Miller
Feb 3, 2005·Nature Reviews. Molecular Cell Biology·Douglas T HessJonathan S Stamler
Oct 27, 2005·Journal of Biochemistry and Molecular Biology·Ki-Mo KimYoung-Myeong Kim
Nov 10, 2005·Journal of the American Chemical Society·Detcho A StoyanovskyValerian E Kagan
Jan 13, 2006·British Journal of Pharmacology·S Moncada, E A Higgs
Jan 18, 2006·International Journal of Radiation Oncology, Biology, Physics·Abby Rosenberg, Susan Knox
Feb 9, 2006·Journal of the American Chemical Society·Jianguo Fang, Arne Holmgren
Feb 17, 2006·The Journal of Biological Chemistry·Seyed Isaac HashemyArne Holmgren
Mar 28, 2006·The Journal of Biological Chemistry·Min-Hyuk YooDolph L Hatfield
Nov 10, 2006·Seminars in Cancer Biology·Elias S J Arnér, Arne Holmgren
Dec 13, 2006·Toxicology and Applied Pharmacology·Xufang WangTongwen Xu
Feb 3, 2007·Expert Opinion on Pharmacotherapy·Gregory M Richards, Minesh P Mehta
Mar 30, 2007·Diabetes Care·Joachim BleysEliseo Guallar
Jun 15, 2007·International Journal of Radiation Oncology, Biology, Physics·Judith M FordSee-Chun Phan
Aug 4, 2007·Clinical Biochemistry·James M MayDeanna J Nelson
Sep 1, 2007·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·William N WilliamDavid J Stewart
Feb 13, 2008·Biochemical and Biophysical Research Communications·Walter H WatsonJeanine C Spielberger
Feb 27, 2008·Archives of Internal Medicine·Joachim BleysEliseo Guallar
Apr 3, 2008·PloS One·Karin AnestålElias S J Arnér
May 24, 2008·Science·Moran BenharJonathan S Stamler

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Citations

Sep 22, 2015·Biochimica Et Biophysica Acta·Moran Benhar
May 3, 2016·The Journal of Clinical Investigation·Moran BenharAndrea Savarino
Feb 8, 2019·Current Protein & Peptide Science·Arunaksharan NarayanankuttyVinayak Narayanankutty

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Methods Mentioned

BETA
caspase assay
Assay

Software Mentioned

BioPORTER
GraphPad InStat

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