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

Kornelia Edes, Pamela Cassidy, Paul J. Shami, Philip J. Moos

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Background: 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. Methodology: 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. Conclusions/Significance:In cells with attenuated endogenous thioredoxin reductase 1, a stably integrated selenocysteinedeficient 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 demonstrated enhanced cytotoxicity when thioredoxin reductase 1 was knocked-down; however, the effect was more pronounced with the nitric oxide prodrug. These results are consistent with the hypothesis that attenuation of the thioredoxin-system can promote apoptosis in a nitric oxide-dependent manner.

Original languageEnglish (US)
Article numbere8786
JournalPloS one
Issue number1
StatePublished - Jan 20 2010
Externally publishedYes

ASJC Scopus subject areas

  • General


Dive into the research topics of 'JS-K, a nitric oxide prodrug, has enhanced cytotoxicity in colon cancer cells with knockdown of thioredoxin reductase 1'. Together they form a unique fingerprint.

Cite this