Thioredoxin reductase as a novel molecular target for cancer therapy

Phuongmai Nguyen, Rania T. Awwad, Dee Dee K Smart, Douglas R. Spitz, David Gius*

*Corresponding author for this work

Research output: Contribution to journalShort survey

116 Citations (Scopus)

Abstract

Tumor cell proliferation, de-differentiation, and progression depend on a complex combination of altered cell cycle regulation, excessive growth factor pathway activation, and decreased apoptosis. The understanding of these complex mechanisms should lead to the identification of potential targets for therapeutic intervention. Redox-sensitive signaling factors also regulate multiple cellular processes including proliferation, cell cycle, and pro-survival signaling cascades, suggesting their potential as molecular targets for anticancer agents. These observations suggest that redox-sensitive signaling factors may be potential novel molecular markers. We hypothesized that thioredoxin reductase-1 (TR), a component of several redox-regulated pathways, may represent a potential molecular target candidate in response to agents that induce oxidative stress. There have been numerous biological studies over the last decade investigating the cell biological, biochemical, and genetic properties of TR both in culture and in in vivo models. In addition, using a series of permanent cell lines that express either a wild-type TR or a dominant mutant TR gene or a chemical agent that inhibits TR we demonstrated that TR meets most criteria that would identify a molecular target. Based on these results we believe TR is a potential molecular target and discuss potential clinical possibilities.

Original languageEnglish (US)
Pages (from-to)164-174
Number of pages11
JournalCancer Letters
Volume236
Issue number2
DOIs
StatePublished - May 18 2006

Fingerprint

Thioredoxin Reductase 1
Thioredoxin-Disulfide Reductase
Neoplasms
Oxidation-Reduction
Therapeutics
Cell Cycle
Antineoplastic Agents
Molecular Biology
Intercellular Signaling Peptides and Proteins
Oxidative Stress
Cell Proliferation
Apoptosis
Cell Line

Keywords

  • Anticancer agents
  • Molecular targets
  • Thioredoxin reductase

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Nguyen, Phuongmai ; Awwad, Rania T. ; Smart, Dee Dee K ; Spitz, Douglas R. ; Gius, David. / Thioredoxin reductase as a novel molecular target for cancer therapy. In: Cancer Letters. 2006 ; Vol. 236, No. 2. pp. 164-174.
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Thioredoxin reductase as a novel molecular target for cancer therapy. / Nguyen, Phuongmai; Awwad, Rania T.; Smart, Dee Dee K; Spitz, Douglas R.; Gius, David.

In: Cancer Letters, Vol. 236, No. 2, 18.05.2006, p. 164-174.

Research output: Contribution to journalShort survey

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