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Inhibition of Glutathione and Thioredoxin Metabolism Enhances Sensitivity to Perifosine in Head and Neck Cancer Cells
Joint Authors
Parsons, Arlene D.
Orcutt, Kevin P.
Fath, Melissa A.
Spitz, Douglas R.
Foster, Katherine A.
Simons, Andrean L.
Source
Issue
Vol. 2009, Issue 2009 (31 Dec. 2009), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2009-09-02
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
The hypothesis that the Akt inhibitor, perifosine (PER), combined with inhibitors of glutathione (GSH) and thioredoxin (Trx) metabolism will induce cytotoxicity via metabolic oxidative stress in human head and neck cancer (HNSCC) cells was tested.
PER induced increases in glutathione disulfide (%GSSG) in FaDu, Cal-27, and SCC-25 HNSCCs as well as causing significant clonogenic cell killing in FaDu and Cal-27, which was suppressed by simultaneous treatment with N-acetylcysteine (NAC).
An inhibitor of GSH synthesis, buthionine sulfoximine (BSO), sensitized Cal-27 and SCC-25 cells to PER-induced clonogenic killing as well as decreased total GSH and increased %GSSG.
Additionally, inhibition of thioredoxin reductase activity (TrxRed) with auranofin (AUR) was able to induce PER sensitization in SCC-25 cells that were initially refractory to PER.
These results support the conclusion that PER induces oxidative stress and clonogenic killing in HNSCC cells that is enhanced with inhibitors of GSH and Trx metabolism.
American Psychological Association (APA)
Simons, Andrean L.& Parsons, Arlene D.& Foster, Katherine A.& Orcutt, Kevin P.& Fath, Melissa A.& Spitz, Douglas R.. 2009. Inhibition of Glutathione and Thioredoxin Metabolism Enhances Sensitivity to Perifosine in Head and Neck Cancer Cells. Journal of Oncology،Vol. 2009, no. 2009, pp.1-10.
https://search.emarefa.net/detail/BIM-478183
Modern Language Association (MLA)
Simons, Andrean L.…[et al.]. Inhibition of Glutathione and Thioredoxin Metabolism Enhances Sensitivity to Perifosine in Head and Neck Cancer Cells. Journal of Oncology No. 2009 (2009), pp.1-10.
https://search.emarefa.net/detail/BIM-478183
American Medical Association (AMA)
Simons, Andrean L.& Parsons, Arlene D.& Foster, Katherine A.& Orcutt, Kevin P.& Fath, Melissa A.& Spitz, Douglas R.. Inhibition of Glutathione and Thioredoxin Metabolism Enhances Sensitivity to Perifosine in Head and Neck Cancer Cells. Journal of Oncology. 2009. Vol. 2009, no. 2009, pp.1-10.
https://search.emarefa.net/detail/BIM-478183
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-478183