Inhibition of proteasome activity sensitizes human granulosa tumor cells to TRAIL-induced cell death

Dori C. Woods, Han Ken Liu, Yoshihiro Nishi, Toshihiko Yanase, Alan Leslie Johnson

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Human granulosa tumor cell (GCT) lines (KGN and COV434) were utilized to establish the combinatorial effects of TRAIL treatment and a proteasome inhibitor on cell viability, in vitro. TRAIL induced a slight, but consistent, decrease in viability for both cell lines, and pharmacologic inhibition of proteasome activity, using Z-LLF-CHO (Z-LLF), synergistically enhanced TRAIL-induced loss of viability. This enhanced sensitization was associated with the up-regulation of a TRAIL receptor, DR5, and pro-apoptotic Bax. Targeted reduction of p53 expression revealed that the ability of Z-LLF to enhance DR5 and Bax expression occurs independent of p53 activity. These studies underscore the potential to develop targeted treatments for GCTs using established cell lines.

Original languageEnglish (US)
Pages (from-to)20-27
Number of pages8
JournalCancer Letters
Volume260
Issue number1-2
DOIs
StatePublished - Feb 18 2008

Fingerprint

Granulosa Cell Tumor
Proteasome Endopeptidase Complex
Human Activities
Cell Death
TNF-Related Apoptosis-Inducing Ligand Receptors
Cell Line
Proteasome Inhibitors
Tumor Cell Line
Cell Survival
Up-Regulation
In Vitro Techniques
N-benzyloxycarbonyl-leucyl-leucyl-phenylalaninal

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Woods, Dori C. ; Liu, Han Ken ; Nishi, Yoshihiro ; Yanase, Toshihiko ; Johnson, Alan Leslie. / Inhibition of proteasome activity sensitizes human granulosa tumor cells to TRAIL-induced cell death. In: Cancer Letters. 2008 ; Vol. 260, No. 1-2. pp. 20-27.
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Inhibition of proteasome activity sensitizes human granulosa tumor cells to TRAIL-induced cell death. / Woods, Dori C.; Liu, Han Ken; Nishi, Yoshihiro; Yanase, Toshihiko; Johnson, Alan Leslie.

In: Cancer Letters, Vol. 260, No. 1-2, 18.02.2008, p. 20-27.

Research output: Contribution to journalArticle

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AU - Johnson, Alan Leslie

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AB - Human granulosa tumor cell (GCT) lines (KGN and COV434) were utilized to establish the combinatorial effects of TRAIL treatment and a proteasome inhibitor on cell viability, in vitro. TRAIL induced a slight, but consistent, decrease in viability for both cell lines, and pharmacologic inhibition of proteasome activity, using Z-LLF-CHO (Z-LLF), synergistically enhanced TRAIL-induced loss of viability. This enhanced sensitization was associated with the up-regulation of a TRAIL receptor, DR5, and pro-apoptotic Bax. Targeted reduction of p53 expression revealed that the ability of Z-LLF to enhance DR5 and Bax expression occurs independent of p53 activity. These studies underscore the potential to develop targeted treatments for GCTs using established cell lines.

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