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

Dori C. Woods; Han Ken Liu; Yoshihiro Nishi; Toshihiko Yanase; A. L. Johnson

doi:10.1016/j.canlet.2007.10.016

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

Dori C. Woods, Han Ken Liu, Yoshihiro Nishi, Toshihiko Yanase, A. L. Johnson

Animal Science

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

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 language	English (US)
Pages (from-to)	20-27
Number of pages	8
Journal	Cancer Letters
Volume	260
Issue number	1-2
DOIs	https://doi.org/10.1016/j.canlet.2007.10.016
State	Published - Feb 18 2008

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.canlet.2007.10.016

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title = "Inhibition of proteasome activity sensitizes human granulosa tumor cells to TRAIL-induced cell death",

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.",

author = "Woods, {Dori C.} and Liu, {Han Ken} and Yoshihiro Nishi and Toshihiko Yanase and Johnson, {A. L.}",

note = "Funding Information: Research was supported by grants from the United States Department of Defense (DAMD17-03-1-0206) and the University of Notre Dame Walther Cancer Research Center.",

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doi = "10.1016/j.canlet.2007.10.016",

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AU - Woods, Dori C.

AU - Liu, Han Ken

AU - Nishi, Yoshihiro

AU - Yanase, Toshihiko

AU - Johnson, A. L.

N1 - Funding Information: Research was supported by grants from the United States Department of Defense (DAMD17-03-1-0206) and the University of Notre Dame Walther Cancer Research Center.

PY - 2008/2/18

Y1 - 2008/2/18

N2 - 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.

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

Abstract

All Science Journal Classification (ASJC) codes

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