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  • Title: Inhibition of proteasome activity sensitizes human granulosa tumor cells to TRAIL-induced cell death.
    Author: Woods DC, Liu HK, Nishi Y, Yanase T, Johnson AL.
    Journal: Cancer Lett; 2008 Feb 18; 260(1-2):20-7. PubMed ID: 18031928.
    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.
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