Tetrapeptide DEVD-aldehyde or YVAD-chloromethylketone inhibits Fas/Apo-1 (CD95)-mediated apoptosis in renal-cell-cancer cells
✍ Scribed by Yoshihiko Tomita; Takashi Kawasaki; Vladimir Bilim; Masayuki Takeda; Kota Takahashi
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- French
- Weight
- 500 KB
- Volume
- 68
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
The apoptotic machinery has been intensively investigated, and interleukin-I -beta-converting enzyme (ICE) and its homologs directly mediate apoptosis by means of their unique protease activity. Fas/Apol (CD95). a member of the TNFreceptor family, mediates apoptosis by binding to its ligand, which is mainly expressed on lymphocytes. Here, we investigated the expression and function of both molecules in renalcell cancer (RCC). The expression of Fas was examined in 6 RCC cell lines by immunoblotting and all of them expressed Fas. ICE and CPP32/YAMA were also identified among the cell lines. We earlier examined ACHN cells expressing low levels of BCL-2, as well as KRC/Y cells with high levels of BCL-2. Here, we found that the anti-Fas monoclonal antibody, CH-I I, induced apoptosis in a dose-dependent fashion more remarkably in ACHN cells. Pre-incubation with the tetrapeptide WAD-chloromethylketone or DEVD-aldehyde inhibited Fas-mediated apoptosis. These findings suggest that, in RCC, apoptosis is induced by lymphocytes bearing Fas-L, and that it is achieved through the proteolytic action of CPP32/YAMA and/or ICE, or another member of the ICE/ced-3 p r o t w e family.