Volume 68, Issue 1 pp. 132-135
Human Cancer

Tetrapeptide DEVD-aldehyde or YVAD-chloromethylketone inhibits Fas/Apo-1 (CD95)-mediated apoptosis in renal-cell-cancer cells

Yoshihiko Tomita

Corresponding Author

Yoshihiko Tomita

Department of Urology, Niigata University School of Medicine, Asahimachi 1, Niigata 951, Japan

Department of Urology. Niigata University School of Medicine, Asahimachi 1, Niigata 951, Japan. Fax: +81-25-229-2258Search for more papers by this author
Takashi Kawasaki

Takashi Kawasaki

Department of Urology, Niigata University School of Medicine, Asahimachi 1, Niigata 951, Japan

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Vladimir Bilim

Vladimir Bilim

Department of Urology, Niigata University School of Medicine, Asahimachi 1, Niigata 951, Japan

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Masayuki Takeda

Masayuki Takeda

Department of Urology, Niigata University School of Medicine, Asahimachi 1, Niigata 951, Japan

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Kota Takahashi

Kota Takahashi

Department of Urology, Niigata University School of Medicine, Asahimachi 1, Niigata 951, Japan

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Abstract

The apoptotic machinery has been intensively investigated, and interleukin-l-beta-converting enzyme (ICE) and its homologs directly mediate apoptosis by means of their unique protease activity. Fas/Apol (CD95), a member of the TNF-receptor 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 renal-cell 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-11, induced apoptosis in a dose-dependent fashion more remarkably in ACHN cells. Pre-incubation with the tetrapeptide YVAD-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 protease family. © 1996 Wiley-Liss, Inc.

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