[Development of anti cancer drugs targeted on Fas-mediated apoptosis signal].

Abstract

The elimination of tumor cells by cytotoxic T lymphocytes (CTLs) is, in part, executed by inducing apoptosis through the cell surface antigen Fas on the target cells. There are many cancer cells that resist Fas-mediated apoptosis. To elucidate the mechanism of this resistance is very important to understand the process of tumor development. We focused on FAP-1 (Fas-associated phos phatase-1), a negative regulator of Fas-mediated apoptosis. The expression of FAP-1 was detected in many colon cancer cell lines. On the other hand no FAP-1 expression was detected in the normal colon tissue. We have found that the tri-peptide of Fas C-terminus inhibited the binding of Fas and FAP-1 in vitro. Microinjection of the tri peptide (Ac SLV) could induce Fas-mediated apoptosis in the DLD 1 human colon cancer cell line that was resistant to anti-Fas-antibody. These findings suggest that the interaction of Fas and FAP-1 has a very important role in Fas-mediated apoptosis signal transduction. The inhibition of the Fas/ FAP-1 binding will provide a good target to develop anti-cancer drugs.

• Authors: M Takahashi, S Kataoka
• Journal: Gan to kagaku ryoho. Cancer & chemotherapy (Gan To Kagaku Ryoho) Vol. 24 Issue 2 Pg. 222-8 (Jan 1997) ISSN: 0385-0684 [Print] Japan
• PMID: 9030235 (Publication Type: Journal Article, Review)

Chemical References

• Antineoplastic Agents
• fas Receptor
• Protein Tyrosine Phosphatases

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Colonic Neoplasms (metabolism, pathology)
• Humans
• Protein Tyrosine Phosphatases (metabolism, physiology)
• Signal Transduction
• T-Lymphocytes, Cytotoxic (immunology)
• fas Receptor (physiology)