Home | My Profile | Contact Us
Research Trends Products  |   order gateway  |   author gateway  |   editor gateway  
Register | Forgot Password

Author Resources
 Author Gateway
 Article submission guidelines

Editor Resources
 Editor/Referee Gateway

 Regional Subscription Agents/Distributors
Current Topics in Pharmacology   Volumes    Volume 5 
FAS/FASL system and drug-induced apoptosis: are they linked to each other?
Cristina Goso, Carlo Alberto Maggi
Pages: 155 - 166
Number of pages: 12
Current Topics in Pharmacology
Volume 5 

Copyright © 2000 Research Trends. All rights reserved


Fas/Fas ligand (FasL) system has been demonstrated to be a key factor in the induction of apoptotic cell death. Death signal is initiated through the engagement of the Fas receptor by FasL and proceeds with the activation of an intracellular cascade of biochemical events culminating in the cleavage of specific substrates by the final executioners of apoptosis, the caspase enzymes.

The possible role of the Fas/FasL pathway in the induction of the apoptotic cell death elicited by cytotoxic drugs has been an argument of active research and scientific debate, since the demonstration that cytotoxic drugs, like cisplatinum and doxorubicin, induce the expression of both Fas receptor and PasL in cancer cells.

In several tumour cell lines blockade of the drug-induced Fas receptor with an antagonistic antibody does not inhibit drug-induced apoptosis. On the other hand, drug-induced apoptosis can be almost completely inhibited by caspase inhibitors. Not only caspases, but also other intracellular mediators of the death receptor apoptotic pathways are activated (up or down regulated, according to their pro or anti-apoptotic action) following drug exposure.

Two conclusions can be drawn: 1) Fas activation is not mandatory for drug-induced apoptosis and 2) different stimuli triggering apoptosis converge during the execution phase on some common final steps.

The expression of Fas receptor induced by DNA damaging agents can be fully functional. Engagement of the receptor determines a further increase in the apoptotic response induced by drugs, thus enhancing the total cytotoxic effect. Obviously, synergistic interaction between FasL and DNA damaging drugs requires a functional receptor and an intact signal transduction pathway.

Agents able to induce a functional Fas receptor accumulation can therefore sensitise tumour cells to death receptor-induced apoptosis, and thus open the interesting new therapeutic perspective of using Fas agonists to potentiate the action of cytotoxic drugs.

Buy this Article


Buy this article
Buy this volume
Subscribe to this title
Shopping Cart

Quick Links
Search Products
Browse in Alphabetical Order : Journals
Browse by Subject Classification : Journals

Ordering Information Ordering Information
Downloadable forms Downloadable Forms