Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2067/43497
Titolo: XIAP as a Target of New Small Organic Natural Molecules Inducing Human Cancer Cell Death
Autori: Muñoz, Diego
Brucoli, Martina
Zecchini, Silvia
Sandoval-Hernandez, Adrian
Arboleda, Gonzalo
Lopez-Vallejo, Fabian
Delgado, Wilman
Giovarelli, Matteo
Coazzoli, Marco
Catalani, Elisabetta
De Palma, Clara
Perrotta, Cristiana
Cuca, Luis
Clementi, Emilio
Cervia, Davide 
Rivista: CANCERS 
Data pubblicazione: 2019
Abstract: 
X-linked inhibitor of apoptosis protein (XIAP) is an emerging crucial therapeutic target in cancer. We report on the discovery and characterisation of small organic molecules from Piper genus plants exhibiting XIAP antagonism, namely erioquinol, a quinol substituted in the 4-position with an alkenyl group and the alkenylphenols eriopodols A-C. Another isolated compound was originally identified as gibbilimbol B. Erioquinol was the most potent inhibitor of human cancer cell viability when compared with gibbilimbol B and eriopodol A was listed as intermediate. Gibbilimbol B and eriopodol A induced apoptosis through mitochondrial permeabilisation and caspase activation while erioquinol acted on cell fate via caspase-independent/non-apoptotic mechanisms, likely involving mitochondrial dysfunctions and aberrant generation of reactive oxygen species. In silico modelling and molecular approaches suggested that all molecules inhibit XIAP by binding to XIAP-baculoviral IAP repeat domain. This demonstrates a novel aspect of XIAP as a key determinant of tumour control, at the molecular crossroad of caspase-dependent/independent cell death pathway and indicates molecular aspects to develop tumour-effective XIAP antagonists.
URI: http://hdl.handle.net/2067/43497
ISSN: 2072-6694
DOI: 10.3390/cancers11091336
Diritti: Attribution-NonCommercial-NoDerivs 3.0 United States
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