Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	IAP antagonists Birinapant and AT-406 efficiently synergise with either TRAIL, BRAF, or BCL-2 inhibitors to sensitise BRAFV600E colorectal tumour cells to apoptosis
Δημιουργός/Συγγραφέας:	Perimenis P. Galaris A. Voulgari A. Prassa M. [EL] Πίντζας, Αλέξανδρος[EN] Pintzas, Alexander
Εκδότης:	BioMed Central Ltd.
Ημερομηνία:	2016
Γλώσσα:	Αγγλικά
ISSN:	1471-2407
DOI:	10.1186/s12885-016-2606-5
Άλλο:	PubMed ID: 27520705
Περίληψη:	Background: High expression levels of Inhibitors of Apoptosis Proteins (IAPs) have been correlated with poor cancer prognosis and block the cell death pathway by interfering with caspase activation. SMAC-mimetics are small-molecule inhibitors of IAPs that mimic the endogenous SMAC and promote the induction of cell death by neutralizing IAPs. Methods: In this study, anti-tumour activity of new SMAC-mimetics Birinapant and AT-406 is evaluated against colorectal adenocarcinoma cells and IAP cross-talk with either oncogenic BRAF or BCL-2, or with the TRAIL are further exploited towards rational combined protocols. Results: It is shown that pre-treatment of SMAC-mimetics followed by their combined treatment with BRAF inhibitors can decrease cell viability, migration and can very efficiently sensitize colorectal tumour cells to apoptosis. Moreover, co-treatment of TRAIL with SMAC-mimetics can efficiently sensitize resistant tumour cells to apoptosis synergistically, as shown by median effect analysis. Finally, Birinapant and AT-406 can synergise with BCL-2 inhibitor ABT-199 to reduce viability of adenocarcinoma cells with high BCL-2 expression. Conclusions: Proposed synergistic rational anticancer combined protocols of IAP antagonists Birinapant and AT-406 in 2D and 3D cultures can be later further exploited in vivo, from precision tumour biology to precision medical oncology.
Τίτλος πηγής δημοσίευσης:	BMC Cancer
Τόμος/Κεφάλαιο:	16
Τεύχος:	1
Θεματική Κατηγορία:	[EL] Βιολογία (Γενικά)[EN] Biology (General)
Λέξεις-Κλειδιά:	BCL2 inhibitors BRAF inhibitors IAP antagonists Overcome resistance in colorectal cancer cells Synergistic treatments TRAIL
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Κάτοχος πνευματικών δικαιωμάτων:	© 2016 The Author(s).
Όροι και προϋποθέσεις δικαιωμάτων:	All Open Access, Gold, Green
Σημειώσεις:	11SYN-1-485, MIS 447985. This work was supported by grants from the General Secretariat of Research and Technology of Greece (GSRT) SINERGASIA “THERACAN” 11SYN-1-485 and KRIPIS “STHENOS” MIS 447985.
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο