Qualified type:	Scientific journal article
Title:	DPS-2: A Novel Dual MEK/ERK and PI3K/AKT Pathway Inhibitor with Powerful Ex Vivo and In Vivo Anticancer Properties
Creator:	Goulielmaki M. Assimomytis N. Rozanc J. Taki E. Christodoulou I. Alexopoulos L.G. [EL] Ζουμπουρλής, Βασίλης[EN] Zoumpourlis, Vassilis [EL] Πίντζας, Αλέξανδρος[EN] Pintzas, Alexander [EL] Παπαχατζής, Δημήτρης Π.[EN] Papahatjis, Demetris P.
Publisher:	Neoplasia Press
Date:	2019
Language:	English
ISSN:	1936-5233
DOI:	10.1016/j.tranon.2019.04.005
Abstract:	Development of novel bioactive compounds against KRAS and/or BRAF mutant colorectal cancer (CRC)is currently an urgent need in oncology. In addition, single or multitarget kinase inhibitors against MEK/ERK and PI3K/AKT pathways are of potential therapeutic advantage. A new compound based on the benzothiophene nucleus was synthesized, based on previous important outcomes on other pharmaceutical preparations, to be tested as potential anticancer agent. Treatments by 2-5 μM DPS-2 of several CRC and melanoma cell lines bearing either BRAF or KRAS mutations have shown a remarkable effect on cell viability in 2D and 3D cultures. More detailed analysis has shown that DPS-2 can kill cancer cells by apoptosis, reducing at the same time their autophagy properties. After testing activities of several signaling pathways, the compound was found to have a dual inhibition of two major proliferative/survival pathways, MEK/ERK and PI3K/AKT, in both CRC and melanoma, thus providing a mechanistic evidence for its potent anticancer activity. Antitumor activity of DPS-2 was further validated in vivo, as DPS-2 treatment of mouse xenografts of Colo-205 colorectal cancer cells remarkably reduced their tumor formation properties. Our findings suggest that DPS-2 has significant anti-KRAS/ anti-BRAF mutant CRC activity in preclinical models, potentially providing a novel treatment strategy for these difficult-to-treat tumors, which needs to be further exploited.
Reference title:	Translational Oncology
Volume/Chapter:	12
Issue:	7
Pages:	932-950
Subject:	[EL] Βιολογία (Γενικά)[EN] Biology (General)
Peer review:	Yes
Rights holder:	© 2019 The Authors
Rights terms of use:	All Open Access, Gold, Green
Notes:	Horizon 2020 Framework Programme, H2020: 642295; European Commission, EC: MIS 447985; General Secretariat for Research and Technology, GSRT: 2400, MIS 5002398; European Regional Development Fund, FEDER; Hellenic Foundation for Research and Innovation, HFRI. This work was supported by Greece and the European Regional Development Fund of the European Union under the O.P. Competitiveness, Entrepreneurship and Innovation NSRF 2007-2013 and the Regional Operational Program of Attica (STHENOS project MIS 447985 within GSRT'S KRIPIS) and the grant EU Horizon 2020-Mel-Plex (grant no. 642295 ). The salary of the Phd candidate M. G. was supported by the Hellenic Foundation for Research and Innovation (HFRI) and the General Secretariat for Research and Technology (GSRT) under the HFRI PhD Fellowship grant (GA no. 2400 ). We also acknowledge support of this work by the project “STHENOS-b'' (MIS 5002398), which is funded by the Operational Programme "Competitiveness, Entrepreneurship and Innovation" (NSRF 2014-2020) and co-financed by Greece and the EU (European Regional Development Fund).
Appears in Collections:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο