74851 20200324135213.0 doi 10.1016/j.jinorgbio.2017.08.020 sideral 101468 ART-2017-101468 eng Mármol, Inés Universidad de Zaragoza Alkynyl gold(I) complex triggers necroptosis via ROS generation in colorectal carcinoma cells 2017 Access copy available to the general public Unrestricted Given the rise of apoptosis-resistant tumors, there exist a growing interest in developing new drugs capable of inducing different types of cell death to reduce colorectal cancer-related death rates. As apoptosis and necroptosis do not share cellular machinery, necroptosis induction may have a great therapeutic potential on those apoptosis- resistant cancers, despite the inflammatory effects associated with it. We have synthesized an alkynyl gold(I) complex [Au(CC-2-NC5H4)(PTA)] whose anticancer effect was tested on the colorectal adenocarcinoma Caco-2 cell line. With regard to its mechanism of action, this gold complex enters the mitochondria and disrupts its normal function, leading to an increase in ROS production, which triggers necroptosis. Necroptosis induction has been found dependent of TNF-a (Tumor necrosisfactor a) and TNFR1(Tumor necrosisfactor receptor 1) binding, RIP1(Receptor-Interacting Protein 1) activation and NF-¿B (Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells) signaling. Moreover, the antitumor potential of [Au(CC-2-NC5H4)(PTA)] has also been confirmed on the 3D cancer model spheroid. Overall, the obtained data show firstly that gold complexes might have the ability of inducing necroptosis, and secondarily that our compound [Au(CC-2-NC5H4)(PTA)] is an interesting alternative to current chemotherapy drugs in cases of apoptosis resistance. info:eu-repo/grantAgreement/ES/DGA/A32 info:eu-repo/grantAgreement/ES/DGA/E104 info:eu-repo/grantAgreement/ES/MEC/FPU12-05640 info:eu-repo/grantAgreement/ES/MINECO/CTQ2016-75816-C2-1-P info:eu-repo/grantAgreement/ES/MINECO/SAF2016-75441-R info:eu-repo/semantics/openAccess by-nc-nd http://creativecommons.org/licenses/by-nc-nd/3.0/es/ 3.063 2017 CHEMISTRY, INORGANIC & NUCLEAR 10 / 45 = 0.222 2017 Q1 T1 BIOCHEMISTRY & MOLECULAR BIOLOGY 137 / 292 = 0.469 2017 Q2 T2 0.743 2017 Inorganic Chemistry 2017 Q2 Biochemistry 2017 Q3 info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion (orcid)0000-0003-3660-8651 Virumbrales-Muñoz, María Universidad de Zaragoza Quero, Javier Sánchez-de-Diego, Cristina (orcid)0000-0001-5376-4440 Fernández, Luis Universidad de Zaragoza (orcid)0000-0003-2410-5678 Ochoa, Ignacio Universidad de Zaragoza (orcid)0000-0003-2457-3674 Cerrada, Elena Universidad de Zaragoza (orcid)0000-0002-3595-7668 Rodriguez-Yoldi, María Jesús Universidad de Zaragoza 2010 760 Universidad de Zaragoza Dpto. Química Inorgánica Área Química Inorgánica 1005 410 Universidad de Zaragoza Dpto. Farmacología y Fisiolog. Área Fisiología 1003 443 Universidad de Zaragoza Dpto. Anatom.Histolog.Humanas Area Histología 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 5004 605 Universidad de Zaragoza Dpto. Ingeniería Mecánica Área Mec.Med.Cont. y Teor.Est. 176 (2017), 123-133 J. inorg. biochem. JOURNAL OF INORGANIC BIOCHEMISTRY 0162-0134 2156266 http://zaguan.unizar.es/record/74851/files/texto_completo.pdf Postprint 34472 http://zaguan.unizar.es/record/74851/files/texto_completo.jpg?subformat=icon icon Postprint oai:zaguan.unizar.es:74851 articulos driver 2020-03-24-10:01:09 ARTICLE