Alkynyl gold(I) complex triggers necroptosis via ROS generation in colorectal carcinoma cells
| العنوان: | Alkynyl gold(I) complex triggers necroptosis via ROS generation in colorectal carcinoma cells |
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| المؤلفون: | Cristina Sánchez-de-Diego, Ignacio Ochoa, Mª. Jesús Rodríguez Yoldi, María Virumbrales-Muñoz, Luis J. Fernández, Javier Quero, Inés Mármol, Elena Cerrada |
| المساهمون: | Ministerio de Economía y Competitividad (España), Diputación General de Aragón, Ministerio de Educación, Cultura y Deporte (España) |
| المصدر: | Zaguán. Repositorio Digital de la Universidad de Zaragoza instname Digital.CSIC. Repositorio Institucional del CSIC |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Programmed cell death, Necroptosis, Antineoplastic Agents, Mitochondrion, Adenocarcinoma, 010402 general chemistry, 01 natural sciences, Biochemistry, Inorganic Chemistry, Necrosis, Coordination Complexes, medicine, Humans, Receptor, Caco-2 cells, Gold complex, Cancer, ROS (Reactive Oxigen Species), 010405 organic chemistry, Chemistry, 0104 chemical sciences, Mechanism of action, Caco-2, Cell culture, Apoptosis, Immunology, Cancer research, MCF-7 Cells, Gold, medicine.symptom, Drug Screening Assays, Antitumor, Colorectal Neoplasms, Reactive Oxygen Species |
| الوصف: | 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-α (Tumor necrosisfactor α) and TNFR1(Tumor necrosisfactor receptor 1) binding, RIP1(Receptor-Interacting Protein 1) activation and NF-κB (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. We thank The Ministerio de Economia y Competitividad (CTQ2016-75816-C2-1-P and SAF2016-75441-R) and DGA (A-32 and E104) for financial support. MVM acknowledges the Ministerio de Educación, Cultura y Deportes (FPU 12/05640) of the Spanish Government for financial support. |
| وصف الملف: | application/pdf |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::abe0da835b7add38fce608250de226b7Test http://zaguan.unizar.es/record/74851Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....abe0da835b7add38fce608250de226b7 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |