期刊
JOURNAL OF INORGANIC BIOCHEMISTRY
卷 176, 期 -, 页码 123-133出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2017.08.020
关键词
Gold complex; Cancer; Necroptosis; ROS (Reactive Oxigen Species); Caco-2 cells
资金
- Ministerio de Economia y Competitividad [CTQ2016-75816-C2-1-P, SAF2016-75441-R]
- DGA
- Ministerio de Educacion, Cultura y Deportes of the Spanish Government [FPU 12/05640]
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(C=C-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-alpha (Tumor necrosisfactor alpha) and TNFR1(Tumor necrosisfactor receptor 1) binding, RIP1(Receptor-Interacting Protein 1) activation and NF-kappa 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(CmC-2-NC5H4) (PTA)] is an interesting alternative to current chemotherapy drugs in cases of apoptosis resistance.
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