Alkynyl gold(I) complex triggers necroptosis via ROS generation in colorectal carcinoma cells

作者：Marmol Ines; Virumbrales Munoz Maria; Quero Javier; Sanchez de Diego Cristina; Fernandez Luis; Ochoa Ignacio; Cerrada Elena^*; Jesus Rodriguez Yoldi Ma

来源：Journal of Inorganic Biochemistry, 2017, 176: 123-133.

DOI：10.1016/j.jinorgbio.2017.08.020

• Gold complex
• Cancer
• Necroptosis
• ROS (Reactive Oxigen Species)
• Caco-2 cells

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.

• 出版日期2017-11