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Updated: Feb 23, 2026
Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
Published on: August 7, 2018
Alkynyl gold(I) complex triggers necroptosis via ROS generation in colorectal carcinoma cells
Inés Mármol1, María Virumbrales-Muñoz2, Javier Quero1
1Department of Pharmacology and Physiology, University of Zaragoza, CIBERobn, IIS Aragón, IA2, Zaragoza, Spain.
Abstract:
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.
Insights
A novel gold(I) complex, [Au(CC-2-NC5H4)(PTA)], effectively induces necroptosis in colorectal cancer cells by disrupting mitochondrial function. This compound shows promise as an alternative cancer therapy for apoptosis-resistant tumors.
Area of Science:
- Medicinal Chemistry
- Cancer Biology
- Pharmacology
Background:
- Apoptosis-resistant tumors present a significant challenge in cancer therapy, driving the need for alternative cell death induction strategies.
- Necroptosis, a distinct form of programmed cell death, offers therapeutic potential against apoptosis-resistant cancers, despite associated inflammatory effects.
Purpose of the Study:
- To synthesize and evaluate a novel alkynyl gold(I) complex, [Au(CC-2-NC5H4)(PTA)], for its anticancer efficacy.
- To elucidate the mechanism of action of the gold complex in inducing cell death in colorectal cancer.
Main Methods:
- Synthesis of the alkynyl gold(I) complex [Au(CC-2-NC5H4)(PTA)].
- Anticancer activity testing on the colorectal adenocarcinoma Caco-2 cell line and 3D spheroid models.
- Investigation of the mechanism of cell death induction, including mitochondrial function, ROS production, and key signaling pathways (TNF-α, TNFR1, RIP1, NF-κB).
Main Results:
- The gold complex [Au(CC-2-NC5H4)(PTA)] was successfully synthesized and demonstrated anticancer effects.
- The compound induces necroptosis by entering mitochondria, disrupting function, increasing ROS production, and activating the TNF-α/TNFR1/RIP1/NF-κB pathway.
- Antitumor potential was confirmed in a 3D cancer spheroid model.
Conclusions:
- Gold(I) complexes can be engineered to induce necroptosis, offering a new therapeutic avenue.
- [Au(CC-2-NC5H4)(PTA)] represents a promising alternative to conventional chemotherapy for apoptosis-resistant colorectal cancers.
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