Colorectal adenocarcinoma is one of the main causes of cancer-related dead and the second most prevalent in Western countries. Treatment involves surgical resection followed by 5-fluoracil-based adjuvant therapy, but although it substantially improves survival, it is associated with side effects that affect overall health and the quality of life. Therefore, it is necessary to develop a novel, less toxic and more efficient therapy to treat this disease. Gold compounds have already been used in medicine as antibacterial drugs, but nowadays are in focus because several studies have demonstrated that organometallic compounds with a coordinated gold atom in the oxidation states +1 and +3 have strong cytotoxicity in different cancer cell lines. Most of these compounds produce cell death by apoptosis but due to the increase of tumors resistant to apoptosis, it is needed new drugs able to induce other forms of cell death. Necroptosis induction may have a great therapeutic potential on those apoptosis-resistant cancers, in spite of the inflammatory effects associated with it. We have synthetized and characterized an alkynyl gold(I) complex *Au(C≡C-2-NC5H4)(PTA)] whose anticancer effect was tested on colorectal adenocarcinoma Caco-2 cell line. With regard to its mechanism of action, this gold complex leads to an increase in ROS production, which triggers necroptosis. Necroptosis induction has been found dependent of TNF-α and TNFR1 binding, RIP1 activation and NF-κB signaling. Thus, this complex could be an interesting alternative to current chemotherapy drugs in cases of apoptosis resistance.

Resumen del trabajo presentado al 14th International Symposium on Applied Bioinorganic Chemistry (ISABC), celebrado en Toulouse (Francia) del 7 al 10 de junio de 2017.

Peer reviewed