New gold(III) complexes TGS 121, 404, and 702 show anti-tumor activity in colitis-induced colorectal cancer: an in vitro and in vivo study

• Published in: Pharmacological reports 2024-02, Vol.76 (1), p.127-139
• Main Authors: Włodarczyk, Jakub, Krajewska, Julia, Talar, Marcin, Szeleszczuk, Łukasz, Gurba, Agata, Lipiec, Szymon, Taciak, Przemysław, Szczepaniak, Remigiusz, Młynarczuk-Biały, Izabela, Fichna, Jakub
• Format: Article
• Language: English
• Subjects: Drug Safety and Pharmacovigilance; Medicine; Pharmacotherapy; Pharmacy
• ISSN: 1734-1140; 2299-5684; 2299-5684
• DOI: 10.1007/s43440-023-00558-1

Background Chronic inflammation in the course of inflammatory bowel disease may result in colon cancer, or colitis-associated colorectal cancer (CACRC). It is well established that CACRC is associated with oxidative stress and secretion of multiple pro-inflammatory cytokines, e.g. tumor necrosis factor-α. Recently, we proved that the administration of gold(III) complexes resulted in the alleviation of acute colitis in mice. The aim of the current study was to assess the antitumor effect of a novel series of gold(III) complexes: TGS 121, 404, 512, 701, 702, and 703. Materials Analyzed gold(III) complexes were screened in the in vitro studies using colorectal cancer and normal colon epithelium cell lines, SW480, HT-29, and CCD 841 CoN, and in vivo, in the CACRC mouse model. Results Of all tested complexes, TGS 121, 404, and 702 exhibited the strongest anti-tumor effect in in vitro viability assay of colon cancer cell lines and in in vivo CACRC model, in which these complexes decreased the total number of colonic tumors and macroscopic score. We also evidenced that the mechanism of action was linked to the enzymatic antioxidant system and inflammatory cytokines. Conclusions TGS 121, 404, and 702 present anti-tumor potential and are an attractive therapeutic option for colorectal cancer.