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In the clinical realm, platinum\u2010based drugs hold an important role in the chemotherapy of CRC. Nonetheless, a multitude of patients, due to tumor protein 53 (<jats:italic>TP53<\/jats:italic>) gene mutations, experience the emergence of drug resistance. This phenomenon gravely impairs the effectiveness of therapy and long\u2010term prognosis. Gallium, a metallic element akin to iron, has been reported that has the potential to be used to develop new metal anticancer drugs. In this study, we screened and established the gallium complex K6 as a potent antitumor agent in both in vitro and in vivo. K6 exhibited superior efficacy in impeding the growth, proliferation, and viability of CRC cells carrying <jats:italic>TP53<\/jats:italic> mutations compared to oxaliplatin. Mechanistically, K6 escalated reactive oxygen species levels and led deoxyribonucleic acid (DNA) damage. Furthermore, K6 effectively suppressed the phosphoinositide 3\u2010kinase (PI3K)\/protein kinase B (PKB)\/glycogen synthase kinase 3 beta (GSK3\u03b2) pathway, leading to the degradation of its downstream effectors myelocytomatosis (c\u2010Myc) and Krueppel\u2010like factor 5 (KLF5). Conversely, K6 diminished the protein expression of WW domain\u2010containing protein 1 (WWP1) while activating phosphatase and tensin homolog (PTEN) through c\u2010Myc degradation. This dual action further demonstrated the potential of K6 as a promising therapeutic compound for <jats:italic>TP53<\/jats:italic>\u2010mutated CRC.<\/jats:p>","DOI":"10.1002\/mco2.665","type":"journal-article","created":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T09:31:31Z","timestamp":1721813491000},"source":"Crossref","is-referenced-by-count":5,"title":["Gallium complex K6 inhibits colorectal cancer by increasing ROS levels to induce DNA damage and enhance phosphatase and tensin homolog activity"],"prefix":"10.1002","volume":"5","author":[{"given":"Wei","family":"Li","sequence":"first","affiliation":[{"name":"Yunnan Key Laboratory of Animal Models and Human Disease Mechanisms Kunming Institute of Zoology Chinese Academy of Sciences  Kunming China"},{"name":"Kunming College of Life Sciences University of Chinese Academy Sciences  Kunming 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