Gold (III) Derivatives in Colon Cancer Treatment

Cancer is one of the leading causes of morbidity and mortality worldwide. Colorectal cancer (CRC) is the third most frequently diagnosed cancer in men and the second in women. Standard patterns of antitumor therapy, including cisplatin, are ineffective due to their lack of specificity for tumor cells, development of drug resistance, and severe side effects. For this reason, new methods and strategies for CRC treatment are urgently needed. Current research includes novel platinum (Pt)- and other metal-based drugs such as gold (Au), silver (Ag), iridium (Ir), or ruthenium (Ru). Au(III) compounds are promising drug candidates for CRC treatment due to their structural similarity to Pt(II). Their advantage is their relatively good solubility in water, but their disadvantage is an unsatisfactory stability under physiological conditions. Due to these limitations, work is still underway to improve the formula of Au(III) complexes by combining with various types of ligands capable of stabilizing the Au(III) cation and preventing its reduction under physiological conditions. This review summarizes the achievements in the field of stable Au(III) complexes with potential cytotoxic activity restricted to cancer cells. Moreover, it has been shown that not nucleic acids but various protein structures such as thioredoxin reductase (TrxR) mediate the antitumor effects of Au derivatives. The state of the art of the in vivo studies so far conducted is also described.

Automated summary

Cancer is a major cause of illness and death worldwide. Colorectal cancer is the third most common cancer in men and the second most common in women. Standard antitumor therapies, such as cisplatin, have limitations due to their lack of specificity for tumor cells, drug resistance development, and severe side effects. Therefore, new methods and strategies for treating colorectal cancer are urgently needed. Current research focuses on novel platinum and other metal-based drugs, such as gold, silver, iridium, or ruthenium. Au(III) compounds are considered promising candidates for colorectal cancer treatment due to their structural similarity to Pt(II). However, their stability under physiological conditions needs improvement by combining with various ligands. This review summarizes the progress in developing stable Au(III) complexes with potential cytotoxic activity against cancer cells. Additionally, it highlights that the anticancer effects of Au derivatives are mediated by protein structures, such as thioredoxin reductase, rather than nucleic acids. The current state of in vivo studies is also discussed.