Gold (III) Derivatives in Colon Cancer Treatment

Abstract

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.

Bioactivity and Development of Small Non-Platinum Metal-Based Chemotherapeutics

“…In fact, the most relevant biological effect proposed for Au(III) derivatives is still the inhibition of TrxR. Alterative mechanisms have been also proposed over the years to support cellular-specific antiproliferative effects, i.e., the inhibition of topoisomerase, targeting of mitochondrial functions, apoptosis induction, proteasome inhibition, and modulation of specific kinases [ 78 , 254 , 255 ]. It is noteworthy that recent studies focusing on innate and adaptive antitumour immunity have explored the effects of a possible reversal in cancer cell immune escape by both Au(I) (including auranofin) and Au(III)-based agents via a direct action on immune cell functions, leading to an overall improved anticancer activity.…”

Synthesis, characterization, antitumor potential, and investigation of mechanism of action of copper(ii) complexes with acylpyruvates as ligands: interactions with biomolecules and kinetic study

“…[11][12][13][14][15] One of the most important is the replacement of platinum metal ions with some other metal that shows less toxicity or, in an even better case, with some essential metal. [16][17][18] Keeping in mind the previous and knowing that copper is an essential element with numerous biological functions in the human organism, as well as our previous experiences with copper compounds, we came up with the idea to examine the antitumor potential of a series of copper(II) complexes. A small series of new copper(II) complexes with biologically signicant ligands such as acylpyruvate (Fig.…”

Downregulation of hsa-miR-135b-5p Inhibits Cell Proliferation, Migration, and Invasion in Colon Adenocarcinoma

“…Colon cancer is the most common malignant tumor in the gastrointestinal tract and ranks third and second in terms of morbidity and mortality, respectively, among all solid cancers [1][2][3]. Approximately 80-90% of colon cancers are colon adenocarcinomas (COADs) based on pathologic classification [4,5].…”