Abstract
Due to the increasing incidence and high mortality associated with colorectal cancer (CRC), novel therapeutic strategies are urgently needed. Classic chemotherapy against CRC is based on oxaliplatin and other cisplatin analogues; however, platinum-based therapy lacks selectivity to cancer cells and leads to deleterious side effects. In addition, tumor resistance to oxaliplatin is related to chemotherapy failure. Gold(I) derivatives are a promising alternative to platinum complexes, since instead of interacting with DNA, they target proteins overexpressed on tumor cells, thus leading to less side effects than, but a comparable antitumor effect to, platinum derivatives. Moreover, given the huge potential of gold nanoparticles, the role of gold in CRC chemotherapy is not limited to gold(I) complexes. Gold nanoparticles have been found to be able to overcome multidrug resistance along with reduced side effects due to a more efficient uptake of classic drugs. Moreover, the use of gold nanoparticles has enhanced the effect of traditional therapies such as radiotherapy, photothermal therapy, or photodynamic therapy, and has displayed a potential role in diagnosis as a consequence of their optic properties. Herein, we have reviewed the most recent advances in the use of gold(I) derivatives and gold nanoparticles in CRC therapy.
Highlights
Colorectal cancer (CRC) is the third most common type of cancer and has become one of the leading causes of death from cancers worldwide
The corresponding luminescent complexes derived from coumarines functionalized by a propynyloxy group at the 4- or 7-position or two propynyloxy groups in the 6,7-positions have triggered strong cytotoxicity against HT-29 colon carcinoma (IC50 values of 1.84, 2.13, and 3.14 μM respectively), which was attributed to the cation tetraphenylphosphonium and their high inhibition of the enzyme thioredoxin reductase [122]
Due to the significant side effects of platinum-containing drugs, along with tumor resistance to treatment, new metal-based compounds have been developed and the data collected and exposed in this work suggest that gold could be a promising alternative in the future
Summary
Colorectal cancer (CRC) is the third most common type of cancer and has become one of the leading causes of death from cancers worldwide. Biscarbene gold(I) derivatives 70a–f with NHC ligands derived from the plant metabolite combretastatin (able to induce a rapid vascular shutdown in solid tumors) similar to the imidazole unit used in complexes 68a–d, have displayed a strong cytotoxicity against HT-29 (IC50 ranging from 0.06 to 0.16 μM) and HCT-116 (IC50 ranging from 0.07 to 0.30 μM) colon carcinoma cells, with the methoxy compounds 70a and 70d being the most active These complexes showed an anti-angiogenic effect on different in vitro and in vivo models, further assays on CRC animal models are needed to ensure their use in this kind of tumor [96].
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