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Ruthenium(II)–Cyclopentadienyl-Derived Complexes as New Emerging Anti-Colorectal Cancer Drugs

Colorectal cancer (CRC) is one of the most common malignancies and one of the leading causes of cancer-related death worldwide, urging the need for new and more efficient therapeutic approaches. Ruthenium complexes have emerged as attractive alternatives to traditional platinum-based compounds in th...

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Autores principales: Teixeira-Guedes, Catarina, Brás, Ana Rita, Teixeira, Ricardo G., Valente, Andreia, Preto, Ana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9228117/
https://www.ncbi.nlm.nih.gov/pubmed/35745864
http://dx.doi.org/10.3390/pharmaceutics14061293
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author Teixeira-Guedes, Catarina
Brás, Ana Rita
Teixeira, Ricardo G.
Valente, Andreia
Preto, Ana
author_facet Teixeira-Guedes, Catarina
Brás, Ana Rita
Teixeira, Ricardo G.
Valente, Andreia
Preto, Ana
author_sort Teixeira-Guedes, Catarina
collection PubMed
description Colorectal cancer (CRC) is one of the most common malignancies and one of the leading causes of cancer-related death worldwide, urging the need for new and more efficient therapeutic approaches. Ruthenium complexes have emerged as attractive alternatives to traditional platinum-based compounds in the treatment of CRC. This work aims to evaluate anti-CRC properties, as well as to identify the mechanisms of action of ruthenium complexes with the general formula [Ru(η(5)-C(5)H(4)R)(PPh(3))(4,4′-R′-2,2′-bipyridine)][CF(3)SO(3)], where R = CH(3), CHO or CH(2)OH and R′ = H, CH(3), CH(2)OH, or dibiotin ester. The complexes (Ru 1–7) displayed high bioactivity, as shown by low IC(50) concentrations against CRC cells, namely, RKO and SW480. Four of the most promising ruthenium complexes (Ru 2, 5–7) were phenotypically characterized and were shown to inhibit cell viability by decreasing cell proliferation, inducing cell cycle arrest, and increasing apoptosis. These findings were in accordance with the inhibition of MEK/ERK and PI3K/AKT signaling pathways. Ruthenium complexes also led to a decrease in cellular clonogenic ability and cell migration, which was associated with the disruption of F-actin cytoskeleton integrity. Here, we demonstrated that ruthenium complexes, especially Ru7, have a high anticancer effect against CRC cells and are promising drugs to be used as a new therapeutical strategy for CRC treatment.
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spelling pubmed-92281172022-06-25 Ruthenium(II)–Cyclopentadienyl-Derived Complexes as New Emerging Anti-Colorectal Cancer Drugs Teixeira-Guedes, Catarina Brás, Ana Rita Teixeira, Ricardo G. Valente, Andreia Preto, Ana Pharmaceutics Article Colorectal cancer (CRC) is one of the most common malignancies and one of the leading causes of cancer-related death worldwide, urging the need for new and more efficient therapeutic approaches. Ruthenium complexes have emerged as attractive alternatives to traditional platinum-based compounds in the treatment of CRC. This work aims to evaluate anti-CRC properties, as well as to identify the mechanisms of action of ruthenium complexes with the general formula [Ru(η(5)-C(5)H(4)R)(PPh(3))(4,4′-R′-2,2′-bipyridine)][CF(3)SO(3)], where R = CH(3), CHO or CH(2)OH and R′ = H, CH(3), CH(2)OH, or dibiotin ester. The complexes (Ru 1–7) displayed high bioactivity, as shown by low IC(50) concentrations against CRC cells, namely, RKO and SW480. Four of the most promising ruthenium complexes (Ru 2, 5–7) were phenotypically characterized and were shown to inhibit cell viability by decreasing cell proliferation, inducing cell cycle arrest, and increasing apoptosis. These findings were in accordance with the inhibition of MEK/ERK and PI3K/AKT signaling pathways. Ruthenium complexes also led to a decrease in cellular clonogenic ability and cell migration, which was associated with the disruption of F-actin cytoskeleton integrity. Here, we demonstrated that ruthenium complexes, especially Ru7, have a high anticancer effect against CRC cells and are promising drugs to be used as a new therapeutical strategy for CRC treatment. MDPI 2022-06-17 /pmc/articles/PMC9228117/ /pubmed/35745864 http://dx.doi.org/10.3390/pharmaceutics14061293 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Teixeira-Guedes, Catarina
Brás, Ana Rita
Teixeira, Ricardo G.
Valente, Andreia
Preto, Ana
Ruthenium(II)–Cyclopentadienyl-Derived Complexes as New Emerging Anti-Colorectal Cancer Drugs
title Ruthenium(II)–Cyclopentadienyl-Derived Complexes as New Emerging Anti-Colorectal Cancer Drugs
title_full Ruthenium(II)–Cyclopentadienyl-Derived Complexes as New Emerging Anti-Colorectal Cancer Drugs
title_fullStr Ruthenium(II)–Cyclopentadienyl-Derived Complexes as New Emerging Anti-Colorectal Cancer Drugs
title_full_unstemmed Ruthenium(II)–Cyclopentadienyl-Derived Complexes as New Emerging Anti-Colorectal Cancer Drugs
title_short Ruthenium(II)–Cyclopentadienyl-Derived Complexes as New Emerging Anti-Colorectal Cancer Drugs
title_sort ruthenium(ii)–cyclopentadienyl-derived complexes as new emerging anti-colorectal cancer drugs
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9228117/
https://www.ncbi.nlm.nih.gov/pubmed/35745864
http://dx.doi.org/10.3390/pharmaceutics14061293
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