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Proapoptotic Effect and Molecular Docking Analysis of Curcumin–Resveratrol Hybrids in Colorectal Cancer Chemoprevention

Different hybrids based on curcumin and resveratrol were previously synthesized and characterized by spectroscopic techniques. The most active molecules (3a, 3e, 3i, and 3k) were evaluated in vitro as an approach to determine the possible mechanism of action of the hybrids. The results indicated tha...

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Autores principales: Moreno-Q, Gustavo, Herrera-R, Angie, Yepes, Andres F., Naranjo, Tonny W., Cardona-G, Wilson
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9181936/
https://www.ncbi.nlm.nih.gov/pubmed/35684424
http://dx.doi.org/10.3390/molecules27113486
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author Moreno-Q, Gustavo
Herrera-R, Angie
Yepes, Andres F.
Naranjo, Tonny W.
Cardona-G, Wilson
author_facet Moreno-Q, Gustavo
Herrera-R, Angie
Yepes, Andres F.
Naranjo, Tonny W.
Cardona-G, Wilson
author_sort Moreno-Q, Gustavo
collection PubMed
description Different hybrids based on curcumin and resveratrol were previously synthesized and characterized by spectroscopic techniques. The most active molecules (3a, 3e, 3i, and 3k) were evaluated in vitro as an approach to determine the possible mechanism of action of the hybrids. The results indicated that the evaluated curcumin/resveratrol hybrids induce mitochondrial instability in SW620 and SW480 cells. Moreover, these molecules caused a loss in membrane integrity, suggesting an apoptotic process mediated by caspases after the treatment with compounds 3i (SW480) and 3k (SW620). In addition, the results suggest that the mechanism of action of the hybrids could be independent of the p53 status. Furthermore, hybrids 3e and 3i caused G0/G1 phase arrest, which highlights the potential of these molecules not only as cytotoxic but also as cytostatic compounds. Hybrids 3e and 3i caused a negative modulation of the matrix metalloproteinase 7 (MMP7) on SW480 cells. These curcumin resveratrol hybrids could be potential candidates for further investigations in the search for potential chemopreventive agents, even in those cases with resistance to conventional chemotherapy because of the lack of p53 expression or function. Molecular docking simulations showed that compounds 3e, 3i, and 3k bind efficiently to proapoptotic human caspases 3/7 proteins, as well as human MMP-7 and p53, which, in turn, could explain at the molecular level the in vitro cytotoxic effect of these compounds in SW480 and SW620 colon cancer cell lines.
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spelling pubmed-91819362022-06-10 Proapoptotic Effect and Molecular Docking Analysis of Curcumin–Resveratrol Hybrids in Colorectal Cancer Chemoprevention Moreno-Q, Gustavo Herrera-R, Angie Yepes, Andres F. Naranjo, Tonny W. Cardona-G, Wilson Molecules Article Different hybrids based on curcumin and resveratrol were previously synthesized and characterized by spectroscopic techniques. The most active molecules (3a, 3e, 3i, and 3k) were evaluated in vitro as an approach to determine the possible mechanism of action of the hybrids. The results indicated that the evaluated curcumin/resveratrol hybrids induce mitochondrial instability in SW620 and SW480 cells. Moreover, these molecules caused a loss in membrane integrity, suggesting an apoptotic process mediated by caspases after the treatment with compounds 3i (SW480) and 3k (SW620). In addition, the results suggest that the mechanism of action of the hybrids could be independent of the p53 status. Furthermore, hybrids 3e and 3i caused G0/G1 phase arrest, which highlights the potential of these molecules not only as cytotoxic but also as cytostatic compounds. Hybrids 3e and 3i caused a negative modulation of the matrix metalloproteinase 7 (MMP7) on SW480 cells. These curcumin resveratrol hybrids could be potential candidates for further investigations in the search for potential chemopreventive agents, even in those cases with resistance to conventional chemotherapy because of the lack of p53 expression or function. Molecular docking simulations showed that compounds 3e, 3i, and 3k bind efficiently to proapoptotic human caspases 3/7 proteins, as well as human MMP-7 and p53, which, in turn, could explain at the molecular level the in vitro cytotoxic effect of these compounds in SW480 and SW620 colon cancer cell lines. MDPI 2022-05-28 /pmc/articles/PMC9181936/ /pubmed/35684424 http://dx.doi.org/10.3390/molecules27113486 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
Moreno-Q, Gustavo
Herrera-R, Angie
Yepes, Andres F.
Naranjo, Tonny W.
Cardona-G, Wilson
Proapoptotic Effect and Molecular Docking Analysis of Curcumin–Resveratrol Hybrids in Colorectal Cancer Chemoprevention
title Proapoptotic Effect and Molecular Docking Analysis of Curcumin–Resveratrol Hybrids in Colorectal Cancer Chemoprevention
title_full Proapoptotic Effect and Molecular Docking Analysis of Curcumin–Resveratrol Hybrids in Colorectal Cancer Chemoprevention
title_fullStr Proapoptotic Effect and Molecular Docking Analysis of Curcumin–Resveratrol Hybrids in Colorectal Cancer Chemoprevention
title_full_unstemmed Proapoptotic Effect and Molecular Docking Analysis of Curcumin–Resveratrol Hybrids in Colorectal Cancer Chemoprevention
title_short Proapoptotic Effect and Molecular Docking Analysis of Curcumin–Resveratrol Hybrids in Colorectal Cancer Chemoprevention
title_sort proapoptotic effect and molecular docking analysis of curcumin–resveratrol hybrids in colorectal cancer chemoprevention
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9181936/
https://www.ncbi.nlm.nih.gov/pubmed/35684424
http://dx.doi.org/10.3390/molecules27113486
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