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The Phenolic compound Kaempferol overcomes 5-fluorouracil resistance in human resistant LS174 colon cancer cells
Resistance to 5-Fluorouracil chemotherapy is a major cause of therapeutic failure in colon cancer cure. Development of combined therapies constitutes an effective strategy to inhibit cancer cells and prevent the emergence of drug resistance. For this purpose, we investigated the anti-tumoral effect...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6336835/ https://www.ncbi.nlm.nih.gov/pubmed/30655588 http://dx.doi.org/10.1038/s41598-018-36808-z |
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author | Riahi-Chebbi, Ichrak Souid, Soumaya Othman, Houcemeddine Haoues, Meriam Karoui, Habib Morel, Alain Srairi-Abid, Najet Essafi, Makram Essafi-Benkhadir, Khadija |
author_facet | Riahi-Chebbi, Ichrak Souid, Soumaya Othman, Houcemeddine Haoues, Meriam Karoui, Habib Morel, Alain Srairi-Abid, Najet Essafi, Makram Essafi-Benkhadir, Khadija |
author_sort | Riahi-Chebbi, Ichrak |
collection | PubMed |
description | Resistance to 5-Fluorouracil chemotherapy is a major cause of therapeutic failure in colon cancer cure. Development of combined therapies constitutes an effective strategy to inhibit cancer cells and prevent the emergence of drug resistance. For this purpose, we investigated the anti-tumoral effect of thirteen phenolic compounds, from the Tunisian quince Cydonia oblonga Miller, alone or combined to 5-FU, on the human 5-FU-resistant LS174-R colon cancer cells in comparison to parental cells. Our results showed that only Kaempferol was able to chemo-sensitize 5-FU-resistant LS174-R cells. This phenolic compound combined with 5-FU exerted synergistic inhibitory effect on cell viability. This combination enhanced the apoptosis and induced cell cycle arrest of both chemo-resistant and sensitive cells through impacting the expression levels of different cellular effectors. Kaempferol also blocked the production of reactive oxygen species (ROS) and modulated the expression of JAK/STAT3, MAPK, PI3K/AKT and NF-κB. In silico docking analysis suggested that the potent anti-tumoral effect of Kaempferol, compared to its two analogs (Kaempferol 3-O-glucoside and Kampferol 3-O-rutinoside), can be explained by the absence of glucosyl groups. Overall, our data propose Kaempferol as a potential chemotherapeutic agent to be used alone or in combination with 5-FU to overcome colon cancer drug resistance. |
format | Online Article Text |
id | pubmed-6336835 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-63368352019-01-22 The Phenolic compound Kaempferol overcomes 5-fluorouracil resistance in human resistant LS174 colon cancer cells Riahi-Chebbi, Ichrak Souid, Soumaya Othman, Houcemeddine Haoues, Meriam Karoui, Habib Morel, Alain Srairi-Abid, Najet Essafi, Makram Essafi-Benkhadir, Khadija Sci Rep Article Resistance to 5-Fluorouracil chemotherapy is a major cause of therapeutic failure in colon cancer cure. Development of combined therapies constitutes an effective strategy to inhibit cancer cells and prevent the emergence of drug resistance. For this purpose, we investigated the anti-tumoral effect of thirteen phenolic compounds, from the Tunisian quince Cydonia oblonga Miller, alone or combined to 5-FU, on the human 5-FU-resistant LS174-R colon cancer cells in comparison to parental cells. Our results showed that only Kaempferol was able to chemo-sensitize 5-FU-resistant LS174-R cells. This phenolic compound combined with 5-FU exerted synergistic inhibitory effect on cell viability. This combination enhanced the apoptosis and induced cell cycle arrest of both chemo-resistant and sensitive cells through impacting the expression levels of different cellular effectors. Kaempferol also blocked the production of reactive oxygen species (ROS) and modulated the expression of JAK/STAT3, MAPK, PI3K/AKT and NF-κB. In silico docking analysis suggested that the potent anti-tumoral effect of Kaempferol, compared to its two analogs (Kaempferol 3-O-glucoside and Kampferol 3-O-rutinoside), can be explained by the absence of glucosyl groups. Overall, our data propose Kaempferol as a potential chemotherapeutic agent to be used alone or in combination with 5-FU to overcome colon cancer drug resistance. Nature Publishing Group UK 2019-01-17 /pmc/articles/PMC6336835/ /pubmed/30655588 http://dx.doi.org/10.1038/s41598-018-36808-z Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Riahi-Chebbi, Ichrak Souid, Soumaya Othman, Houcemeddine Haoues, Meriam Karoui, Habib Morel, Alain Srairi-Abid, Najet Essafi, Makram Essafi-Benkhadir, Khadija The Phenolic compound Kaempferol overcomes 5-fluorouracil resistance in human resistant LS174 colon cancer cells |
title | The Phenolic compound Kaempferol overcomes 5-fluorouracil resistance in human resistant LS174 colon cancer cells |
title_full | The Phenolic compound Kaempferol overcomes 5-fluorouracil resistance in human resistant LS174 colon cancer cells |
title_fullStr | The Phenolic compound Kaempferol overcomes 5-fluorouracil resistance in human resistant LS174 colon cancer cells |
title_full_unstemmed | The Phenolic compound Kaempferol overcomes 5-fluorouracil resistance in human resistant LS174 colon cancer cells |
title_short | The Phenolic compound Kaempferol overcomes 5-fluorouracil resistance in human resistant LS174 colon cancer cells |
title_sort | phenolic compound kaempferol overcomes 5-fluorouracil resistance in human resistant ls174 colon cancer cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6336835/ https://www.ncbi.nlm.nih.gov/pubmed/30655588 http://dx.doi.org/10.1038/s41598-018-36808-z |
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