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Microsatellite Status and IκBα Expression Levels Predict Sensitivity to Pharmaceutical Curcumin in Colorectal Cancer Cells
SIMPLE SUMMARY: The global burden of colorectal cancer is high. Chemotherapy has been the backbone of colorectal cancer therapy for decades. Toxic side effects and frequently occurring drug resistances remain challenging problems. Therefore, exploring natural compounds with low or even no toxicity h...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8870219/ https://www.ncbi.nlm.nih.gov/pubmed/35205780 http://dx.doi.org/10.3390/cancers14041032 |
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author | Lu, Lili Przybylla, Randy Shang, Yuru Dai, Meng Krohn, Mathias Krämer, Oliver Holger Mullins, Christina Susanne Linnebacher, Michael |
author_facet | Lu, Lili Przybylla, Randy Shang, Yuru Dai, Meng Krohn, Mathias Krämer, Oliver Holger Mullins, Christina Susanne Linnebacher, Michael |
author_sort | Lu, Lili |
collection | PubMed |
description | SIMPLE SUMMARY: The global burden of colorectal cancer is high. Chemotherapy has been the backbone of colorectal cancer therapy for decades. Toxic side effects and frequently occurring drug resistances remain challenging problems. Therefore, exploring natural compounds with low or even no toxicity holds great potential. However, natural curcumin is poorly absorbed, limiting its clinical use. Therefore, our focus was to screen different molecular types of colorectal cancer to find the ones with the highest sensitivity to curcumin. We observed very individual responses to curcumin for various colorectal cancer cell lines. Most curcumin-sensitive cell lines were of the microsatellite-stable molecular type, and expressed high baseline levels of the IκBα protein. Contrarily, curcumin-resistant lines were mainly microsatellite instable, with low baseline IκBα levels. Considering all of the data obtained, we conclude that patients with microsatellite-stable tumors and high baseline IκBα protein expression would benefit from treatment with novel curcumin formulations and derivatives. ABSTRACT: Clinical utilization of curcumin in colorectal cancer (CRC) was revived as a result of the development of novel curcumin formulations with improved bioavailability. Additionally, identification of biomarkers for curcumin sensitivity would also promote successful clinical applications. Here, we wanted to identify such biomarkers in order to establish a predictive model for curcumin sensitivity. Thirty-two low-passage CRC cell lines with specified tumor characteristics were included. Curcumin suppressed cell proliferation, yet sensitivity levels were distinct. Most curcumin-sensitive CRC cell lines were microsatellite stable and expressed high levels of IκBα. The predictive capacity of this biomarker combination possessed a statistical significance of 72% probability to distinguish correctly between curcumin-sensitive and -resistant CRC cell lines. Detailed functional analyses were performed with three sensitive and three resistant CRC cell lines. As curcumin’s mode of action, inhibition of NF-κB p65 activation via IκBα was identified. In consequence, we hypothesize that novel curcumin formulations—either alone or, more likely, in combination with standard therapeutics—can be expected to prove clinically beneficial for CRC patients with high IκBα expression levels. |
format | Online Article Text |
id | pubmed-8870219 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-88702192022-02-25 Microsatellite Status and IκBα Expression Levels Predict Sensitivity to Pharmaceutical Curcumin in Colorectal Cancer Cells Lu, Lili Przybylla, Randy Shang, Yuru Dai, Meng Krohn, Mathias Krämer, Oliver Holger Mullins, Christina Susanne Linnebacher, Michael Cancers (Basel) Article SIMPLE SUMMARY: The global burden of colorectal cancer is high. Chemotherapy has been the backbone of colorectal cancer therapy for decades. Toxic side effects and frequently occurring drug resistances remain challenging problems. Therefore, exploring natural compounds with low or even no toxicity holds great potential. However, natural curcumin is poorly absorbed, limiting its clinical use. Therefore, our focus was to screen different molecular types of colorectal cancer to find the ones with the highest sensitivity to curcumin. We observed very individual responses to curcumin for various colorectal cancer cell lines. Most curcumin-sensitive cell lines were of the microsatellite-stable molecular type, and expressed high baseline levels of the IκBα protein. Contrarily, curcumin-resistant lines were mainly microsatellite instable, with low baseline IκBα levels. Considering all of the data obtained, we conclude that patients with microsatellite-stable tumors and high baseline IκBα protein expression would benefit from treatment with novel curcumin formulations and derivatives. ABSTRACT: Clinical utilization of curcumin in colorectal cancer (CRC) was revived as a result of the development of novel curcumin formulations with improved bioavailability. Additionally, identification of biomarkers for curcumin sensitivity would also promote successful clinical applications. Here, we wanted to identify such biomarkers in order to establish a predictive model for curcumin sensitivity. Thirty-two low-passage CRC cell lines with specified tumor characteristics were included. Curcumin suppressed cell proliferation, yet sensitivity levels were distinct. Most curcumin-sensitive CRC cell lines were microsatellite stable and expressed high levels of IκBα. The predictive capacity of this biomarker combination possessed a statistical significance of 72% probability to distinguish correctly between curcumin-sensitive and -resistant CRC cell lines. Detailed functional analyses were performed with three sensitive and three resistant CRC cell lines. As curcumin’s mode of action, inhibition of NF-κB p65 activation via IκBα was identified. In consequence, we hypothesize that novel curcumin formulations—either alone or, more likely, in combination with standard therapeutics—can be expected to prove clinically beneficial for CRC patients with high IκBα expression levels. MDPI 2022-02-17 /pmc/articles/PMC8870219/ /pubmed/35205780 http://dx.doi.org/10.3390/cancers14041032 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 Lu, Lili Przybylla, Randy Shang, Yuru Dai, Meng Krohn, Mathias Krämer, Oliver Holger Mullins, Christina Susanne Linnebacher, Michael Microsatellite Status and IκBα Expression Levels Predict Sensitivity to Pharmaceutical Curcumin in Colorectal Cancer Cells |
title | Microsatellite Status and IκBα Expression Levels Predict Sensitivity to Pharmaceutical Curcumin in Colorectal Cancer Cells |
title_full | Microsatellite Status and IκBα Expression Levels Predict Sensitivity to Pharmaceutical Curcumin in Colorectal Cancer Cells |
title_fullStr | Microsatellite Status and IκBα Expression Levels Predict Sensitivity to Pharmaceutical Curcumin in Colorectal Cancer Cells |
title_full_unstemmed | Microsatellite Status and IκBα Expression Levels Predict Sensitivity to Pharmaceutical Curcumin in Colorectal Cancer Cells |
title_short | Microsatellite Status and IκBα Expression Levels Predict Sensitivity to Pharmaceutical Curcumin in Colorectal Cancer Cells |
title_sort | microsatellite status and iκbα expression levels predict sensitivity to pharmaceutical curcumin in colorectal cancer cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8870219/ https://www.ncbi.nlm.nih.gov/pubmed/35205780 http://dx.doi.org/10.3390/cancers14041032 |
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