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Growth Suppression in Lung Cancer Cells Harboring EGFR-C797S Mutation by Quercetin

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are approved treatments for non-small-cell lung cancer (NSCLC) patients harboring activating EGFR mutations. The EGFR C797S mutation is one of the known acquired-resistance mutations to the latest third-generation TKIs. At pre...

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Autores principales: Huang, Kuo-Yen, Wang, Tong-Hong, Chen, Chin-Chuan, Leu, Yann-Lii, Li, Hsin-Jung, Jhong, Cai-Ling, Chen, Chi-Yuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470952/
https://www.ncbi.nlm.nih.gov/pubmed/34572484
http://dx.doi.org/10.3390/biom11091271
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author Huang, Kuo-Yen
Wang, Tong-Hong
Chen, Chin-Chuan
Leu, Yann-Lii
Li, Hsin-Jung
Jhong, Cai-Ling
Chen, Chi-Yuan
author_facet Huang, Kuo-Yen
Wang, Tong-Hong
Chen, Chin-Chuan
Leu, Yann-Lii
Li, Hsin-Jung
Jhong, Cai-Ling
Chen, Chi-Yuan
author_sort Huang, Kuo-Yen
collection PubMed
description Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are approved treatments for non-small-cell lung cancer (NSCLC) patients harboring activating EGFR mutations. The EGFR C797S mutation is one of the known acquired-resistance mutations to the latest third-generation TKIs. At present, there are no clear options for treating patients who acquire resistance to third-generation TKIs. The acquisition of the EGFR C797S mutation was shown to upregulate the expression of AXL, a receptor tyrosine kinase of the TAM (TYRO3-AXL-MER) family, and the suppression of AXL is effective in reducing the growth of NSCLC cells harboring EGFR C797S. As quercetin was recently shown to inhibit AXL, quercetin may be effective in treating NSCLC cells harboring the EGFR C797S mutation. In this work, the cytotoxic effects of quercetin and its ability to inhibit tumor growth were examined in TKI-resistant NSCLC cells harboring the EGFR C797S mutation. We demonstrated that quercetin exhibited potent cytotoxic effects on NSCLC cells harboring the EGFR C797S mutation by inhibiting AXL and inducing apoptosis. Quercetin inhibited the tumor growth of xenografted NSCLC cells harboring the EGFR C797S mutation and appeared to act synergistically with brigatinib to inhibit of tumor growth in vivo. In summary, herein, we revealed that quercetin is an effective inhibitor for the treatment of non-small-cell lung cancer harboring the EGFR C797S mutation.
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spelling pubmed-84709522021-09-27 Growth Suppression in Lung Cancer Cells Harboring EGFR-C797S Mutation by Quercetin Huang, Kuo-Yen Wang, Tong-Hong Chen, Chin-Chuan Leu, Yann-Lii Li, Hsin-Jung Jhong, Cai-Ling Chen, Chi-Yuan Biomolecules Article Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are approved treatments for non-small-cell lung cancer (NSCLC) patients harboring activating EGFR mutations. The EGFR C797S mutation is one of the known acquired-resistance mutations to the latest third-generation TKIs. At present, there are no clear options for treating patients who acquire resistance to third-generation TKIs. The acquisition of the EGFR C797S mutation was shown to upregulate the expression of AXL, a receptor tyrosine kinase of the TAM (TYRO3-AXL-MER) family, and the suppression of AXL is effective in reducing the growth of NSCLC cells harboring EGFR C797S. As quercetin was recently shown to inhibit AXL, quercetin may be effective in treating NSCLC cells harboring the EGFR C797S mutation. In this work, the cytotoxic effects of quercetin and its ability to inhibit tumor growth were examined in TKI-resistant NSCLC cells harboring the EGFR C797S mutation. We demonstrated that quercetin exhibited potent cytotoxic effects on NSCLC cells harboring the EGFR C797S mutation by inhibiting AXL and inducing apoptosis. Quercetin inhibited the tumor growth of xenografted NSCLC cells harboring the EGFR C797S mutation and appeared to act synergistically with brigatinib to inhibit of tumor growth in vivo. In summary, herein, we revealed that quercetin is an effective inhibitor for the treatment of non-small-cell lung cancer harboring the EGFR C797S mutation. MDPI 2021-08-25 /pmc/articles/PMC8470952/ /pubmed/34572484 http://dx.doi.org/10.3390/biom11091271 Text en © 2021 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
Huang, Kuo-Yen
Wang, Tong-Hong
Chen, Chin-Chuan
Leu, Yann-Lii
Li, Hsin-Jung
Jhong, Cai-Ling
Chen, Chi-Yuan
Growth Suppression in Lung Cancer Cells Harboring EGFR-C797S Mutation by Quercetin
title Growth Suppression in Lung Cancer Cells Harboring EGFR-C797S Mutation by Quercetin
title_full Growth Suppression in Lung Cancer Cells Harboring EGFR-C797S Mutation by Quercetin
title_fullStr Growth Suppression in Lung Cancer Cells Harboring EGFR-C797S Mutation by Quercetin
title_full_unstemmed Growth Suppression in Lung Cancer Cells Harboring EGFR-C797S Mutation by Quercetin
title_short Growth Suppression in Lung Cancer Cells Harboring EGFR-C797S Mutation by Quercetin
title_sort growth suppression in lung cancer cells harboring egfr-c797s mutation by quercetin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470952/
https://www.ncbi.nlm.nih.gov/pubmed/34572484
http://dx.doi.org/10.3390/biom11091271
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