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Licochalcone A Promotes the Ubiquitination of c-Met to Abrogate Gefitinib Resistance
Met proto-oncogene (MET) amplification and tyrosine-protein kinase Met (c-Met) overexpression confer gefitinib resistance in non-small cell lung cancer (NSCLC). The natural product Licochalcone A (Lico A) exhibits a broad range of inhibitory effects against various tumors. However, the effects of Li...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8930240/ https://www.ncbi.nlm.nih.gov/pubmed/35309168 http://dx.doi.org/10.1155/2022/5687832 |
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author | Han, Shuangze Li, Xiaoying Gan, Yu Li, Wei |
author_facet | Han, Shuangze Li, Xiaoying Gan, Yu Li, Wei |
author_sort | Han, Shuangze |
collection | PubMed |
description | Met proto-oncogene (MET) amplification and tyrosine-protein kinase Met (c-Met) overexpression confer gefitinib resistance in non-small cell lung cancer (NSCLC). The natural product Licochalcone A (Lico A) exhibits a broad range of inhibitory effects against various tumors. However, the effects of Lico A on c-Met signaling and gefitinib resistance in NSCLC remain unclear. In the present study, Lico A efficiently overcame gefitinib-acquired resistance in NSCLC cells by suppressing c-Met signaling. Lico A decreased cell viability and colony formation dose-dependently and impaired in vivo tumorigenesis of gefitinib-resistant HCC827 and PC-9 cells. Furthermore, Lico A induced intrinsic apoptosis and upregulated the protein expression levels of cleaved poly (ADP-ribose) polymerase and cleaved caspase 3. Lico A promoted the interaction between c-Met and E3 ligase c-Casitas B-lineage lymphoma (Cbl), which enhanced c-Cbl-mediated c-Met ubiquitination and degradation. Depletion of c-Cbl compromised Lico A-induced c-Met ubiquitination and its inhibitory efficacy in gefitinib-resistant NSCLC cells. Taken together, the results suggest that Lico A is a promising antitumor agent that might be used to overcome c-Met overexpression-mediated gefitinib resistance in NSCLC cells. |
format | Online Article Text |
id | pubmed-8930240 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-89302402022-03-18 Licochalcone A Promotes the Ubiquitination of c-Met to Abrogate Gefitinib Resistance Han, Shuangze Li, Xiaoying Gan, Yu Li, Wei Biomed Res Int Research Article Met proto-oncogene (MET) amplification and tyrosine-protein kinase Met (c-Met) overexpression confer gefitinib resistance in non-small cell lung cancer (NSCLC). The natural product Licochalcone A (Lico A) exhibits a broad range of inhibitory effects against various tumors. However, the effects of Lico A on c-Met signaling and gefitinib resistance in NSCLC remain unclear. In the present study, Lico A efficiently overcame gefitinib-acquired resistance in NSCLC cells by suppressing c-Met signaling. Lico A decreased cell viability and colony formation dose-dependently and impaired in vivo tumorigenesis of gefitinib-resistant HCC827 and PC-9 cells. Furthermore, Lico A induced intrinsic apoptosis and upregulated the protein expression levels of cleaved poly (ADP-ribose) polymerase and cleaved caspase 3. Lico A promoted the interaction between c-Met and E3 ligase c-Casitas B-lineage lymphoma (Cbl), which enhanced c-Cbl-mediated c-Met ubiquitination and degradation. Depletion of c-Cbl compromised Lico A-induced c-Met ubiquitination and its inhibitory efficacy in gefitinib-resistant NSCLC cells. Taken together, the results suggest that Lico A is a promising antitumor agent that might be used to overcome c-Met overexpression-mediated gefitinib resistance in NSCLC cells. Hindawi 2022-03-10 /pmc/articles/PMC8930240/ /pubmed/35309168 http://dx.doi.org/10.1155/2022/5687832 Text en Copyright © 2022 Shuangze Han et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Han, Shuangze Li, Xiaoying Gan, Yu Li, Wei Licochalcone A Promotes the Ubiquitination of c-Met to Abrogate Gefitinib Resistance |
title | Licochalcone A Promotes the Ubiquitination of c-Met to Abrogate Gefitinib Resistance |
title_full | Licochalcone A Promotes the Ubiquitination of c-Met to Abrogate Gefitinib Resistance |
title_fullStr | Licochalcone A Promotes the Ubiquitination of c-Met to Abrogate Gefitinib Resistance |
title_full_unstemmed | Licochalcone A Promotes the Ubiquitination of c-Met to Abrogate Gefitinib Resistance |
title_short | Licochalcone A Promotes the Ubiquitination of c-Met to Abrogate Gefitinib Resistance |
title_sort | licochalcone a promotes the ubiquitination of c-met to abrogate gefitinib resistance |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8930240/ https://www.ncbi.nlm.nih.gov/pubmed/35309168 http://dx.doi.org/10.1155/2022/5687832 |
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