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Butylidenephthalide Abrogates the Snail-Induced Cancer Stemness in Oral Carcinomas
Oral cancer is one of the most common cancers worldwide, especially in South Central Asia. It has been suggested that cancer stem cells (CSC) play crucial roles in tumor relapse and metastasis, and approaches to target CSC may lead to promising results. Here, aldehyde dehydrogenase 1 (ALDH1) and CD4...
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/PMC9180956/ https://www.ncbi.nlm.nih.gov/pubmed/35682836 http://dx.doi.org/10.3390/ijms23116157 |
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author | Chen, Pei-Yin Chao, Shih-Chi Hsieh, Pei-Ling Liao, Yi-Wen Chu, Pei-Ming Harn, Horng-Jyh Yu, Cheng-Chia |
author_facet | Chen, Pei-Yin Chao, Shih-Chi Hsieh, Pei-Ling Liao, Yi-Wen Chu, Pei-Ming Harn, Horng-Jyh Yu, Cheng-Chia |
author_sort | Chen, Pei-Yin |
collection | PubMed |
description | Oral cancer is one of the most common cancers worldwide, especially in South Central Asia. It has been suggested that cancer stem cells (CSC) play crucial roles in tumor relapse and metastasis, and approaches to target CSC may lead to promising results. Here, aldehyde dehydrogenase 1 (ALDH1) and CD44 were utilized to isolate CSCs of oral cancer. Butylidenephthalide, a bioactive phthalide compound from Angelica sinensis, was tested for its anti-CSC effects. MTT assay showed that a lower concentration of butylidenephthalide was sufficient to inhibit the proliferation of patient-derived ALDH1(+)/CD44(+) cells without affecting normal cells. Administration of butylidenephthalide not only reduced ALDH1 activity and CD44 expression, it also suppressed the migration, invasion, and colony formation abilities of ALDH1(+)/CD44(+) cells using a transwell system and clonogenic assay. A patient-derived xenograft mouse model supported our in vitro findings that butylidenephthalide possessed the capacity to retard tumor development. We found that butylidenephthalide dose-dependently downregulated the gene and protein expression of Sox2 and Snail. Our results demonstrated that overexpression of Snail in ALDH1(-)/CD44(-) (non-CSCs) cells induced the CSC phenotypes, whereas butylidenephthalide treatment successfully diminished the enhanced self-renewal and propagating properties. In summary, this study showed that butylidenephthalide may serve as an adjunctive for oral cancer therapy. |
format | Online Article Text |
id | pubmed-9180956 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91809562022-06-10 Butylidenephthalide Abrogates the Snail-Induced Cancer Stemness in Oral Carcinomas Chen, Pei-Yin Chao, Shih-Chi Hsieh, Pei-Ling Liao, Yi-Wen Chu, Pei-Ming Harn, Horng-Jyh Yu, Cheng-Chia Int J Mol Sci Article Oral cancer is one of the most common cancers worldwide, especially in South Central Asia. It has been suggested that cancer stem cells (CSC) play crucial roles in tumor relapse and metastasis, and approaches to target CSC may lead to promising results. Here, aldehyde dehydrogenase 1 (ALDH1) and CD44 were utilized to isolate CSCs of oral cancer. Butylidenephthalide, a bioactive phthalide compound from Angelica sinensis, was tested for its anti-CSC effects. MTT assay showed that a lower concentration of butylidenephthalide was sufficient to inhibit the proliferation of patient-derived ALDH1(+)/CD44(+) cells without affecting normal cells. Administration of butylidenephthalide not only reduced ALDH1 activity and CD44 expression, it also suppressed the migration, invasion, and colony formation abilities of ALDH1(+)/CD44(+) cells using a transwell system and clonogenic assay. A patient-derived xenograft mouse model supported our in vitro findings that butylidenephthalide possessed the capacity to retard tumor development. We found that butylidenephthalide dose-dependently downregulated the gene and protein expression of Sox2 and Snail. Our results demonstrated that overexpression of Snail in ALDH1(-)/CD44(-) (non-CSCs) cells induced the CSC phenotypes, whereas butylidenephthalide treatment successfully diminished the enhanced self-renewal and propagating properties. In summary, this study showed that butylidenephthalide may serve as an adjunctive for oral cancer therapy. MDPI 2022-05-31 /pmc/articles/PMC9180956/ /pubmed/35682836 http://dx.doi.org/10.3390/ijms23116157 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 Chen, Pei-Yin Chao, Shih-Chi Hsieh, Pei-Ling Liao, Yi-Wen Chu, Pei-Ming Harn, Horng-Jyh Yu, Cheng-Chia Butylidenephthalide Abrogates the Snail-Induced Cancer Stemness in Oral Carcinomas |
title | Butylidenephthalide Abrogates the Snail-Induced Cancer Stemness in Oral Carcinomas |
title_full | Butylidenephthalide Abrogates the Snail-Induced Cancer Stemness in Oral Carcinomas |
title_fullStr | Butylidenephthalide Abrogates the Snail-Induced Cancer Stemness in Oral Carcinomas |
title_full_unstemmed | Butylidenephthalide Abrogates the Snail-Induced Cancer Stemness in Oral Carcinomas |
title_short | Butylidenephthalide Abrogates the Snail-Induced Cancer Stemness in Oral Carcinomas |
title_sort | butylidenephthalide abrogates the snail-induced cancer stemness in oral carcinomas |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9180956/ https://www.ncbi.nlm.nih.gov/pubmed/35682836 http://dx.doi.org/10.3390/ijms23116157 |
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