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Asiatic Acid, Extracted from Centella asiatica and Induces Apoptosis Pathway through the Phosphorylation p38 Mitogen-Activated Protein Kinase in Cisplatin-Resistant Nasopharyngeal Carcinoma Cells
Nasopharyngeal carcinoma (NPC) is an important issue in Asia because of its unique geographical and ethnic distribution. Cisplatin-based regimens are commonly the first-line used chemotherapy, but resistance and toxicities remain a problem. Therefore, the use of anticancer agents derived from natura...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072674/ https://www.ncbi.nlm.nih.gov/pubmed/31991751 http://dx.doi.org/10.3390/biom10020184 |
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author | Liu, Yen-Tze Chuang, Yi-Ching Lo, Yu-Sheng Lin, Chia-Chieh Hsi, Yi-Ting Hsieh, Ming-Ju Chen, Mu-Kuan |
author_facet | Liu, Yen-Tze Chuang, Yi-Ching Lo, Yu-Sheng Lin, Chia-Chieh Hsi, Yi-Ting Hsieh, Ming-Ju Chen, Mu-Kuan |
author_sort | Liu, Yen-Tze |
collection | PubMed |
description | Nasopharyngeal carcinoma (NPC) is an important issue in Asia because of its unique geographical and ethnic distribution. Cisplatin-based regimens are commonly the first-line used chemotherapy, but resistance and toxicities remain a problem. Therefore, the use of anticancer agents derived from natural products may be a solution. Asiatic acid (AA), extracted from Centella asiatica, was found to have anticancer activity in various cancers. The aim of this study is to examine the cytotoxic effect and mediated mechanism of AA in cisplatin-resistant NPC cells. The results shows that AA significantly reduce the cell viability of cisplatin-resistant NPC cell lines (cis NPC-039 and cis NPC-BM) in dose and time dependent manners caused by apoptosis through the both intrinsic and extrinsic apoptotic pathways, including altered mitochondrial membrane potential, activated death receptors, increased Bax expression, and upregulated caspase 3, 8, and 9. The Western blot analysis of AA-treated cell lines reveals that the phosphorylation of MAPK pathway proteins is involved. Further, the results of adding inhibitors of these proteins indicates that the phosphorylation of p38 are the key mediators in AA-induced apoptosis in cisplatin-resistant human NPC cells. This is the first study to demonstrate the AA-induced apoptotic pathway through the phosphorylation p38 in human cisplatin-resistant nasopharyngeal carcinoma. AA is expected to be another therapeutic option for cisplatin-resistant NPC because of the promising anti-cancer effect and fewer toxic properties. |
format | Online Article Text |
id | pubmed-7072674 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-70726742020-03-19 Asiatic Acid, Extracted from Centella asiatica and Induces Apoptosis Pathway through the Phosphorylation p38 Mitogen-Activated Protein Kinase in Cisplatin-Resistant Nasopharyngeal Carcinoma Cells Liu, Yen-Tze Chuang, Yi-Ching Lo, Yu-Sheng Lin, Chia-Chieh Hsi, Yi-Ting Hsieh, Ming-Ju Chen, Mu-Kuan Biomolecules Article Nasopharyngeal carcinoma (NPC) is an important issue in Asia because of its unique geographical and ethnic distribution. Cisplatin-based regimens are commonly the first-line used chemotherapy, but resistance and toxicities remain a problem. Therefore, the use of anticancer agents derived from natural products may be a solution. Asiatic acid (AA), extracted from Centella asiatica, was found to have anticancer activity in various cancers. The aim of this study is to examine the cytotoxic effect and mediated mechanism of AA in cisplatin-resistant NPC cells. The results shows that AA significantly reduce the cell viability of cisplatin-resistant NPC cell lines (cis NPC-039 and cis NPC-BM) in dose and time dependent manners caused by apoptosis through the both intrinsic and extrinsic apoptotic pathways, including altered mitochondrial membrane potential, activated death receptors, increased Bax expression, and upregulated caspase 3, 8, and 9. The Western blot analysis of AA-treated cell lines reveals that the phosphorylation of MAPK pathway proteins is involved. Further, the results of adding inhibitors of these proteins indicates that the phosphorylation of p38 are the key mediators in AA-induced apoptosis in cisplatin-resistant human NPC cells. This is the first study to demonstrate the AA-induced apoptotic pathway through the phosphorylation p38 in human cisplatin-resistant nasopharyngeal carcinoma. AA is expected to be another therapeutic option for cisplatin-resistant NPC because of the promising anti-cancer effect and fewer toxic properties. MDPI 2020-01-25 /pmc/articles/PMC7072674/ /pubmed/31991751 http://dx.doi.org/10.3390/biom10020184 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Liu, Yen-Tze Chuang, Yi-Ching Lo, Yu-Sheng Lin, Chia-Chieh Hsi, Yi-Ting Hsieh, Ming-Ju Chen, Mu-Kuan Asiatic Acid, Extracted from Centella asiatica and Induces Apoptosis Pathway through the Phosphorylation p38 Mitogen-Activated Protein Kinase in Cisplatin-Resistant Nasopharyngeal Carcinoma Cells |
title | Asiatic Acid, Extracted from Centella asiatica and Induces Apoptosis Pathway through the Phosphorylation p38 Mitogen-Activated Protein Kinase in Cisplatin-Resistant Nasopharyngeal Carcinoma Cells |
title_full | Asiatic Acid, Extracted from Centella asiatica and Induces Apoptosis Pathway through the Phosphorylation p38 Mitogen-Activated Protein Kinase in Cisplatin-Resistant Nasopharyngeal Carcinoma Cells |
title_fullStr | Asiatic Acid, Extracted from Centella asiatica and Induces Apoptosis Pathway through the Phosphorylation p38 Mitogen-Activated Protein Kinase in Cisplatin-Resistant Nasopharyngeal Carcinoma Cells |
title_full_unstemmed | Asiatic Acid, Extracted from Centella asiatica and Induces Apoptosis Pathway through the Phosphorylation p38 Mitogen-Activated Protein Kinase in Cisplatin-Resistant Nasopharyngeal Carcinoma Cells |
title_short | Asiatic Acid, Extracted from Centella asiatica and Induces Apoptosis Pathway through the Phosphorylation p38 Mitogen-Activated Protein Kinase in Cisplatin-Resistant Nasopharyngeal Carcinoma Cells |
title_sort | asiatic acid, extracted from centella asiatica and induces apoptosis pathway through the phosphorylation p38 mitogen-activated protein kinase in cisplatin-resistant nasopharyngeal carcinoma cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072674/ https://www.ncbi.nlm.nih.gov/pubmed/31991751 http://dx.doi.org/10.3390/biom10020184 |
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