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Role of JNK activation in paclitaxel-induced apoptosis in human head and neck squamous cell carcinoma

It has been reported that paclitaxel activates cell cycle arrest and increases caspase protein expression to induce apoptosis in head and neck squamous cell carcinoma (HNSCC) cell lines. However, the potential signaling pathway regulating this apoptotic phenomenon remains unclear. The present study...

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Autores principales: Lan, Yu-Yan, Chen, Ying-Hui, Liu, Cheng, Tung, Kuo-Lung, Wu, Yen-Ting, Lin, Sheng-Chieh, Wu, Chin-Han, Chang, Hong-Yi, Chen, Yung-Chia, Huang, Bu-Miin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358625/
https://www.ncbi.nlm.nih.gov/pubmed/34457060
http://dx.doi.org/10.3892/ol.2021.12966
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author Lan, Yu-Yan
Chen, Ying-Hui
Liu, Cheng
Tung, Kuo-Lung
Wu, Yen-Ting
Lin, Sheng-Chieh
Wu, Chin-Han
Chang, Hong-Yi
Chen, Yung-Chia
Huang, Bu-Miin
author_facet Lan, Yu-Yan
Chen, Ying-Hui
Liu, Cheng
Tung, Kuo-Lung
Wu, Yen-Ting
Lin, Sheng-Chieh
Wu, Chin-Han
Chang, Hong-Yi
Chen, Yung-Chia
Huang, Bu-Miin
author_sort Lan, Yu-Yan
collection PubMed
description It has been reported that paclitaxel activates cell cycle arrest and increases caspase protein expression to induce apoptosis in head and neck squamous cell carcinoma (HNSCC) cell lines. However, the potential signaling pathway regulating this apoptotic phenomenon remains unclear. The present study used OEC-M1 cells to investigate the underlying molecular mechanism of paclitaxel-induced apoptosis. Following treatment with paclitaxel, cell viability was assessed via the MTT assay. Necrosis, apoptosis, cell cycle and mitochondrial membrane potential (∆Ψm) were analyzed via flow cytometric analyses, respectively. Western blot analysis was performed to detect the expression levels of proteins associated with the MAPK and caspase signaling pathways. The results demonstrated that low-dose paclitaxel (50 nM) induced apoptosis but not necrosis in HNSCC cells. In addition, paclitaxel activated the c-Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase or p38 mitogen-activated protein kinase. The paclitaxel-activated JNK contributed to paclitaxel-induced apoptosis, activation of caspase-3, −6, −7, −8 and −9, and reduction of ∆Ψm. In addition, caspase-8 and −9 inhibitors, respectively, significantly decreased paclitaxel-induced apoptosis. Notably, Bid was truncated following treatment with paclitaxel. Taken together, the results of the present study suggest that paclitaxel-activated JNK is required for caspase activation and loss of ∆Ψm, which results in apoptosis of HNSCC cells. These results may provide mechanistic basis for designing more effective paclitaxel-combining regimens to treat HNSCC.
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spelling pubmed-83586252021-08-26 Role of JNK activation in paclitaxel-induced apoptosis in human head and neck squamous cell carcinoma Lan, Yu-Yan Chen, Ying-Hui Liu, Cheng Tung, Kuo-Lung Wu, Yen-Ting Lin, Sheng-Chieh Wu, Chin-Han Chang, Hong-Yi Chen, Yung-Chia Huang, Bu-Miin Oncol Lett Articles It has been reported that paclitaxel activates cell cycle arrest and increases caspase protein expression to induce apoptosis in head and neck squamous cell carcinoma (HNSCC) cell lines. However, the potential signaling pathway regulating this apoptotic phenomenon remains unclear. The present study used OEC-M1 cells to investigate the underlying molecular mechanism of paclitaxel-induced apoptosis. Following treatment with paclitaxel, cell viability was assessed via the MTT assay. Necrosis, apoptosis, cell cycle and mitochondrial membrane potential (∆Ψm) were analyzed via flow cytometric analyses, respectively. Western blot analysis was performed to detect the expression levels of proteins associated with the MAPK and caspase signaling pathways. The results demonstrated that low-dose paclitaxel (50 nM) induced apoptosis but not necrosis in HNSCC cells. In addition, paclitaxel activated the c-Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase or p38 mitogen-activated protein kinase. The paclitaxel-activated JNK contributed to paclitaxel-induced apoptosis, activation of caspase-3, −6, −7, −8 and −9, and reduction of ∆Ψm. In addition, caspase-8 and −9 inhibitors, respectively, significantly decreased paclitaxel-induced apoptosis. Notably, Bid was truncated following treatment with paclitaxel. Taken together, the results of the present study suggest that paclitaxel-activated JNK is required for caspase activation and loss of ∆Ψm, which results in apoptosis of HNSCC cells. These results may provide mechanistic basis for designing more effective paclitaxel-combining regimens to treat HNSCC. D.A. Spandidos 2021-10 2021-08-03 /pmc/articles/PMC8358625/ /pubmed/34457060 http://dx.doi.org/10.3892/ol.2021.12966 Text en Copyright: © Lan et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Lan, Yu-Yan
Chen, Ying-Hui
Liu, Cheng
Tung, Kuo-Lung
Wu, Yen-Ting
Lin, Sheng-Chieh
Wu, Chin-Han
Chang, Hong-Yi
Chen, Yung-Chia
Huang, Bu-Miin
Role of JNK activation in paclitaxel-induced apoptosis in human head and neck squamous cell carcinoma
title Role of JNK activation in paclitaxel-induced apoptosis in human head and neck squamous cell carcinoma
title_full Role of JNK activation in paclitaxel-induced apoptosis in human head and neck squamous cell carcinoma
title_fullStr Role of JNK activation in paclitaxel-induced apoptosis in human head and neck squamous cell carcinoma
title_full_unstemmed Role of JNK activation in paclitaxel-induced apoptosis in human head and neck squamous cell carcinoma
title_short Role of JNK activation in paclitaxel-induced apoptosis in human head and neck squamous cell carcinoma
title_sort role of jnk activation in paclitaxel-induced apoptosis in human head and neck squamous cell carcinoma
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358625/
https://www.ncbi.nlm.nih.gov/pubmed/34457060
http://dx.doi.org/10.3892/ol.2021.12966
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