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

doi:10.3892/ol.2021.12966

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

Authors:
- Yu-Yan Lan
- Ying-Hui Chen
- Cheng Liu
- Kuo-Lung Tung
- Yen-Ting Wu
- Sheng-Chieh Lin
- Chin-Han Wu
- Hong-Yi Chang
- Yung-Chia Chen
- Bu-Miin Huang
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Affiliations: Department of Physical Therapy, Shu‑Zen Junior College of Medicine and Management, Kaohsiung 82144, Taiwan, R.O.C., Department of Anesthesia, Chi‑Mei Medical Center, Liouying, Tainan 73657, Taiwan, R.O.C., Department of Optometry, Shu‑Zen Junior College of Medicine and Management, Kaohsiung 82144, Taiwan, R.O.C., Department of Pathology, Golden Hospital, Pingtung 90049, Taiwan, R.O.C., Department of Biotechnology and Food Technology, College of Engineering, Southern Taiwan University of Science and Technology, Tainan 71005, Taiwan, R.O.C., Department of Anatomy, School of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan, R.O.C., Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan, R.O.C.
Published online on: August 3, 2021 https://doi.org/10.3892/ol.2021.12966
Article Number: 705
Copyright: © Lan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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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