Neferine promotes the apoptosis of HNSCC through the accumulation of p62/SQSTM1 caused by autophagic flux inhibition
| Title: | Neferine promotes the apoptosis of HNSCC through the accumulation of p62/SQSTM1 caused by autophagic flux inhibition |
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| Authors: | Junjian Jiang, Yue He, Xiaoguang Li, Xiao Tang, Fengshuo Zhu, Chunyue Ma, Zhonglong Liu, Yu Han, Yinuo Li |
| Source: | International Journal of Molecular Medicine |
| Publisher Information: | D.A. Spandidos, 2021. |
| Publication Year: | 2021 |
| Subject Terms: | 0301 basic medicine, Male, autophagy, Cell Survival, MAP Kinase Signaling System, Cell, Nelumbo, head and neck squamous cell carcinoma, Benzylisoquinolines, 03 medical and health sciences, Mice, 0302 clinical medicine, Cell Line, Tumor, Sequestosome-1 Protein, Genetics, medicine, Animals, Humans, ASK1, chemistry.chemical_classification, Reactive oxygen species, Mice, Inbred BALB C, Oncogene, Squamous Cell Carcinoma of Head and Neck, Autophagy, apoptosis, Autophagosomes, General Medicine, Articles, Cell cycle, medicine.disease, Head and neck squamous-cell carcinoma, stomatognathic diseases, 030104 developmental biology, medicine.anatomical_structure, chemistry, Apoptosis, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Seeds, Cancer research, neferine, Reactive Oxygen Species, Drugs, Chinese Herbal |
| Description: | Head and neck squamous cell carcinoma (HNSCC), one of the most common malignancies worldwide, often has a poor prognosis due to the associated metastasis and chemoresistance. Hence, the development of more effective chemotherapeutics is critical. Neferine, a bisbenzylisoquinoline alkaloid isolated from the seed embryo of Nelumbo nucifera (common name: Lotus), exerts antitumor effects by regulating apoptosis and autophagy pathways, making it a potential therapeutic option for HNSCC. In our study, it was revealed that neferine inhibited the growth and induced the apoptosis of HNSCC cells both in vitro and in vivo. Furthermore, the results revealed that neferine activated the ASK1/JNK pathway by increasing reactive oxygen species production, resulting in the subsequent induction of apoptosis and the regulation of canonical autophagy in HNSCC cells. Moreover, a novel pro‑apoptotic mechanism was described for neferine via the activation of caspase‑8 following the accumulation of p62, which was caused by autophagic flux inhibition. These findings provided insights into the mechanisms responsible for the anticancer effect of neferine, specifically highlighting the crosstalk that occured between apoptosis and autophagy, which was mediated by p62 in HNSCC. Hence, the neferine‑induced inhibition of autophagic flux may serve as the basis for a potential adjuvant therapy for HNSCC. |
| Language: | English |
| ISSN: | 1791-244X 1107-3756 |
| Access URL: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6e0484e5529431c35906d362d7e0bb8a http://europepmc.org/articles/PMC8128420 |
| Rights: | OPEN |
| Accession Number: | edsair.doi.dedup.....6e0484e5529431c35906d362d7e0bb8a |
| Database: | OpenAIRE |
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| ISSN: | 1791244X 11073756 |
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