Neferine promotes the apoptosis of HNSCC through the accumulation of p62/SQSTM1 caused by autophagic flux inhibition

Zhu,Fengshuo; Li,Xiaoguang; Tang,Xiao; Jiang,Junjian; Han,Yu; Li,Yinuo; Ma,Chunyue; Liu,Zhonglong; He,Yue

doi:10.3892/ijmm.2021.4957

Neferine promotes the apoptosis of HNSCC through the accumulation of p62/SQSTM1 caused by autophagic flux inhibition

Authors:
- Fengshuo Zhu
- Xiaoguang Li
- Xiao Tang
- Junjian Jiang
- Yu Han
- Yinuo Li
- Chunyue Ma
- Zhonglong Liu
- Yue He
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Affiliations: Department of Oral Maxillofacial‑Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Disease, Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai 200011, P.R. China, Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Published online on: May 10, 2021 https://doi.org/10.3892/ijmm.2021.4957
Article Number: 124
Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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