Open AccessNeferine promotes the apoptosis of HNSCC through the accumulation of p62/SQSTM1 caused by autophagic flux inhibition
Author(s) -
Fengshuo Zhu,
Xiaoguang Li,
X. Tang,
Junjian Jiang,
Yu Han,
Yinuo Li,
Chunyue Ma,
Zhonglong Liu,
Yue He
Publication year - 2021
Publication title -
international journal of molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.048
H-Index - 90
eISSN - 1791-244X
pISSN - 1107-3756
DOI - 10.3892/ijmm.2021.4957
Subject(s) - autophagy , apoptosis , cancer research , head and neck squamous cell carcinoma , biology , microbiology and biotechnology , cell cycle , chemistry , cancer , biochemistry , genetics , head and neck cancer
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.