TY - JOUR AB - 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. AD - 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 AU - Zhu,Fengshuo AU - Li,Xiaoguang AU - Tang,Xiao AU - Jiang,Junjian AU - Han,Yu AU - Li,Yinuo AU - Ma,Chunyue AU - Liu,Zhonglong AU - He,Yue DA - 2021/07/01 DO - 10.3892/ijmm.2021.4957 IS - 1 JO - Int J Mol Med KW - neferine apoptosis autophagy head and neck squamous cell carcinoma PY - 2021 SN - 1107-3756 1791-244X SP - 124 ST - Neferine promotes the apoptosis of HNSCC through the accumulation of p62/SQSTM1 caused by autophagic flux inhibition T2 - International Journal of Molecular Medicine TI - Neferine promotes the apoptosis of HNSCC through the accumulation of p62/SQSTM1 caused by autophagic flux inhibition UR - https://doi.org/10.3892/ijmm.2021.4957 VL - 48 ER -