title: Dihydromyricetin promotes autophagy and apoptosis through ROS-STAT3 signaling in head and neck squamous cell carcinoma.
abstract: Chemotherapy is an effective weapon in the battle against cancer, but numerous cancer patients are either not sensitive to chemotherapy or develop drug resistance to current chemotherapy regimens. Therefore, an effective chemotherapy mechanism that enhances tumor sensitivity to chemotherapeutics is urgently needed. The aim of the present study was to determine the antitumor activity of dihydromyricetin (DHM) on head and neck squamous cell carcinoma (HNSCC) and its underlying mechanisms. We demonstrated that DHM can markedly induce apoptotic cell death and autophagy in HNSCC cells. Meanwhile, increased autophagy inhibited apoptosis. Pharmacological or genetic inhibition of autophagy further sensitized the HNSCC cells to DHM-induced apoptosis. Mechanistic analysis showed that the antitumor of DHM may be due to the activation phosphorylation of signal transducer and activator of transcription 3 (p-STAT3), which contributed to autophagy. Importantly, DHM triggered reactive oxygen species (ROS) generation in the HNSCC cells and the levels of ROS decreased with N-acetyl-cysteine (NAC), a ROS scavenger. Moreover, NAC abrogated the effects of DHM on STAT3-dependent autophagy. Overall, the following critical issues were observed: first, DHM increased the p-STAT3-dependent autophagy by generating ROS-signaling pathways in head and neck squamous cell carcinoma. Second, inhibiting autophagy could enhance DHM-induced apoptosis in head and neck squamous cell carcinoma.
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Teng-Fei
authors.initials: TF
authors.lastname: Fan
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Tian-Fu
authors.initials: TF
authors.lastname: Wu
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Bu
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Si-Rui
authors.initials: SR
authors.lastname: Ma
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Yi-Cun
authors.initials: YC
authors.lastname: Li
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Mao
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.|Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Sun
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.|Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors.forename: Wen-Feng
authors.initials: WF
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D044948:Flavonols / Q000494:pharmacology*; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D044948:Flavonols; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; C472036:dihydromyricetin
keywords: apoptosis; autophagy; dihydromyricetin; head and neck squamous cell carcinoma; reactive oxygen species