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Dihydromyricetin promotes autophagy and apoptosis through ROS-STAT3 signaling in head and neck squamous cell carcinoma.
Oncotarget. 2016 Sep 13; 7(37):59691-59703.O

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+Show Affiliations

The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.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.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.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27474168

Citation

Fan, Teng-Fei, et al. "Dihydromyricetin Promotes Autophagy and Apoptosis Through ROS-STAT3 Signaling in Head and Neck Squamous Cell Carcinoma." Oncotarget, vol. 7, no. 37, 2016, pp. 59691-59703.
Fan TF, Wu TF, Bu LL, et al. Dihydromyricetin promotes autophagy and apoptosis through ROS-STAT3 signaling in head and neck squamous cell carcinoma. Oncotarget. 2016;7(37):59691-59703.
Fan, T. F., Wu, T. F., Bu, L. L., Ma, S. R., Li, Y. C., Mao, L., Sun, Z. J., & Zhang, W. F. (2016). Dihydromyricetin promotes autophagy and apoptosis through ROS-STAT3 signaling in head and neck squamous cell carcinoma. Oncotarget, 7(37), 59691-59703. https://doi.org/10.18632/oncotarget.10836
Fan TF, et al. Dihydromyricetin Promotes Autophagy and Apoptosis Through ROS-STAT3 Signaling in Head and Neck Squamous Cell Carcinoma. Oncotarget. 2016 Sep 13;7(37):59691-59703. PubMed PMID: 27474168.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dihydromyricetin promotes autophagy and apoptosis through ROS-STAT3 signaling in head and neck squamous cell carcinoma. AU - Fan,Teng-Fei, AU - Wu,Tian-Fu, AU - Bu,Lin-Lin, AU - Ma,Si-Rui, AU - Li,Yi-Cun, AU - Mao,Liang, AU - Sun,Zhi-Jun, AU - Zhang,Wen-Feng, PY - 2016/04/15/received PY - 2016/07/10/accepted PY - 2016/7/31/pubmed PY - 2018/2/7/medline PY - 2016/7/31/entrez KW - apoptosis KW - autophagy KW - dihydromyricetin KW - head and neck squamous cell carcinoma KW - reactive oxygen species SP - 59691 EP - 59703 JF - Oncotarget JO - Oncotarget VL - 7 IS - 37 N2 - 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. SN - 1949-2553 UR - https://www.unboundmedicine.com/medline/citation/27474168/Dihydromyricetin_promotes_autophagy_and_apoptosis_through_ROS_STAT3_signaling_in_head_and_neck_squamous_cell_carcinoma_ L2 - http://www.impactjournals.com/oncotarget/misc/linkedout.php?pii=10836 DB - PRIME DP - Unbound Medicine ER -