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Dihydromyricetin induces autophagy in HepG2 cells involved in inhibition of mTOR and regulating its upstream pathways.
Food Chem Toxicol. 2014 Apr; 66:7-13.FC

Abstract

Dihydromyricetin (DHM), a bioactive flavonoid compound extracted from the stems and leaves of Ampelopsis grossedentata, has oxidation resistance, anti-tumor and free radical scavenging capabilities. In this study, we found that DHM-induced autophagy inhibited the cell proliferation in HepG2 cells. The transmission electron microscopy results showed that DHM induced significantly autophagosome characteristics like autophagolysosome containing degraded cellular content. GFP labled LC3 plasma transfection showed that LC3 largely diffused to punctate structures with DHM treatment, while lysosomal-rich/acidic compartments detected using LysoTracker Red staining. In addition, DHM promoted the expressions of LC3-II and Beclin-1 in a dose- and time-dependent manner. Further study showed that DHM suppressed the activation of mTOR (mammalian targets of rapamycin) involved in regulating its upstream signaling pathways including extracellular signal-regulated kinase 1/2 (ERK1/2), AMPK (AMP-activated kinase) and class III phosphatidylinositol 3-kinase/phosphoinositide-dependent protein kinase 1/protein kinase B (PI3K/PDK 1/Akt) pathways. Taken together, all the results demonstrated that DHM-induced autophagy inhibited the cell proliferation in HepG2 cells, the possible mechanism involved in inhibition of mTOR activation and regulating the related upstream signaling pathways.

Authors+Show Affiliations

Laboratory of Regenerative Medicine, Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200433, China.Laboratory of Regenerative Medicine, Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.Key Laboratory of Age-associated Cardiac-cerebral Vascular Disease of Guangdong Province, Institute of Neurology, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.Key Laboratory of Age-associated Cardiac-cerebral Vascular Disease of Guangdong Province, Institute of Neurology, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.Laboratory of Regenerative Medicine, Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.Laboratory of Regenerative Medicine, Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.Laboratory of Regenerative Medicine, Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.Laboratory of Regenerative Medicine, Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.Laboratory of Regenerative Medicine, Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China. Electronic address: hepatolab@163.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24444546

Citation

Xia, Juan, et al. "Dihydromyricetin Induces Autophagy in HepG2 Cells Involved in Inhibition of mTOR and Regulating Its Upstream Pathways." Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association, vol. 66, 2014, pp. 7-13.
Xia J, Guo S, Fang T, et al. Dihydromyricetin induces autophagy in HepG2 cells involved in inhibition of mTOR and regulating its upstream pathways. Food Chem Toxicol. 2014;66:7-13.
Xia, J., Guo, S., Fang, T., Feng, D., Zhang, X., Zhang, Q., Liu, J., Liu, B., Li, M., & Zhu, R. (2014). Dihydromyricetin induces autophagy in HepG2 cells involved in inhibition of mTOR and regulating its upstream pathways. Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association, 66, 7-13. https://doi.org/10.1016/j.fct.2014.01.014
Xia J, et al. Dihydromyricetin Induces Autophagy in HepG2 Cells Involved in Inhibition of mTOR and Regulating Its Upstream Pathways. Food Chem Toxicol. 2014;66:7-13. PubMed PMID: 24444546.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dihydromyricetin induces autophagy in HepG2 cells involved in inhibition of mTOR and regulating its upstream pathways. AU - Xia,Juan, AU - Guo,Shiwei, AU - Fang,Tao, AU - Feng,Du, AU - Zhang,Xingli, AU - Zhang,Qingyu, AU - Liu,Jie, AU - Liu,Bin, AU - Li,Mingyi, AU - Zhu,Runzhi, Y1 - 2014/01/18/ PY - 2013/10/12/received PY - 2014/01/06/revised PY - 2014/01/09/accepted PY - 2014/1/22/entrez PY - 2014/1/22/pubmed PY - 2015/2/6/medline KW - Autophagy KW - DHM KW - Tumor KW - mTOR SP - 7 EP - 13 JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association JO - Food Chem. Toxicol. VL - 66 N2 - Dihydromyricetin (DHM), a bioactive flavonoid compound extracted from the stems and leaves of Ampelopsis grossedentata, has oxidation resistance, anti-tumor and free radical scavenging capabilities. In this study, we found that DHM-induced autophagy inhibited the cell proliferation in HepG2 cells. The transmission electron microscopy results showed that DHM induced significantly autophagosome characteristics like autophagolysosome containing degraded cellular content. GFP labled LC3 plasma transfection showed that LC3 largely diffused to punctate structures with DHM treatment, while lysosomal-rich/acidic compartments detected using LysoTracker Red staining. In addition, DHM promoted the expressions of LC3-II and Beclin-1 in a dose- and time-dependent manner. Further study showed that DHM suppressed the activation of mTOR (mammalian targets of rapamycin) involved in regulating its upstream signaling pathways including extracellular signal-regulated kinase 1/2 (ERK1/2), AMPK (AMP-activated kinase) and class III phosphatidylinositol 3-kinase/phosphoinositide-dependent protein kinase 1/protein kinase B (PI3K/PDK 1/Akt) pathways. Taken together, all the results demonstrated that DHM-induced autophagy inhibited the cell proliferation in HepG2 cells, the possible mechanism involved in inhibition of mTOR activation and regulating the related upstream signaling pathways. SN - 1873-6351 UR - https://www.unboundmedicine.com/medline/citation/24444546/Dihydromyricetin_induces_autophagy_in_HepG2_cells_involved_in_inhibition_of_mTOR_and_regulating_its_upstream_pathways_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0278-6915(14)00028-3 DB - PRIME DP - Unbound Medicine ER -