Dihydromyricetin induces autophagy in HepG2 cells involved in inhibition of mTOR and regulating its upstream pathways.
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.
Laboratory of Regenerative Medicine, Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
Juan
J
Xia
Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200433, China.
Shiwei
S
Guo
Laboratory of Regenerative Medicine, Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
Tao
T
Fang
Key Laboratory of Age-associated Cardiac-cerebral Vascular Disease of Guangdong Province, Institute of Neurology, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
Du
D
Feng
Key Laboratory of Age-associated Cardiac-cerebral Vascular Disease of Guangdong Province, Institute of Neurology, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
Xingli
X
Zhang
Laboratory of Regenerative Medicine, Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
Qingyu
Q
Zhang
Laboratory of Regenerative Medicine, Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
Jie
J
Liu
Laboratory of Regenerative Medicine, Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
Bin
B
Liu
Laboratory of Regenerative Medicine, Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
Mingyi
M
Li
Laboratory of Regenerative Medicine, Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China. Electronic address: hepatolab@163.com.
Runzhi
R
Zhu
D001343:Autophagy / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D044948:Flavonols / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D046529:Microscopy, Electron, Transmission; D010766:Phosphorylation; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D044948:Flavonols; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; C472036:dihydromyricetin
Autophagy; DHM; Tumor; mTOR