Dihydromyricetin induces autophagy in HepG2 cells involved in inhibition of mTOR and regulating its upstream pathways

作者：Xia, Juan; Guo, Shiwei; Fang, Tao; Feng, Du; Zhang, Xingli; Zhang, Qingyu; Liu, Jie; Liu, Bin; Li, Mingyi^*; Zhu, Runzhi

来源：Food and Chemical Toxicology, 2014, 66: 7-13.

DOI：10.1016/j.fct.2014.01.014

• DHM
• Tumor
• Autophagy
• mTOR

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 OHM induced significantly autophagosome characteristics like autophagolysosome containing degraded cellular content. GFP labled LC3 plasma transfection showed that LC3 largely diffused to punctate structures with OHM 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 OHM-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.

• 出版日期2014-4
• 单位广东医科大学; 中国人民解放军第二军医大学