A novel ECG analog 4-(S)-(2,4,6-trimethylthiobenzyl)-epigallocatechin gallate selectively induces apoptosis of B16-F10 melanoma via activation of autophagy and ROS

作者：Xie, Jing; Yun, Ju-ping; Yang, Ya-nan; Hua, Fang; Zhang, Xiao-wei; Lin, Heng; Lv, Xiao-xi; Li, Ke; Zhang, Pei-cheng^*; Hu, Zhuo-wei^*

来源：Scientific Reports, 2017, 7(1): 42194.

DOI：10.1038/srep42194

• GREEN TEA POLYPHENOL
• CELL-DEATH
• CANCER-CELLS
• FLOW-CYTOMETRY
• IN-VIVO
• EGCG
• MECHANISMS
• STRESS
• AMPK
• (-)-EPIGALLOCATECHIN-3-GALLATE

Autophagy-induced cancer cell death has become a novel strategy for the development of cancer therapeutic drugs. Numerous studies have indicated that green tea polyphenols induce both autophagy and apoptosis in a variety of cancer cells. Here, we synthesized a series of green tea polyphenol analogues, among which JP8 was shown to potently activate autophagy. JP8 treatment had a stronger effect on apoptosis in B16-F10 melanoma cells than that in normal AML-12 hepatocytes. JP8 selectively resulted in reactive oxygen species (ROS) accumulation in B16-F10 cells, and this effect was associated with corresponding increases in key components of the ER stress-mediated apoptosis pathway. Pharmacological inhibition of ROS by N-acetyl-L-cysteine (NAC) attenuated JP8-induced autophagy and apoptosis, indicating an upstream role of ROS in JP8-induced autophagy. An in vivo study showed that JP8 had significant antitumor effects in a B16-F10 xenograft mouse model. Our results indicate that JP8 is a novel anticancer candidate with both autophagy and ROS induction activities.

• 出版日期2017-2-10
• 单位河北医科大学; 中国医学科学院北京协和医院; 北京协和医学院; 中日友好医院; 天然药物活性物质与功能国家重点实验室