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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

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单位: [1]State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, People’s Republic of China. [2]Department of Pharmacy, China-Japan Friendship Hospital, Beijing 100050, People’s Republic of China. [3]Laboratory of Antiviral Research, Institute of Medicinal Biotechnology.Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, People’s Republic of China.
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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.

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出版当年[2016]版:
大类 | 2 区 综合性期刊
小类 | 2 区 综合性期刊
最新[2025]版:
大类 | 3 区 综合性期刊
小类 | 3 区 综合性期刊
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出版当年[2015]版:
Q1 MULTIDISCIPLINARY SCIENCES
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Q1 MULTIDISCIPLINARY SCIENCES

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第一作者单位: [1]State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, People’s Republic of China. [2]Department of Pharmacy, China-Japan Friendship Hospital, Beijing 100050, People’s Republic of China.
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