Abstract
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.
Highlights
Autophagy is a catabolic process in which cells respond to external stresses by recycling intracellular components, including proteins, ribosomes, lipids, and even entire organelles
The results revealed that the major contents of Rhodiola crenulata and Rhodiola kirilowii were ECG polymers (ECGp) and EGCG polymers (EGCGp), respectively
The R. crenulata and R. kirilowii root extracts were further purified by a macroporous adsorption resin (HP-20) column to yield ECGp and EGCGp, respectively
Summary
Autophagy is a catabolic process in which cells respond to external stresses by recycling intracellular components, including proteins, ribosomes, lipids, and even entire organelles. Green tea has been the subject of numerous studies due to its beneficial effects on multiple diseases, including cancer, atherosclerosis, and cardiovascular diseases[10,11,12,13,14]. These healing properties are attributable to its abundant polyphenolic catechins, such as epigallocatechin-3-gallate (ECG) and epigallocatechin gallate (EGCG)[15,16]. We aimed to identify novel polyphenol analogs with potent autophagy-inducing and tumor inhibition activities. In vivo antitumor activity was examined, and the results showed that JP8 is a promising therapeutic candidate with both autophagy- and ROS-modulating activities
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