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Updated: Sep 3, 2025

Study of Protein-protein Interactions in Autophagy Research
Published on: September 9, 2017
Phloretin enhances autophagy by impairing AKT activation and inducing JNK-Beclin-1 pathway activation
Chenghe Fan1, Yilin Zhang1, Yu Tian1
1Department of Neurology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Erqi District, Zhengzhou 450052, China.
Abstract:
Phloretin is a type of dihydrochalcone that is primarily found in apples and has been reported to possess various potent biological activities, such as anticancer, antioxidant and anti-inflammatory effects. Our previous study has shown that phloretin induces apoptosis in human glioblastoma. In this study, we found that phloretin induced autophagy in SH-SY5Y cells by decreasing p-AKT and p-mTOR levels in the AKT/mTOR pathway and increasing the activation of JNK, the phosphorylation of c-Jun and the expression of Beclin-1. Moreover, the upregulation of Beclin-1 was decreased by SP600125 or a siRNA against c-Jun. Furthermore, SP600125 and siRNAs against c-Jun and Beclin-1 inhibited phloretin-induced autophagy. In addition, inhibition of phloretin-induced autophagy by cotreatment with phloretin and 3-MA decreased phloretin-induced cytotoxicity to SH-SY5Y cells. In conclusion, our results suggest that the AKT/mTOR pathway and JNK-mediated Beclin-1 expression are involved in phloretin-induced autophagy. Phloretin can be used to protect neurons during phloretin treatment of glioblastoma.
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