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© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

The edible leaves of the mulberry (Morus alba L.) plant are used worldwide. They contain abundant polyphenolic compounds with strong anticancer properties. We previously revealed that apoptosis was mediated in p53-negative Hep3B cells, and mulberry leaf polyphenol extract (MLPE) induced autophagy in p53-transfected Hep3B cells. However, how this autophagy is induced by p53 in human hepatoma HepG2 (p53 wild type) cells remains unclear. In the current study, MLPE induced autophagy, as demonstrated by enhanced acidic vesicular organelle staining, by upregulating beclin-1, increasing LC3-II conversion, and phosphorylating AMPK. In HepG2 cells, these processes were associated with p53. Western blot also revealed phosphatidylinositol-3 kinase (PI3K), p-AKT, and fatty acid synthase (FASN) suppression in MLPE-treated cells. Moreover, treatment with the p53 inhibitor pifithrin-α (PFT-α) inhibited autophagy and increased apoptotic response in MLPE-treated HepG2 cells. PFT-α treatment also reversed MLPE-induced PI3K, p-AKT, and FASN suppression. Thus, co-treatment with MLPE and PFT-α significantly increased caspase-3, caspase-8, and cytochrome c release, indicating that p53 deficiency caused the apoptosis. In addition, rutin, a bioactive polyphenol in MLPE, may affect autophagy in HepG2 cells. This study demonstrates that MLPE is a potential anticancer agent targeting autophagy and apoptosis in cells with p53 status. Moreover, this work provides insight into the mechanism of p53 action in MLPE-induced cytotoxicity in hepatocellular carcinoma.

Details

Title
Mulberry Leaf Polyphenol Extract and Rutin Induces Autophagy Regulated by p53 in Human Hepatoma HepG2 Cells
Author
Meng-Hsun Yu 1   VIAFID ORCID Logo  ; Ming-Chang, Tsai 2 ; Wang, Chi-Chih 2   VIAFID ORCID Logo  ; Sheng-Wen, Wu 3 ; Ya-Ju, Chang 4 ; Cheng-Hsun Wu 5 ; Chau-Jong, Wang 6 

 Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan; [email protected] (M.-H.Y.); [email protected] (M.-C.T.); [email protected] (C.-C.W.); [email protected] (Y.-J.C.); Department of Health Industry Technology Management, Chung Shan Medical University, Taichung 402, Taiwan 
 Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan; [email protected] (M.-H.Y.); [email protected] (M.-C.T.); [email protected] (C.-C.W.); [email protected] (Y.-J.C.); School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan; [email protected]; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung 402, Taiwan 
 School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan; [email protected]; Division of Nephrology, Department of Medicine, Chung Shan Medical University Hospital, Taichung 402, Taiwan 
 Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan; [email protected] (M.-H.Y.); [email protected] (M.-C.T.); [email protected] (C.-C.W.); [email protected] (Y.-J.C.) 
 Department of Anatomy, China Medical University, Taichung 406, Taiwan; Department of Biochemistry, China Medical University, Taichung 406, Taiwan 
 Department of Health Industry Technology Management, Chung Shan Medical University, Taichung 402, Taiwan; Department of Medical Research, Chung Shan Medical University Hospital, Taichung 402, Taiwan 
First page
1310
Publication year
2021
Publication date
2021
Publisher
MDPI AG
e-ISSN
14248247
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2612813596
Copyright
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.