Mulberry Leaf Polyphenol Extract and Rutin Induces Autophagy Regulated by p53 in Human Hepatoma HepG2 Cells

doi:10.3390/ph14121310

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/23774

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/23774

Title:	Mulberry Leaf Polyphenol Extract and Rutin Induces Autophagy Regulated by p53 in Human Hepatoma HepG2 Cells
Authors:	Yu, MH;Tsai, MC;Wang, CC;Wu, SW;Chang, YJ;Wu, CH;Wang, CJ
Keywords:	mulberry leaf polyphenol extract;rutin;human hepatoma HepG2 cells;autophagy;p53
Date:	2021
Issue Date:	2022-08-05T09:42:39Z (UTC)
Publisher:	MDPI
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-alpha (PFT-alpha) inhibited autophagy and increased apoptotic response in MLPE-treated HepG2 cells. PFT-alpha treatment also reversed MLPE-induced PI3K, p-AKT, and FASN suppression. Thus, co-treatment with MLPE and PFT-alpha 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.
URI:	http://dx.doi.org/10.3390/ph14121310 https://www.webofscience.com/wos/woscc/full-record/WOS:000736892900001 https://ir.csmu.edu.tw:8080/handle/310902500/23774
Relation:	PHARMACEUTICALS ,2021,v14,issue 12
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

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