Bioactive components and mechanisms of poplar propolis in inhibiting proliferation of human hepatocellular carcinoma HepG2 cells

Background: The aim of this study was to elucidate the bioactive components and anti-tumor mechanism of poplar propolis extract obtained from North China (CP) in human hepatocellular carcinoma HepG2 cells in vitro. Methods: Cell viability and proliferation were measured by SRB assay and EdU prolifer...

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Autores principales:	Hui Liu, Junya Li, Wenwen Yuan, Shengyu Hao, Meng Wang, Fei Wang, Hongzhuan Xuan
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Poplar propolis Hepatocellular carcinoma Apoptosis Hippo/YAP pathway PI3K/AKT pathway Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/542a94f37c57478686c02fbda349d13b
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spelling	oai:doaj.org-article:542a94f37c57478686c02fbda349d13b2021-11-14T04:30:22ZBioactive components and mechanisms of poplar propolis in inhibiting proliferation of human hepatocellular carcinoma HepG2 cells0753-332210.1016/j.biopha.2021.112364https://doaj.org/article/542a94f37c57478686c02fbda349d13b2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0753332221011483https://doaj.org/toc/0753-3322Background: The aim of this study was to elucidate the bioactive components and anti-tumor mechanism of poplar propolis extract obtained from North China (CP) in human hepatocellular carcinoma HepG2 cells in vitro. Methods: Cell viability and proliferation were measured by SRB assay and EdU proliferation test kit, respectively. Cell migration was evaluated by scratching test. Reactive oxygen species (ROS) production and mitochondrial membrane potential were investigated with the fluorescent probes, DCHF and JC-1, respectively. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were inspected by measurement kits. Apoptosis was assessed by acridine orange (AO) and Hoechst 33258 staining. Levels of Bax, Bcl-2, caspase 9, caspase 3, PARP, MMP-2, MMP-9, PI3K/p-PI3K, AKT/p-AKT, p38MAPK/p-p38 MAPK, ERK/p-ERK, LATS2, YAP, TAZ and TEAD1 were assessed by western blotting, respectively. Results: The bioactive components of CP inhibiting HepG2 cells were mainly flavonoids, and esters. CP induced HepG2 apoptosis through a mitochondrial-dependent intrinsic pathway with elevated the levels of cleaved PARP, cleaved caspase 3, and Bax and decreased the expressions of Bcl-2 and procaspase 9. It seemed that CP triggered apoptosis by activation of the p38 MAPK and inactivation of p-ERK. More importantly, we found that CP suppressed the Hippo pathway, leading to inactivation of YAP/TAZ and TEAD1 and inhibition of PI3K/AKT signaling molecules. Conclusion: CP exerted excellent anti-proliferation and pro-apoptosis actions in HepG2 cells by inactivation of the loop between the Hippo/YAP and PI3K/AKT pathways, and may be a promising therapy for HCC.Hui LiuJunya LiWenwen YuanShengyu HaoMeng WangFei WangHongzhuan XuanElsevierarticlePoplar propolisHepatocellular carcinomaApoptosisHippo/YAP pathwayPI3K/AKT pathwayTherapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 144, Iss , Pp 112364- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Poplar propolis Hepatocellular carcinoma Apoptosis Hippo/YAP pathway PI3K/AKT pathway Therapeutics. Pharmacology RM1-950
spellingShingle	Poplar propolis Hepatocellular carcinoma Apoptosis Hippo/YAP pathway PI3K/AKT pathway Therapeutics. Pharmacology RM1-950 Hui Liu Junya Li Wenwen Yuan Shengyu Hao Meng Wang Fei Wang Hongzhuan Xuan Bioactive components and mechanisms of poplar propolis in inhibiting proliferation of human hepatocellular carcinoma HepG2 cells
description	Background: The aim of this study was to elucidate the bioactive components and anti-tumor mechanism of poplar propolis extract obtained from North China (CP) in human hepatocellular carcinoma HepG2 cells in vitro. Methods: Cell viability and proliferation were measured by SRB assay and EdU proliferation test kit, respectively. Cell migration was evaluated by scratching test. Reactive oxygen species (ROS) production and mitochondrial membrane potential were investigated with the fluorescent probes, DCHF and JC-1, respectively. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were inspected by measurement kits. Apoptosis was assessed by acridine orange (AO) and Hoechst 33258 staining. Levels of Bax, Bcl-2, caspase 9, caspase 3, PARP, MMP-2, MMP-9, PI3K/p-PI3K, AKT/p-AKT, p38MAPK/p-p38 MAPK, ERK/p-ERK, LATS2, YAP, TAZ and TEAD1 were assessed by western blotting, respectively. Results: The bioactive components of CP inhibiting HepG2 cells were mainly flavonoids, and esters. CP induced HepG2 apoptosis through a mitochondrial-dependent intrinsic pathway with elevated the levels of cleaved PARP, cleaved caspase 3, and Bax and decreased the expressions of Bcl-2 and procaspase 9. It seemed that CP triggered apoptosis by activation of the p38 MAPK and inactivation of p-ERK. More importantly, we found that CP suppressed the Hippo pathway, leading to inactivation of YAP/TAZ and TEAD1 and inhibition of PI3K/AKT signaling molecules. Conclusion: CP exerted excellent anti-proliferation and pro-apoptosis actions in HepG2 cells by inactivation of the loop between the Hippo/YAP and PI3K/AKT pathways, and may be a promising therapy for HCC.
format	article
author	Hui Liu Junya Li Wenwen Yuan Shengyu Hao Meng Wang Fei Wang Hongzhuan Xuan
author_facet	Hui Liu Junya Li Wenwen Yuan Shengyu Hao Meng Wang Fei Wang Hongzhuan Xuan
author_sort	Hui Liu
title	Bioactive components and mechanisms of poplar propolis in inhibiting proliferation of human hepatocellular carcinoma HepG2 cells
title_short	Bioactive components and mechanisms of poplar propolis in inhibiting proliferation of human hepatocellular carcinoma HepG2 cells
title_full	Bioactive components and mechanisms of poplar propolis in inhibiting proliferation of human hepatocellular carcinoma HepG2 cells
title_fullStr	Bioactive components and mechanisms of poplar propolis in inhibiting proliferation of human hepatocellular carcinoma HepG2 cells
title_full_unstemmed	Bioactive components and mechanisms of poplar propolis in inhibiting proliferation of human hepatocellular carcinoma HepG2 cells
title_sort	bioactive components and mechanisms of poplar propolis in inhibiting proliferation of human hepatocellular carcinoma hepg2 cells
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/542a94f37c57478686c02fbda349d13b
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Bioactive components and mechanisms of poplar propolis in inhibiting proliferation of human hepatocellular carcinoma HepG2 cells

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