PMID- 34700230 OWN - NLM STAT- MEDLINE DCOM- 20220125 LR - 20220125 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 144 DP - 2021 Dec TI - Bioactive components and mechanisms of poplar propolis in inhibiting proliferation of human hepatocellular carcinoma HepG2 cells. PG - 112364 LID - S0753-3322(21)01148-3 [pii] LID - 10.1016/j.biopha.2021.112364 [doi] AB - 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. CI - Copyright (c) 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved. FAU - Liu, Hui AU - Liu H AD - School of Life Science, Liaocheng University, Liaocheng 252059, China. FAU - Li, Junya AU - Li J AD - School of Life Science, Liaocheng University, Liaocheng 252059, China. FAU - Yuan, Wenwen AU - Yuan W AD - School of Life Science, Liaocheng University, Liaocheng 252059, China. FAU - Hao, Shengyu AU - Hao S AD - School of Physical Science and Information Technology, Liaocheng University, Liaocheng 252059, China. FAU - Wang, Meng AU - Wang M AD - School of Life Science, Liaocheng University, Liaocheng 252059, China. FAU - Wang, Fei AU - Wang F AD - School of Life Science, Liaocheng University, Liaocheng 252059, China. FAU - Xuan, Hongzhuan AU - Xuan H AD - School of Life Science, Liaocheng University, Liaocheng 252059, China. Electronic address: hongzhuanxuan@163.com. LA - eng PT - Journal Article DEP - 20211023 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (Antineoplastic Agents) RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (YAP-Signaling Proteins) RN - 0 (YAP1 protein, human) RN - 9009-62-5 (Propolis) RN - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Antineoplastic Agents/isolation & purification/*pharmacology MH - Apoptosis/drug effects MH - Apoptosis Regulatory Proteins/metabolism MH - Carcinoma, Hepatocellular/*drug therapy/pathology MH - Cell Movement/drug effects MH - Cell Proliferation/*drug effects MH - Hep G2 Cells MH - Hippo Signaling Pathway MH - Humans MH - Liver Neoplasms/*drug therapy/pathology MH - Mitochondria/drug effects/metabolism/pathology MH - Phosphatidylinositol 3-Kinase/metabolism MH - *Populus MH - *Propolis/chemistry MH - Proto-Oncogene Proteins c-akt/metabolism MH - YAP-Signaling Proteins/metabolism OTO - NOTNLM OT - Apoptosis OT - Hepatocellular carcinoma OT - Hippo/YAP pathway OT - PI3K/AKT pathway OT - Poplar propolis EDAT- 2021/10/27 06:00 MHDA- 2022/01/27 06:00 CRDT- 2021/10/26 20:26 PHST- 2021/05/08 00:00 [received] PHST- 2021/10/17 00:00 [revised] PHST- 2021/10/19 00:00 [accepted] PHST- 2021/10/27 06:00 [pubmed] PHST- 2022/01/27 06:00 [medline] PHST- 2021/10/26 20:26 [entrez] AID - S0753-3322(21)01148-3 [pii] AID - 10.1016/j.biopha.2021.112364 [doi] PST - ppublish SO - Biomed Pharmacother. 2021 Dec;144:112364. doi: 10.1016/j.biopha.2021.112364. Epub 2021 Oct 23.