Identifying the Effect of Ursolic Acid Against Triple-Negative Breast Cancer: Coupling Network Pharmacology With Experiments Verification

Triple negative breast cancer (TNBC) is a subtype of breast cancer with complex heterogeneity, high invasiveness, and long-term poor prognosis. With the development of molecular pathology and molecular genetics, the gene map of TNBC with distinctive biological characteristics has been outlined more...

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Autores principales:	Yubao Zhang, Xiaoran Ma, Huayao Li, Jing Zhuang, Fubin Feng, Lijuan Liu, Cun Liu, Changgang Sun
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	ursolic acid triple-negative breast cancer antiproliferative network pharmacology molecular docking Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/960a9398b2444583b15a023c2eb9e77d
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spelling	oai:doaj.org-article:960a9398b2444583b15a023c2eb9e77d2021-11-11T05:52:51ZIdentifying the Effect of Ursolic Acid Against Triple-Negative Breast Cancer: Coupling Network Pharmacology With Experiments Verification1663-981210.3389/fphar.2021.685773https://doaj.org/article/960a9398b2444583b15a023c2eb9e77d2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.685773/fullhttps://doaj.org/toc/1663-9812Triple negative breast cancer (TNBC) is a subtype of breast cancer with complex heterogeneity, high invasiveness, and long-term poor prognosis. With the development of molecular pathology and molecular genetics, the gene map of TNBC with distinctive biological characteristics has been outlined more clearly. Natural plant extracts such as paclitaxel, vinblastine, colchicine etc., have occupied an important position in the treatment of hormone-independent breast cancer. Ursolic acid (UA), a triterpenoid acid compound derived from apple, pear, loquat leaves, etc., has been reported to be effective in a variety of cancer treatments, but there are few reports on the treatment of TNBC. This study performed comprehensive bioinformatics analysis and in vitro experiments to identify the effect of UA on TNBC treatment and its potential molecular mechanism. Our results showed that UA could not only reduce the proliferation, migration, and invasion in MDA-MB-231 and MDA-MB-468 cell lines with a dose-dependent manner but also induce cell cycle arrest and apoptosis. Meanwhile, we collected the gene expression data GSE45827 and GSE65194 from GEO for comparison between TNBC and normal cell type and obtained 724 DEGs. Subsequently, PLK1 and CCNB1 related to TNBC were screened as the key targets via topological analysis and molecular docking, and gene set enrichment analysis identified the key pathway as the p53 signaling pathway. In addition, quantitative real-time PCR and western blot verified the key genes were PLK1 and CCNB1. In vivo and in vitro experiments showed that UA could inhibit the growth of TNBC cells, and down-regulate the protein expression levels of PLK1 and CCNB1 by mediating p53 signaling pathway. These findings provide strong evidence for UA intervention in TNBC via multi-target therapy.Yubao ZhangXiaoran MaHuayao LiJing ZhuangFubin FengLijuan LiuCun LiuChanggang SunChanggang SunFrontiers Media S.A.articleursolic acidtriple-negative breast cancerantiproliferativenetwork pharmacologymolecular dockingTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ursolic acid triple-negative breast cancer antiproliferative network pharmacology molecular docking Therapeutics. Pharmacology RM1-950
spellingShingle	ursolic acid triple-negative breast cancer antiproliferative network pharmacology molecular docking Therapeutics. Pharmacology RM1-950 Yubao Zhang Xiaoran Ma Huayao Li Jing Zhuang Fubin Feng Lijuan Liu Cun Liu Changgang Sun Changgang Sun Identifying the Effect of Ursolic Acid Against Triple-Negative Breast Cancer: Coupling Network Pharmacology With Experiments Verification
description	Triple negative breast cancer (TNBC) is a subtype of breast cancer with complex heterogeneity, high invasiveness, and long-term poor prognosis. With the development of molecular pathology and molecular genetics, the gene map of TNBC with distinctive biological characteristics has been outlined more clearly. Natural plant extracts such as paclitaxel, vinblastine, colchicine etc., have occupied an important position in the treatment of hormone-independent breast cancer. Ursolic acid (UA), a triterpenoid acid compound derived from apple, pear, loquat leaves, etc., has been reported to be effective in a variety of cancer treatments, but there are few reports on the treatment of TNBC. This study performed comprehensive bioinformatics analysis and in vitro experiments to identify the effect of UA on TNBC treatment and its potential molecular mechanism. Our results showed that UA could not only reduce the proliferation, migration, and invasion in MDA-MB-231 and MDA-MB-468 cell lines with a dose-dependent manner but also induce cell cycle arrest and apoptosis. Meanwhile, we collected the gene expression data GSE45827 and GSE65194 from GEO for comparison between TNBC and normal cell type and obtained 724 DEGs. Subsequently, PLK1 and CCNB1 related to TNBC were screened as the key targets via topological analysis and molecular docking, and gene set enrichment analysis identified the key pathway as the p53 signaling pathway. In addition, quantitative real-time PCR and western blot verified the key genes were PLK1 and CCNB1. In vivo and in vitro experiments showed that UA could inhibit the growth of TNBC cells, and down-regulate the protein expression levels of PLK1 and CCNB1 by mediating p53 signaling pathway. These findings provide strong evidence for UA intervention in TNBC via multi-target therapy.
format	article
author	Yubao Zhang Xiaoran Ma Huayao Li Jing Zhuang Fubin Feng Lijuan Liu Cun Liu Changgang Sun Changgang Sun
author_facet	Yubao Zhang Xiaoran Ma Huayao Li Jing Zhuang Fubin Feng Lijuan Liu Cun Liu Changgang Sun Changgang Sun
author_sort	Yubao Zhang
title	Identifying the Effect of Ursolic Acid Against Triple-Negative Breast Cancer: Coupling Network Pharmacology With Experiments Verification
title_short	Identifying the Effect of Ursolic Acid Against Triple-Negative Breast Cancer: Coupling Network Pharmacology With Experiments Verification
title_full	Identifying the Effect of Ursolic Acid Against Triple-Negative Breast Cancer: Coupling Network Pharmacology With Experiments Verification
title_fullStr	Identifying the Effect of Ursolic Acid Against Triple-Negative Breast Cancer: Coupling Network Pharmacology With Experiments Verification
title_full_unstemmed	Identifying the Effect of Ursolic Acid Against Triple-Negative Breast Cancer: Coupling Network Pharmacology With Experiments Verification
title_sort	identifying the effect of ursolic acid against triple-negative breast cancer: coupling network pharmacology with experiments verification
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/960a9398b2444583b15a023c2eb9e77d
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Identifying the Effect of Ursolic Acid Against Triple-Negative Breast Cancer: Coupling Network Pharmacology With Experiments Verification

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