β-lapachone suppresses tumour progression by inhibiting epithelial-to-mesenchymal transition in NQO1-positive breast cancers

Abstract NQO1 is a FAD-binding protein that can form homodimers and reduce quinones to hydroquinones, and a growing body of evidence currently suggests that NQO1 is dramatically elevated in solid cancers. Here, we demonstrated that NQO1 was elevated in breast cancer and that its expression level was...

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Main Authors: Yang Yang, Xianchun Zhou, Ming Xu, Junjie Piao, Yuan Zhang, Zhenhua Lin, Liyan Chen
Format: Article
Language:English
Published: Nature Publishing Group 2017-06-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-017-02937-0
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spelling doaj-dac6f61bcecb4c01adddd2d0c7f7a1f92020-12-08T01:14:56ZengNature Publishing GroupScientific Reports2045-23222017-06-017111310.1038/s41598-017-02937-0β-lapachone suppresses tumour progression by inhibiting epithelial-to-mesenchymal transition in NQO1-positive breast cancersYang Yang0Xianchun Zhou1Ming Xu2Junjie Piao3Yuan Zhang4Zhenhua Lin5Liyan Chen6Department of Pathology & Cancer Research Center, Yanbian University Medical CollegeDepartment of Internal Medicine, Yanbian University HospitalDepartment of Pathology & Cancer Research Center, Yanbian University Medical CollegeDepartment of Pathology & Cancer Research Center, Yanbian University Medical CollegeDepartment of Pathology & Cancer Research Center, Yanbian University Medical CollegeDepartment of Pathology & Cancer Research Center, Yanbian University Medical CollegeDepartment of Pathology & Cancer Research Center, Yanbian University Medical CollegeAbstract NQO1 is a FAD-binding protein that can form homodimers and reduce quinones to hydroquinones, and a growing body of evidence currently suggests that NQO1 is dramatically elevated in solid cancers. Here, we demonstrated that NQO1 was elevated in breast cancer and that its expression level was positively correlated with invasion and reduced disease free survival (DFS) and overall survival (OS) rates. Next, we found that β-lapachone exerted significant anti-proliferation and anti-metastasis effects in breast cancer cell lines due to its effects on NQO1 expression. Moreover, we revealed that the anti-cancer effects of β-lapachone were mediated by the inactivation of the Akt/mTOR pathway. In conclusion, these results demonstrated that NQO1 could be a useful prognostic biomarker for patients with breast cancer, and its bioactivatable drug, β-lapachone represented a promising new development and an effective strategy for indicating the progression of NQO1-positive breast cancers.https://doi.org/10.1038/s41598-017-02937-0
collection DOAJ
language English
format Article
sources DOAJ
author Yang Yang
Xianchun Zhou
Ming Xu
Junjie Piao
Yuan Zhang
Zhenhua Lin
Liyan Chen
spellingShingle Yang Yang
Xianchun Zhou
Ming Xu
Junjie Piao
Yuan Zhang
Zhenhua Lin
Liyan Chen
β-lapachone suppresses tumour progression by inhibiting epithelial-to-mesenchymal transition in NQO1-positive breast cancers
Scientific Reports
author_facet Yang Yang
Xianchun Zhou
Ming Xu
Junjie Piao
Yuan Zhang
Zhenhua Lin
Liyan Chen
author_sort Yang Yang
title β-lapachone suppresses tumour progression by inhibiting epithelial-to-mesenchymal transition in NQO1-positive breast cancers
title_short β-lapachone suppresses tumour progression by inhibiting epithelial-to-mesenchymal transition in NQO1-positive breast cancers
title_full β-lapachone suppresses tumour progression by inhibiting epithelial-to-mesenchymal transition in NQO1-positive breast cancers
title_fullStr β-lapachone suppresses tumour progression by inhibiting epithelial-to-mesenchymal transition in NQO1-positive breast cancers
title_full_unstemmed β-lapachone suppresses tumour progression by inhibiting epithelial-to-mesenchymal transition in NQO1-positive breast cancers
title_sort β-lapachone suppresses tumour progression by inhibiting epithelial-to-mesenchymal transition in nqo1-positive breast cancers
publisher Nature Publishing Group
series Scientific Reports
issn 2045-2322
publishDate 2017-06-01
description Abstract NQO1 is a FAD-binding protein that can form homodimers and reduce quinones to hydroquinones, and a growing body of evidence currently suggests that NQO1 is dramatically elevated in solid cancers. Here, we demonstrated that NQO1 was elevated in breast cancer and that its expression level was positively correlated with invasion and reduced disease free survival (DFS) and overall survival (OS) rates. Next, we found that β-lapachone exerted significant anti-proliferation and anti-metastasis effects in breast cancer cell lines due to its effects on NQO1 expression. Moreover, we revealed that the anti-cancer effects of β-lapachone were mediated by the inactivation of the Akt/mTOR pathway. In conclusion, these results demonstrated that NQO1 could be a useful prognostic biomarker for patients with breast cancer, and its bioactivatable drug, β-lapachone represented a promising new development and an effective strategy for indicating the progression of NQO1-positive breast cancers.
url https://doi.org/10.1038/s41598-017-02937-0
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