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Protocatechuic Aldehyde Represses Proliferation and Migration of Breast Cancer Cells through Targeting C-terminal Binding Protein 1

文献类型：期刊论文

作者Deng, Yu1,2; Guo, Wanjun3; Li, Guancheng4; Li, Shuang5; Li, Hong6; Li, Xinyan7; Niu, Bei1; Song, Mingzhu1; Zhang, Yamei8; Xu, Zhijian9
刊名JOURNAL OF BREAST CANCER
出版日期2020-02-01
卷号23期号:1页码:20-35
关键词Breast neoplasms C-terminal binding protein Protocatechualdehyde
ISSN号1738-6756
DOI10.4048/jbc.2020.23.e7
通讯作者Li, Fulun(drlifulun@163.com)
英文摘要Purpose: C-terminal binding protein 1 (CtBP1) is a transcriptional co-repressor that is overexpressed in many cancers. CtBP1 transcriptionally represses a broad array of tumor suppressors, which promotes cancer cell proliferation, migration, invasion, and resistance to apoptosis. Recent studies have demonstrated that CtBP1 is a potential target for cancer therapy. This study was designed to screen for compounds that potentially target CtBP1. Methods: Using a structure-based virtual screening for CtBP1 inhibitors, we found protocatechuic aldehyde (PA), a natural compound found in the root of a traditional Chinese herb, Salvia miltiorrhiza, that directly binds to CtBP1. Microscale thermophoresis assay was performed to determine whether PA and CtBP1 directly bind to each other. Further, clustered regularly interspaced short palindromic repeats associated Cas9 nuclease-mediated CtBP1 knockout in breast cancer cells was used to validate the CtBP1 targeting specificity of PA. Results: Functional studies showed that PA repressed the proliferation and migration of breast cancer cells. Furthermore, PA elevated the expression of the downstream targets of CtBP1, p21 and E-cadherin, and decreased CtBP1 binding affinity for the promoter regions of p21 and E-cadherin in breast cancer cells. However, PA did not affect the expression of p21 and E-cadherin in the CtBP1 knockout breast cancer cells. In addition, the CtBP1 knockout breast cancer cells showed resistance to PA-induced repression of proliferation and migration. Conclusion: Our findings demonstrated that PA directly bound to CtBP1 and inhibited the growth and migration of breast cancer cells through CtBP1 inhibition. Structural modifications of PA are further required to enhance its binding affinity and selectivity for CtBP1.
WOS关键词COREPRESSOR ; CTBP ; TRANSCRIPTION ; INHIBITOR ; REDOX ; MELANOMA ; BRCA1
资助项目National Natural Science Foundation of China[81602652] ; National Natural Science Foundation of China[81673866] ; Shanghai Pudong New Area Health and Family Planning Commission[PWZxq2017-16] ; Education Department of Sichuan province[17ZA0095] ; National Key R&D Program of China[2016YFA0502800] ; Project of Shanghai University of Traditional Chinese Medicine[Y201865]
WOS研究方向Oncology
语种英语
WOS记录号WOS:000517765000003
出版者KOREAN BREAST CANCER SOC
源URL[http://119.78.100.183/handle/2S10ELR8/281348]  
专题中国科学院上海药物研究所
通讯作者Li, Fulun
作者单位1.Chengdu Univ, Sch Med, Chengdu, Peoples R China
2.Chengdu Univ, Inst Canc Biol & Drug Discovery, Chengdu, Peoples R China
3.Shanghai Univ Tradit Chinese Med, Dept Dermatol, Yueyang Hosp Integrated Tradit Chinese & Western, 110 Ganhe Rd, Shanghai 200437, Peoples R China
4.Shanghai Univ Tradit Chinese Med, Peoples Hosp 7, Shanghai, Peoples R China
5.Tianjin Acad Tradit Chinese Med, Dept Dermatol, Affiliated Hosp, Tianjin, Peoples R China
6.Univ Colorado Denver, Sch Med, Dept Dermatol, Aurora, CO USA
7.St Louis Univ, Dept Epidemiol & Biostat, Coll Publ Hlth & Social Justice, St Louis, MO 63103 USA
8.Chengdu Univeris Hosp, Cent Lab, Chengdu, Peoples R China
9.Chinese Acad Sci, CAS Key Lab Receptor Res, Drug Discovery & Design Ctr, Shanghai Inst Mat Med, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Deng, Yu,Guo, Wanjun,Li, Guancheng,et al. Protocatechuic Aldehyde Represses Proliferation and Migration of Breast Cancer Cells through Targeting C-terminal Binding Protein 1[J]. JOURNAL OF BREAST CANCER,2020,23(1):20-35.
APA Deng, Yu.,Guo, Wanjun.,Li, Guancheng.,Li, Shuang.,Li, Hong.,...&Li, Fulun.(2020).Protocatechuic Aldehyde Represses Proliferation and Migration of Breast Cancer Cells through Targeting C-terminal Binding Protein 1.JOURNAL OF BREAST CANCER,23(1),20-35.
MLA Deng, Yu,et al."Protocatechuic Aldehyde Represses Proliferation and Migration of Breast Cancer Cells through Targeting C-terminal Binding Protein 1".JOURNAL OF BREAST CANCER 23.1(2020):20-35.

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来源：上海药物研究所

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