Aurovertin B exerts potent antitumor activity against triple-negative breast cancer in vivo and in vitro via regulating ATP synthase activity and DUSP1 expression

被引:8
|
作者
Wu, Rui [1 ]
Yang, Xi [1 ]
Zhou, Qian [1 ]
Yu, Wenyan [1 ]
Li, Minwei [3 ]
Wo, Jianer [3 ]
Shan, Weiguang [1 ]
Zhao, Hong [4 ]
Chen, Yan [1 ,2 ]
Zhan, Zhajun [1 ]
机构
[1] Zhejiang Univ Technol, Coll Pharmaceut Sci, Hangzhou 310014, Peoples R China
[2] Zhejiang Univ Technol, Lab Anim Ctr, Hangzhou, Peoples R China
[3] Zhejiang Univ, Affiliated Hosp 1, Sch Med,State Key Lab Diag & Treatment Infect Dis, Collaborat Innovat Ctr Diag & Treatment Infect Di, Hangzhou, Peoples R China
[4] Zhejiang Chinese Med Univ, Affiliated Hosp, Hangzhou, Peoples R China
来源
PHARMAZIE | 2020年 / 75卷 / 06期
关键词
BIOENERGETIC SIGNATURE; MARKER; CELLS;
D O I
10.1691/ph.2020.0380
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Aurovertin B, a natural compound from Calcarisporium arbuscular, exhibits potent antiproliferative activity particularly against triple-negative breast cancer cells (TNBC), while having less cytotoxicity on normal breast cell MCF10A. However, very little is known about the in vivo antitumor activity of aurovertin B and the possible mechanism of the selective effect on triple-negative breast cancer cells. In this study, flow cytometry and DAPI staining analysis showed that aurovertin B treatment in human triple-negative breast cancer cell MDA-MB-231 could induce more apoptotic cells than taxol treatment group. Furthermore, the present study also revealed that aurovertin B induced apoptosis was due to regulation of ATP synthase activity rather than changes in gene expression. Interestingly, the cancer genome atlas (TCGA) data analysis implied that the expression level of DUSP1, a member of the dual-specificity phosphatases, was highly downregulated in breast tissue of TNBC patients compared with their adjacent normal tissues. Real-time PCR and western blot analyses further demonstrated that aurovertin B could dramatically increase mRNA and protein expression levels of DUSP1 in MDA-MB-231 cells but not in MCF10A cells. The potent anti-tumor activity of aurovertin B was further verified in a human MDA-MB-231 xenograft mouse model.
引用
收藏
页码:261 / 265
页数:5
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