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Aurovertin B exerts potent antitumor activity against triple-negative breast cancer in vivo and in vitro via regulating ATP synthase activity and DUSP1 expression.
- Source :
-
Die Pharmazie [Pharmazie] 2020 Jun 01; Vol. 75 (6), pp. 261-265. - Publication Year :
- 2020
-
Abstract
- 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.
- Subjects :
- Animals
Cell Line, Tumor
Cell Proliferation drug effects
Dual Specificity Phosphatase 1 genetics
Female
Gene Expression Regulation, Neoplastic
Humans
Mice
Mice, Nude
Mitochondrial Proton-Translocating ATPases metabolism
Triple Negative Breast Neoplasms genetics
Triple Negative Breast Neoplasms pathology
Xenograft Model Antitumor Assays
Antineoplastic Agents pharmacology
Apoptosis drug effects
Aurovertins pharmacology
Triple Negative Breast Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 0031-7144
- Volume :
- 75
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Die Pharmazie
- Publication Type :
- Academic Journal
- Accession number :
- 32539922
- Full Text :
- https://doi.org/10.1691/ph.2020.0380