Next Article in Journal
The Neutrophil/Lymphocyte Ratio at Diagnosis Is Significantly Associated with Survival in Metastatic Pancreatic Cancer Patients
Next Article in Special Issue
Acteoside and Isoacteoside Protect Amyloid β Peptide Induced Cytotoxicity, Cognitive Deficit and Neurochemical Disturbances In Vitro and In Vivo
Previous Article in Journal
Inhibition or Stimulation of Autophagy Affects Early Formation of Lipofuscin-Like Autofluorescence in the Retinal Pigment Epithelium Cell
Previous Article in Special Issue
Biosynthesis of α-Glucosidase Inhibitors by a Newly Isolated Bacterium, Paenibacillus sp. TKU042 and Its Effect on Reducing Plasma Glucose in a Mouse Model
Article Menu
Issue 4 (April) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2017, 18(4), 729; doi:10.3390/ijms18040729

Wedelolactone Acts as Proteasome Inhibitor in Breast Cancer Cells

1
Laboratory of Cell Differentiation, Department of Experimental Biology, Faculty of Science, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic
2
International Clinical Research Center, Center for Biological and Cellular Engineering, St. Anne’s University Hospital, Pekarska 53, 656 91 Brno, Czech Republic
3
Loschmidt Laboratories, Department of Experimental Biology and Research Centre for Toxic Compounds in the Environment RECETOX, Faculty of Science, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic
4
Department of Chemistry, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic
5
CEITEC-Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic
6
Department of Life Sciences, Institute for Multidisciplinary Research, University of Belgrade, 11030 Belgrade, Serbia
*
Author to whom correspondence should be addressed.
Academic Editor: Toshio Morikawa
Received: 1 February 2017 / Revised: 20 March 2017 / Accepted: 25 March 2017 / Published: 29 March 2017
(This article belongs to the Special Issue Biological Activity of Natural Secondary Metabolite Products)
View Full-Text   |   Download PDF [4674 KB, uploaded 29 March 2017]   |  

Abstract

Wedelolactone is a multi-target natural plant coumestan exhibiting cytotoxicity towards cancer cells. Although several molecular targets of wedelolactone have been recognized, the molecular mechanism of its cytotoxicity has not yet been elucidated. In this study, we show that wedelolactone acts as an inhibitor of chymotrypsin-like, trypsin-like, and caspase-like activities of proteasome in breast cancer cells. The proteasome inhibitory effect of wedelolactone was documented by (i) reduced cleavage of fluorogenic proteasome substrates; (ii) accumulation of polyubiquitinated proteins and proteins with rapid turnover in tumor cells; and (iii) molecular docking of wedelolactone into the active sites of proteasome catalytic subunits. Inhibition of proteasome by wedelolactone was independent on its ability to induce reactive oxygen species production by redox cycling with copper ions, suggesting that wedelolactone acts as copper-independent proteasome inhibitor. We conclude that the cytotoxicity of wedelolactone to breast cancer cells is partially mediated by targeting proteasomal protein degradation pathway. Understanding the structural basis for inhibitory mode of wedelolactone might help to open up new avenues for design of novel compounds efficiently inhibiting cancer cells. View Full-Text
Keywords: breast cancer; copper; proteasome; reactive oxygen species; wedelolactone breast cancer; copper; proteasome; reactive oxygen species; wedelolactone
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Nehybová, T.; Šmarda, J.; Daniel, L.; Stiborek, M.; Kanický, V.; Spasojevič, I.; Preisler, J.; Damborský, J.; Beneš, P. Wedelolactone Acts as Proteasome Inhibitor in Breast Cancer Cells. Int. J. Mol. Sci. 2017, 18, 729.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top