| KUČÍRKOVÁ, Tereza, Marek STIBOREK, Monika DÚCKA, Jarmila NAVRÁTILOVÁ, Jelena BOGDANOVIČ PRISTOV, Ana POPOVIČ-BIJELIČ, Snežana VOJVODIČ, Jan PREISLER, Viktor KANICKÝ, Jan ŠMARDA, Ivan SPASOJEVIČ and Petr BENEŠ. Anti-cancer effects of wedelolactone: interactions with copper and subcellular localization. Metallomics. ROYAL SOC CHEMISTRY THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND, 2018, vol. 10, No 10, p. 1524-1531. ISSN 1756-5901. Available from: https://dx.doi.org/10.1039/c8mt00191j. |
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@article{1470428,
author = {Kučírková, Tereza and Stiborek, Marek and Dúcka, Monika and Navrátilová, Jarmila and Bogdanovič Pristov, Jelena and PopovičandBijelič, Ana and Vojvodič, Snežana and Preisler, Jan and Kanický, Viktor and Šmarda, Jan and Spasojevič, Ivan and Beneš, Petr},
article_number = {10},
doi = {http://dx.doi.org/10.1039/c8mt00191j},
keywords = {Breast cancer; copper; lysosome; redox interactions; wedelolactone},
language = {eng},
issn = {1756-5901},
journal = {Metallomics},
title = {Anti-cancer effects of wedelolactone: interactions with copper and subcellular localization},
url = {https://pubs.rsc.org/en/Content/ArticleLanding/2018/MT/C8MT00191J#!divAbstract},
volume = {10},
year = {2018}
}
TY - JOUR
ID - 1470428
AU - Kučírková, Tereza - Stiborek, Marek - Dúcka, Monika - Navrátilová, Jarmila - Bogdanovič Pristov, Jelena - Popovič-Bijelič, Ana - Vojvodič, Snežana - Preisler, Jan - Kanický, Viktor - Šmarda, Jan - Spasojevič, Ivan - Beneš, Petr
PY - 2018
TI - Anti-cancer effects of wedelolactone: interactions with copper and subcellular localization
JF - Metallomics
VL - 10
IS - 10
SP - 1524-1531
EP - 1524-1531
PB - ROYAL SOC CHEMISTRY THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND
SN - 17565901
KW - Breast cancer
KW - copper
KW - lysosome
KW - redox interactions
KW - wedelolactone
UR - https://pubs.rsc.org/en/Content/ArticleLanding/2018/MT/C8MT00191J#!divAbstract
N2 - Wedelactone (WL), a plant polyphenolic derivative of coumestan, represents a promising anti-cancer agent. The underlying mechanisms of its action are not fully understood and appear to involve interplay with copper ions. Herein, we examined coordination and redox interactions of WL with copper ions in phosphate buffer (pH 7), and in two breast cancer cell lines. EPR, UV-Vis and fluorescence spectroscopy showed that WL and copper ions build a coordination complex and distorted tetrahedral geometry. WL showed strong fluorescence that was quenched by copper ions. The sequestration of the intracellular copper pool with neocuproine led to a significant drop in the cytotoxic effects of WL, whereas the co-application of copper ions and WL and the formation of an extracellular complex suppressed both the cytotoxic effects of WL and copper loading. Fluorescence microscopy showed that WL is mainly localized in the cytosol and significantly less in the nuclei. WL fluorescence was stronger in cells pretreated with neocuproine, implying that the complex of WL and copper ions is formed inside the cells. WL caused a two-fold increase in the lysosomal level of copper as well as copper-dependent lysosome membrane permeabilization. On the other hand, the protective effects of overexpression of thioredoxin 1 imply that WL exerts the main oxidative impact inside the nucleus. The interactions of WL with copper may be essential for therapeutic performance and selectivity against cancer cells, taking into account that a number of cancer types, including breast cancer, exhibit increased intratumoral copper levels or altered copper distribution.
ER -
KUČÍRKOVÁ, Tereza, Marek STIBOREK, Monika DÚCKA, Jarmila NAVRÁTILOVÁ, Jelena BOGDANOVIČ PRISTOV, Ana POPOVIČ-BIJELIČ, Snežana VOJVODIČ, Jan PREISLER, Viktor KANICKÝ, Jan ŠMARDA, Ivan SPASOJEVIČ and Petr BENEŠ. Anti-cancer effects of wedelolactone: interactions with copper and subcellular localization. \textit{Metallomics}. ROYAL SOC CHEMISTRY THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND, 2018, vol.~10, No~10, p.~1524-1531. ISSN~1756-5901. Available from: https://dx.doi.org/10.1039/c8mt00191j.
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