2018
Anti-cancer effects of wedelolactone: interactions with copper and subcellular localization
KUČÍRKOVÁ, Tereza, Marek STIBOREK, Monika DÚCKA, Jarmila NAVRÁTILOVÁ, Jelena BOGDANOVIČ PRISTOV et. al.Základní údaje
Originální název
Anti-cancer effects of wedelolactone: interactions with copper and subcellular localization
Autoři
KUČÍRKOVÁ, Tereza (203 Česká republika, domácí), Marek STIBOREK (203 Česká republika, domácí), Monika DÚCKA (703 Slovensko, domácí), Jarmila NAVRÁTILOVÁ (203 Česká republika, domácí), Jelena BOGDANOVIČ PRISTOV (688 Srbsko), Ana POPOVIČ-BIJELIČ (688 Srbsko), Snežana VOJVODIČ (688 Srbsko), Jan PREISLER (203 Česká republika, domácí), Viktor KANICKÝ (203 Česká republika, domácí), Jan ŠMARDA (203 Česká republika, domácí), Ivan SPASOJEVIČ (688 Srbsko) a Petr BENEŠ (203 Česká republika, garant, domácí)
Vydání
Metallomics, ROYAL SOC CHEMISTRY THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND, 2018, 1756-5901
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Obor
10601 Cell biology
Stát vydavatele
Velká Británie a Severní Irsko
Utajení
není předmětem státního či obchodního tajemství
Odkazy
Impakt faktor
Impact factor: 3.571
Kód RIV
RIV/00216224:14310/18:00101363
Organizační jednotka
Přírodovědecká fakulta
UT WoS
000448343400014
Klíčová slova anglicky
Breast cancer; copper; lysosome; redox interactions; wedelolactone
Štítky
Příznaky
Mezinárodní význam, Recenzováno
Změněno: 23. 4. 2024 12:42, Mgr. Michal Petr
Anotace
V originále
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.
Návaznosti
GA18-16583S, projekt VaV |
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MUNI/A/0824/2017, interní kód MU |
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MUNI/G/0974/2016, interní kód MU |
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