• Something wrong with this record ?

Anti-cancer effects of wedelolactone: interactions with copper and subcellular localization

T. Kučírková, M. Stiborek, M. Dúcka, J. Navrátilová, J. Bogdanović Pristov, A. Popović-Bijelić, S. Vojvodić, J. Preisler, V. Kanický, J. Šmarda, I. Spasojević, P. Beneš,

. 2018 ; 10 (10) : 1524-1531. [pub] 20180921

Language English Country England, Great Britain

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc19035010

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 Cu2+ in phosphate buffer (pH 7), and in two breast cancer cell lines. EPR, UV-Vis and fluorescence spectroscopy showed that WL and Cu2+ build a coordination complex with 2 : 1 stoichiometry and distorted tetrahedral geometry. WL showed strong fluorescence that was quenched by Cu2+. 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 Cu2+ 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 Cu2+ 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.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc19035010
003      
CZ-PrNML
005      
20240321140334.0
007      
ta
008      
191007s2018 enk f 000 0|eng||
009      
AR
024    7_
$a 10.1039/c8mt00191j $2 doi
035    __
$a (PubMed)30238942
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a enk
100    1_
$a Kučírková, Tereza $u Department of Experimental Biology, Faculty of Science, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic. pbenes@sci.muni.cz and International Clinical Research Center, Center for Biological and Cellular Engineering, St. Anne's University Hospital, Pekarska 53, 65691 Brno, Czech Republic.
245    10
$a Anti-cancer effects of wedelolactone: interactions with copper and subcellular localization / $c T. Kučírková, M. Stiborek, M. Dúcka, J. Navrátilová, J. Bogdanović Pristov, A. Popović-Bijelić, S. Vojvodić, J. Preisler, V. Kanický, J. Šmarda, I. Spasojević, P. Beneš,
520    9_
$a 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 Cu2+ in phosphate buffer (pH 7), and in two breast cancer cell lines. EPR, UV-Vis and fluorescence spectroscopy showed that WL and Cu2+ build a coordination complex with 2 : 1 stoichiometry and distorted tetrahedral geometry. WL showed strong fluorescence that was quenched by Cu2+. 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 Cu2+ 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 Cu2+ 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.
650    _2
$a protinádorové látky $x farmakologie $7 D000970
650    _2
$a apoptóza $7 D017209
650    _2
$a nádory prsu $x farmakoterapie $x metabolismus $x patologie $7 D001943
650    _2
$a komplexní sloučeniny $x metabolismus $7 D056831
650    _2
$a měď $x metabolismus $7 D003300
650    _2
$a kumariny $x farmakologie $7 D003374
650    _2
$a ženské pohlaví $7 D005260
650    _2
$a lidé $7 D006801
650    _2
$a subcelulární frakce $x metabolismus $7 D013347
650    _2
$a nádorové buňky kultivované $7 D014407
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Stiborek, Marek $u Department of Chemistry, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic.
700    1_
$a Dúcka, Monika $u Department of Experimental Biology, Faculty of Science, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic. pbenes@sci.muni.cz and International Clinical Research Center, Center for Biological and Cellular Engineering, St. Anne's University Hospital, Pekarska 53, 65691 Brno, Czech Republic. $7 xx0315288
700    1_
$a Navrátilová, Jarmila $u Department of Experimental Biology, Faculty of Science, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic. pbenes@sci.muni.cz and International Clinical Research Center, Center for Biological and Cellular Engineering, St. Anne's University Hospital, Pekarska 53, 65691 Brno, Czech Republic.
700    1_
$a Bogdanović Pristov, Jelena $u Department of Life Sciences, Institute for Multidisciplinary Research, University of Belgrade, Kneza Višeslava 1, 11030, Belgrade, Serbia. redoxsci@gmail.com.
700    1_
$a Popović-Bijelić, Ana $u EPR Laboratory, Faculty of Physical Chemistry, University of Belgrade, Studentski trg 12-16, 11158, Belgrade, Serbia.
700    1_
$a Vojvodić, SneŽana $u Department of Life Sciences, Institute for Multidisciplinary Research, University of Belgrade, Kneza Višeslava 1, 11030, Belgrade, Serbia. redoxsci@gmail.com.
700    1_
$a Preisler, Jan $u Department of Chemistry, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic and CEITEC-Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic.
700    1_
$a Kanický, Viktor $u Department of Chemistry, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic and CEITEC-Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic.
700    1_
$a Šmarda, Jan $u Department of Experimental Biology, Faculty of Science, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic. pbenes@sci.muni.cz.
700    1_
$a Spasojević, Ivan $u Department of Life Sciences, Institute for Multidisciplinary Research, University of Belgrade, Kneza Višeslava 1, 11030, Belgrade, Serbia. redoxsci@gmail.com.
700    1_
$a Beneš, Petr $u Department of Experimental Biology, Faculty of Science, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic. pbenes@sci.muni.cz and International Clinical Research Center, Center for Biological and Cellular Engineering, St. Anne's University Hospital, Pekarska 53, 65691 Brno, Czech Republic.
773    0_
$w MED00181644 $t Metallomics $x 1756-591X $g Roč. 10, č. 10 (2018), s. 1524-1531
856    41
$u https://pubmed.ncbi.nlm.nih.gov/30238942 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20191007 $b ABA008
991    __
$a 20240321140327 $b ABA008
999    __
$a ok $b bmc $g 1451670 $s 1073560
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2018 $b 10 $c 10 $d 1524-1531 $e 20180921 $i 1756-591X $m Metallomics $n Metallomics $x MED00181644
LZP    __
$a Pubmed-20191007

Find record

Citation metrics

Archiving options