Anti-cancer effects of wedelolactone: interactions with copper and subcellular localization
Samo za registrovane korisnike
2018
Autori
Kucirkova, TerezaStiborek, Marek
Ducka, Monika
Navratilova, Jarmila

Bogdanović Pristov, Jelena

Popovic-Bijelic, Ana

Vojvodić, Snežana

Preisler, Jan

Kanicky, Viktor
Smarda, Jan
Spasojević, Ivan

Benes, Petr

Članak u časopisu (Objavljena verzija)

Metapodaci
Prikaz svih podataka o dokumentuApstrakt
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 pre...treated 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.
Ključne reči:
plant polyphenolic derivative / copper ion / breast cancer cell lines / coordination complex / anti-cancer agent / EPRIzvor:
Metallomics, 2018, 10, 10, 1524-1531Izdavač:
- Royal Soc Chemistry, Cambridge
Finansiranje / projekti:
- Ispitivanja odnosa struktura-funkcija u ćelijskom zidu biljaka i izmene strukture zida enzimskim inženjeringom (RS-173017)
- National Program of Sustainability II (MEYS Czech Republic) [LQ1605]
- Czech Science FoundationGrant Agency of the Czech Republic [18-16583S]
- Grant Agency of the Masaryk University [MUNI/G/0974/2016, MUNI/A/0824/2017]
DOI: 10.1039/c8mt00191j
ISSN: 1756-5901
PubMed: 30238942
WoS: 000448343400014
Scopus: 2-s2.0-85055078004
Institucija/grupa
Institut za multidisciplinarna istraživanjaTY - JOUR AU - Kucirkova, Tereza AU - Stiborek, Marek AU - Ducka, Monika AU - Navratilova, Jarmila AU - Bogdanović Pristov, Jelena AU - Popovic-Bijelic, Ana AU - Vojvodić, Snežana AU - Preisler, Jan AU - Kanicky, Viktor AU - Smarda, Jan AU - Spasojević, Ivan AU - Benes, Petr PY - 2018 UR - http://rimsi.imsi.bg.ac.rs/handle/123456789/1156 AB - 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. PB - Royal Soc Chemistry, Cambridge T2 - Metallomics T1 - Anti-cancer effects of wedelolactone: interactions with copper and subcellular localization EP - 1531 IS - 10 SP - 1524 VL - 10 DO - 10.1039/c8mt00191j ER -
@article{ author = "Kucirkova, Tereza and Stiborek, Marek and Ducka, Monika and Navratilova, Jarmila and Bogdanović Pristov, Jelena and Popovic-Bijelic, Ana and Vojvodić, Snežana and Preisler, Jan and Kanicky, Viktor and Smarda, Jan and Spasojević, Ivan and Benes, Petr", year = "2018", abstract = "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.", publisher = "Royal Soc Chemistry, Cambridge", journal = "Metallomics", title = "Anti-cancer effects of wedelolactone: interactions with copper and subcellular localization", pages = "1531-1524", number = "10", volume = "10", doi = "10.1039/c8mt00191j" }
Kucirkova, T., Stiborek, M., Ducka, M., Navratilova, J., Bogdanović Pristov, J., Popovic-Bijelic, A., Vojvodić, S., Preisler, J., Kanicky, V., Smarda, J., Spasojević, I.,& Benes, P.. (2018). Anti-cancer effects of wedelolactone: interactions with copper and subcellular localization. in Metallomics Royal Soc Chemistry, Cambridge., 10(10), 1524-1531. https://doi.org/10.1039/c8mt00191j
Kucirkova T, Stiborek M, Ducka M, Navratilova J, Bogdanović Pristov J, Popovic-Bijelic A, Vojvodić S, Preisler J, Kanicky V, Smarda J, Spasojević I, Benes P. Anti-cancer effects of wedelolactone: interactions with copper and subcellular localization. in Metallomics. 2018;10(10):1524-1531. doi:10.1039/c8mt00191j .
Kucirkova, Tereza, Stiborek, Marek, Ducka, Monika, Navratilova, Jarmila, Bogdanović Pristov, Jelena, Popovic-Bijelic, Ana, Vojvodić, Snežana, Preisler, Jan, Kanicky, Viktor, Smarda, Jan, Spasojević, Ivan, Benes, Petr, "Anti-cancer effects of wedelolactone: interactions with copper and subcellular localization" in Metallomics, 10, no. 10 (2018):1524-1531, https://doi.org/10.1039/c8mt00191j . .