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Pregled bibliografske jedinice broj: 951855

Biological Activity of Flavonoids and Rare Sesquiterpene Lactones Isolated From Centaurea ragusina L.


Grienke, Ulrike; Radić Brkanac, Sandra; Vujčić, Valerija; Urban, Ernst; Ivanković, Siniša; Stojković, Ranko; Rollinger, Judith M.; Kralj, Juran; Brozović, Anamaria; Radić Stojković, Marijana
Biological Activity of Flavonoids and Rare Sesquiterpene Lactones Isolated From Centaurea ragusina L. // Frontiers in Pharmacology, 9 (2018), 972, 15 doi:10.3389/fphar.2018.00972 (međunarodna recenzija, članak, znanstveni)


Naslov
Biological Activity of Flavonoids and Rare Sesquiterpene Lactones Isolated From Centaurea ragusina L.

Autori
Grienke, Ulrike ; Radić Brkanac, Sandra ; Vujčić, Valerija ; Urban, Ernst ; Ivanković, Siniša ; Stojković, Ranko ; Rollinger, Judith M. ; Kralj, Juran ; Brozović, Anamaria ; Radić Stojković, Marijana

Izvornik
Frontiers in Pharmacology (1663-9812) 9 (2018); 972, 15

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Centaurea, sesquiterpene lactones, DNA, cell viability, toxicity, glutathione

Sažetak
The endemic Croatian species Centaurea ragusina L., like other species from the genus Centaurea, has been traditionally used in Croatia as an antibacterial agent and for the treatment of gastrointestinal and urogenital disorders. In several chromatographic steps, three flavonoids and three sesquiterpene lactones (STLs) were isolated and identified from the most active fractions of the ethanol extract. Two STLs, one for which we created the trivial name ragusinin, and hemistepsin A are here reported for the first time as constituents of the genus Centaurea. All six compounds were screened for their effect on several tumor and one normal cell lines. Among them, ragusinin showed the best bioactivity and high specificity to affect tumor murine SCCVII, human HeLa and Caco-2 cell lines, but not the viability of normal V79 fibroblasts. Due to these characteristics the action of ragusinin was investigated in more detail. Since DNA is the primary target for many drugs with antibacterial and anticancer activity, we studied its interaction with ragusinin. Rather moderate binding affinity to DNA excluded it as the primary target of ragusinin. Due to the possibility of STL interaction with glutathione (GSH), the ubiquitous peptide that traps reactive compounds and other xenobiotics to prevent damage to vital proteins and nucleic acids, its role in deactivation of ragusinin was evaluated. Addition of the GSH precursor N- acetyl-cysteine potentiated the viability of HeLa cells, while the addition of GSH inhibitor L-buthionine sulfoximine decreased it. Moreover, pre-treatment of HeLa cells with the inhibitor of glutathione-S-transferase decreased their viability indicating the detoxifying role of GSH in ragusinin treated cells. Cell death, derived by an accumulation of cells in a G2 phase of the cell cylce, was shown to be independent of poly (ADP-ribose) polymerase and caspase-3 cleavage pointing toward an alternative cell death pathway.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija, Farmacija



POVEZANOST RADA


Projekt / tema
European Social Fund 2007–2013
HR.3.2.01-0290
HRZZ-IP-2013-11-1477 - Višenamjensko očitavanje DNA / RNA sekundarne strukture molekularnim kemijskim senzorima (Ivo Piantanida, )
HRZZ-IP-2016-06-1036 - Određivanje ključnih molekula epitelno-mezenhimalne tranzicije kao mogućih ciljeva za terapiju raka jajnika (Anamaria Brozović, )

Ustanove
Institut "Ruđer Bošković", Zagreb,
Prirodoslovno-matematički fakultet, Zagreb,
Sveučilište u Zagrebu

Časopis indeksira:


  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


Uključenost u ostale bibliografske baze podataka:


  • DOAJ
  • CrossRef
  • Google Scholar


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