J 2020

Ferrocenes as new anticancer drug candidates: Determination of the mechanism of action

SKOUPILOVÁ, Hana; Martin BARTOŠÍK; Lucia SOMMEROVÁ; Jiří PINKAS; Tomáš VACULOVIČ et al.

Základní údaje

Originální název

Ferrocenes as new anticancer drug candidates: Determination of the mechanism of action

Název česky

Ferrocey jako kandidáti na nová protinádorová léčiva: Stanovení mechanismu účinku

Autoři

SKOUPILOVÁ, Hana; Martin BARTOŠÍK; Lucia SOMMEROVÁ; Jiří PINKAS; Tomáš VACULOVIČ; Viktor KANICKÝ; Jindřich KARBAN a Roman HRSTKA

Vydání

European Journal of Pharmacology, Amsterdam, Elsevier, 2020, 0014-2999

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30104 Pharmacology and pharmacy

Stát vydavatele

Nizozemské království

Utajení

není předmětem státního či obchodního tajemství

Odkazy

Impakt faktor

Impact factor: 4.432

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/20:00115228

Organizační jednotka

Přírodovědecká fakulta

UT WoS

000504024800004

EID Scopus

2-s2.0-85075851969

Klíčová slova česky

Buněčný příjem; Ferroceny; Rakovina vaječníků; Reaktivní kyslíkové radikály; Transferrinový receptor

Klíčová slova anglicky

Cellular uptake; Ferrocene; Ovarian cancer; Reactive oxygen species; Transferrin; Transferrin receptor

Štítky

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 23. 11. 2020 16:10, Mgr. Marie Novosadová Šípková, DiS.

Anotace

V originále

Chemotherapy plays an essential role in the management of cancer worldwide. However, it is a non-specific treatment limited by major drawbacks, thus identification and testing of new promising molecular structures representing potential drug candidates are urgently needed. In this work, ferrocene complexes as potential antitumor drugs that display cytotoxicity in low micromolar concentrations against ovarian cancer cells A2780 and SK-OV-3 were investigated to identify their mode of action. Their mechanism of cellular accumulation was studied using differential pulse voltammetry and inductively coupled plasma - mass spectrometry. Their mode of cell death induction was determined by changes in the mitochondrial membrane potential, production of reactive oxygen species and by Annexin V staining. Transferrin receptors were identified as key mediators of intracellular accumulation of ferrocenes and the extent of cellular uptake reflected the anticancer activity of individual compounds. Functional analysis revealed activation of intrinsic apoptosis as a dominant mechanism leading to regulated cell death induced in ovarian cancer cells by ferrocenes. Ferrocenes represent a group of promising sandwich organometallic complexes exerting cytotoxic activity. We suggest their application not only as standalone chemotherapeutics but also as modifying substituents of known drugs to improve their antitumor effects.