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

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.

Basic information

Original name

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

Name in Czech

Ferrocey jako kandidáti na nová protinádorová léčiva: Stanovení mechanismu účinku

Authors

SKOUPILOVÁ, Hana (203 Czech Republic), Martin BARTOŠÍK (703 Slovakia), Lucia SOMMEROVÁ (703 Slovakia), Jiří PINKAS, Tomáš VACULOVIČ (203 Czech Republic, belonging to the institution), Viktor KANICKÝ (203 Czech Republic, belonging to the institution), Jindřich KARBAN and Roman HRSTKA (203 Czech Republic, guarantor)

Edition

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

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

Netherlands

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.432

RIV identification code

RIV/00216224:14310/20:00115228

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1016/j.ejphar.2019.172825

UT WoS

000504024800004

Keywords (in Czech)

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

Keywords in English

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

Abstract

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.

Citovat

SKOUPILOVÁ, Hana, Martin BARTOŠÍK, Lucia SOMMEROVÁ, Jiří PINKAS, Tomáš VACULOVIČ, Viktor KANICKÝ, Jindřich KARBAN and Roman HRSTKA. Ferrocenes as new anticancer drug candidates: Determination of the mechanism of action. European Journal of Pharmacology. Amsterdam: Elsevier, 2020, vol. 867, JAN 15 2020, p. 1-8. ISSN 0014-2999. Available from: https://dx.doi.org/10.1016/j.ejphar.2019.172825.

@article{1608396,
   author = {Skoupilová, Hana and Bartošík, Martin and Sommerová, Lucia and Pinkas, Jiří and Vaculovič, Tomáš and Kanický, Viktor and Karban, Jindřich and Hrstka, Roman},
   article_location = {Amsterdam},
   article_number = {JAN 15 2020},
   doi = {http://dx.doi.org/10.1016/j.ejphar.2019.172825},
   keywords = {Cellular uptake; Ferrocene; Ovarian cancer; Reactive oxygen species; Transferrin; Transferrin receptor},
   language = {eng},
   issn = {0014-2999},
   journal = {European Journal of Pharmacology},
   title = {Ferrocenes as new anticancer drug candidates: Determination of the mechanism of action},
   url = {https://www.sciencedirect.com/science/article/pii/S0014299919307770?via%3Dihub},
   volume = {867},
   year = {2020}
}

TY  - JOUR
ID  - 1608396
AU  - Skoupilová, Hana - Bartošík, Martin - Sommerová, Lucia - Pinkas, Jiří - Vaculovič, Tomáš - Kanický, Viktor - Karban, Jindřich - Hrstka, Roman
PY  - 2020
TI  - Ferrocenes as new anticancer drug candidates: Determination of the mechanism of action
JF  - European Journal of Pharmacology
VL  - 867
IS  - JAN 15 2020
SP  - 1-8
EP  - 1-8
PB  - Elsevier
SN  - 00142999
KW  - Cellular uptake
KW  - Ferrocene
KW  - Ovarian cancer
KW  - Reactive oxygen species
KW  - Transferrin
KW  - Transferrin receptor
UR  - https://www.sciencedirect.com/science/article/pii/S0014299919307770?via%3Dihub
L2  - https://www.sciencedirect.com/science/article/pii/S0014299919307770?via%3Dihub
N2  - 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.
ER  -

SKOUPILOVÁ, Hana, Martin BARTOŠÍK, Lucia SOMMEROVÁ, Jiří PINKAS, Tomáš VACULOVIČ, Viktor KANICKÝ, Jindřich KARBAN and Roman HRSTKA. Ferrocenes as new anticancer drug candidates: Determination of the mechanism of action. \textit{European Journal of Pharmacology}. Amsterdam: Elsevier, 2020, vol.~867, JAN 15 2020, p.~1-8. ISSN~0014-2999. Available from: https://dx.doi.org/10.1016/j.ejphar.2019.172825.

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