Anticancer potential of diiron thiocarbyne complexes
2023
Preuzimanje 🢃
Autori:
Mihajlović, EkatarinaJelača, Sanja
Biancalana, Lorenzo
Chiaverini, Lorenzo
Dojčinović, Biljana
Mijatović, Sanja
Zacchini, Stefano
Marchetti, Fabio
Maksimović-Ivanić, Danijela
Ostala autorstva
Spasojević, IvanTip dokumenta:
Konferencijski prilog (Objavljena verzija)
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© 2023 by the Faculty of Chemistry, University of Belgrade
Metapodaci
Prikaz svih podataka o dokumentuApstrakt:
To improve safety and efficacy of conventional chemotherapeutics, it is important to target
cancer cells more selectively. Potential strategies could arise from differences in iron
metabolism between healthy and cancer cells, based on cancer cells high demands for iron.
Their, so-called, “iron addiction” sets a foundation for new therapeutic approach. In this
study, the cytotoxic effect of three diiron carbonyl complexes with a bridging thiocarbyne
ligand was evaluated on different human cancer cell lines (HCT116 colorectal carcinoma,
MCF-7 breast cancer and A2780 ovarian cancer), as well as on human embryonic lung
fibroblasts (MRC-5), which were used for selectivity assessment. The most potent
compound (FETPY) decreased viability of all cancer cell lines in dose-dependent manner,
while A2780 cells emerged as the most sensitive. Therefore, they were selected for further
investigation. On the other hand, the effect of FETPY on lung fibroblasts viability was
remarkably less potent, showing its great selectivity towards malignant phenotype.
Additionally, it was shown that intracellular iron concentration was much higher in A2780
than in MRC-5 cells after treatment with FETPY. Viability decrease of A2780 cells was a
consequence of cell death – ferroptosis, caused by iron-dependent lipid peroxidation and
membrane damage. Oxidative stress that caused ferroptosis evolved from intensive
production of nitric oxide and superoxide anion. Controversially, it was followed with
scavenging of hydrogen peroxide and peroxynitrite. Treatment with FETPY also caused
significant decrease of A2780 cells division rate. Overall, these results indicate that the
considered diiron derivatives show great potential for further investigation in cancer
treatment.
Finansiranje / projekti:
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200007 (Univerzitet u Beogradu, Institut za biološka istraživanja 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
U:
- Spasojević I, editor. Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia. Belgrade: Faculty of Chemistry; 2023. p. 68.