Aнтитуморски потенцијал бинуклеарних једињења гвожђа са изоцијанидним лигандом
Antitumor potential of diiron compounds with isocyanide ligands
2023
Authors:
Mihajlović, EkatarinaJelača, Sanja
Biancalana, Lorenzo
Chiaverini, Lorenzo
Mijatović, Sanja
Zacchini, Stefano
Marchetti, Fabio
Maksimović-Ivanić, Danijela
Contributors
Arsenijević, NebojšaDocument Type:
Conference object (Published version)
,
© 2023 by the Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine, Kragujevac, Serbia
Metadata
Show full item recordAbstract:
Metal-based drugs have been used as cancer therapeutics for decades. Unfortunately, their efficacy usually comes with significant toxicity and there is a constant need for the development of drugs with improved safety profile. Iron is an important element with tightly regulated metabolism and plays crucial role in many physiological processes in the body, like growth and development, which is particularly important for cancer cells. Since they have increased iron demands compared to healthy cells, it is expected that they could be more susceptible to treatment with iron compounds than healthy cells. In the present study, the cytotoxic effect of diiron compounds with isocyanide ligands (Xyl-NC, XylNC+DMAP, Ind-NC) was investigated on human cancer cell lines: A2780 ovarian cancer, MCF-7 breast cancer, and HCT116 colorectal carcinoma in vitro. Treatment with experimental compounds decreased the viability of all cancer cell lines, while A2780 was selected for further investigation as the most sensitive one. It was shown that treatment of A2780 cells with diiron compounds with isocyanide ligands caused ferroptosis, cell death induced by iron-dependent lipid peroxidation. Surprisingly, ferroptosis was accompanied by the scavenging of radicals causing oxidative and nitrosative stress - hydrogen peroxide and peroxynitrite. Additionally, all 3 compounds induced autophagy in A2780 cells. Co-treatment with the autophagy inhibitor 3-methyl adenine further decreased cell viability, suggesting that detected autophagy had cytoprotective role. Furthermore, treatment with investigated compounds significantly inhibited the proliferation of A2780 cells. Results obtained in this study indicate that diiron compounds with isocyanide ligands could become promising agents for cancer treatment and therefore, require additional attention and further biological assessment.
improved safety profile. Iron is an important element with tightly regulated metabolism and plays crucial
role in many physiological processes in the body, like growth and development, which is particularly
important for cancer cells. Since they have increased iron demands compared to healthy cells, it is expected
that they could be more susceptible to treatment with iron compounds than healthy cells. In the
present study, the cytotoxic effect of diiron compounds with isocyanide ligands (Xyl-NC, XylNC+DMAP,
Ind-NC) was investigated on human cancer cell lines: A2780 ovarian cancer, MCF-7 breast cancer, and
HCT116 colorectal carcinoma in vitro. Treatment with experimental compounds decreased the viability
of all cancer cell lines, while A2780 was selected for further investigation as the most sensitive one. It was
shown that treatment of A2780 cells with diiron compounds with isocyanide ligands caused ferroptosis,
cell death induced by iron-dependent lipid peroxidation. Surprisingly, ferroptosis was accompanied by
the scavenging of radicals causing oxidative and nitrosative stress - hydrogen peroxide and peroxynitrite.
Additionally, all 3 compounds induced autophagy in A2780 cells. Co-treatment with the autophagy
inhibitor 3-methyl adenine further decreased cell viability, suggesting that detected autophagy had cytoprotective role. Furthermore, treatment with investigated compounds significantly inhibited the proliferation of A2780 cells. Results obtained in this study indicate that diiron compounds with isocyanide
ligands could become promising agents for cancer treatment and therefore, require additional attention
and further biological assessment.
Keywords:
ovarian cancer; iron compounds; ferroptosis; cytoprotective autophagyFunding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
In:
- Arsenijević N, editor. Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina. Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine; 2023. p. 32-3.