Počet záznamů: 1
Targeting Mitochondrial Iron Metabolism Suppresses Tumor Growth and Metastasis by Inducing Mitochondrial Dysfunction and Mitophagy
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SYSNO ASEP 0548987 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Targeting Mitochondrial Iron Metabolism Suppresses Tumor Growth and Metastasis by Inducing Mitochondrial Dysfunction and Mitophagy Tvůrce(i) Sandoval-Acuna, Cristian (BTO-N)
Torrealba, Natalia (BTO-N)
Tomkova, Veronika (BTO-N)
Jadhav, Sukanya B. (BTO-N)
Blažková, Kristýna (BTO-N)
Merta, L. (CZ)
Lettlová, Sandra (BTO-N)
Adamcová, Miroslava Kari (UMG-J)
Rosel, D. (CZ)
Brabek, J. (CZ)
Neužil, Jiří (BTO-N) RID
Štursa, Jan (BTO-N)
Werner, Lukáš (BTO-N)
Truksa, Jaroslav (BTO-N) RID, ORCIDCelkový počet autorů 14 Zdroj.dok. Cancer Research. - : American Association for Cancer Research - ISSN 0008-5472
Roč. 81, č. 9 (2021), s. 2289-2303Poč.str. 15 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova sulfur cluster ; cancer ; biogenesis ; breast ; cells Vědní obor RIV FD - Onkologie a hematologie Obor OECD Oncology Vědní obor RIV – spolupráce Ústav molekulární genetiky - Onkologie a hematologie CEP GA16-12816S GA ČR - Grantová agentura ČR GA18-13103S GA ČR - Grantová agentura ČR GC17-01192J GA ČR - Grantová agentura ČR GA18-10832S GA ČR - Grantová agentura ČR Způsob publikování Omezený přístup Institucionální podpora BTO-N - RVO:86652036 ; UMG-J - RVO:68378050 UT WOS 000647325600005 EID SCOPUS 85105525103 DOI 10.1158/0008-5472.CAN-20-1628 Anotace Deferoxamine (DFO) represents a widely used iron chelator for the treatment of iron overload. Here we describe the use of mitochondrially targeted deferoxamine (mitoDFO) as a novel approach to preferentially target cancer cells. The agent showed marked cytostatic, cytotoxic, and migrastatic properties in vitro, and it significantly suppressed tumor growth and metastasis in vivo. The underlying molecular mechanisms included (I) impairment of [Fe-S] cluster/heme biogenesis, leading to destabilization and loss of activity of [Fe-S] cluster/heme containing enzymes, (II) inhibition of mitochondrial respiration leading to mitochondrial ROS production, resulting in dysfunctional mitochondria with markedly reduced supercomplexes, and (III) fragmentation of the mitochondrial network and induction of mitophagy. Mitochondrial targeting of DFO represents a way to deprive cancer cells of biologically active iron, which is incompatible with their proliferation and invasion, without disrupting systemic iron metabolism. Our findings highlight the importance of mitochondrial iron metabolism for cancer cells and demonstrate repurposing deferoxamine into an effective anti-cancer drug via mitochondrial targeting. Pracoviště Biotechnologický ústav Kontakt Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Rok sběru 2022 Elektronická adresa https://cancerres.aacrjournals.org/content/81/9/2289
Počet záznamů: 1