Targeting Mitochondrial Iron Metabolism Suppresses Tumor Growth
and Metastasis by Inducing Mitochondrial Dysfunction and
Mitophagy

J 2021

Targeting Mitochondrial Iron Metabolism Suppresses Tumor Growth and Metastasis by Inducing Mitochondrial Dysfunction and Mitophagy

SANDOVAL-ACUNA, Cristian; Natalia TORREALBA; Veronika TOMKOVA; Sukanya B JADHAV; Kristyna BLAZKOVA et al.

Základní údaje

Originální název

Targeting Mitochondrial Iron Metabolism Suppresses Tumor Growth and Metastasis by Inducing Mitochondrial Dysfunction and Mitophagy

Autoři

Vydání

Cancer Research, PHILADELPHIA, AMER ASSOC CANCER RESEARCH, 2021, 0008-5472

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 13.312

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:90043/21:00139235

Organizační jednotka

CIISB

Klíčová slova anglicky

SULFUR CLUSTER; CANCER; BIOGENESIS; BREAST; CELLS; DEFERASIROX; EXPRESSION; CHELATORS; STRATEGY; ISCU

Štítky

ne MU, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 29. 3. 2025 09:16, Mgr. Eva Dubská

Anotace

V originále

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.

Návaznosti

90043, velká výzkumná infrastruktura

Název: CIISB

Citovat

SANDOVAL-ACUNA, Cristian; Natalia TORREALBA; Veronika TOMKOVA; Sukanya B JADHAV; Kristyna BLAZKOVA; Ladislav MERTA; Sandra LETTLOVA; Miroslava K ADAMCOVA; Daniel ROSEL; Jan BRABEK; Jiri NEUZIL; Jan STURSA; Lukas WERNER a Jaroslav TRUKSA. Targeting Mitochondrial Iron Metabolism Suppresses Tumor Growth and Metastasis by Inducing Mitochondrial Dysfunction and Mitophagy. Cancer Research. PHILADELPHIA: AMER ASSOC CANCER RESEARCH, 2021, roč. 81, č. 9, s. 2289-2303. ISSN 0008-5472. Dostupné z: https://doi.org/10.1158/0008-5472.CAN-20-1628.

@article{2487405,
   author = {SandovalandAcuna, Cristian and Torrealba, Natalia and Tomkova, Veronika and Jadhav, Sukanya B and Blazkova, Kristyna and Merta, Ladislav and Lettlova, Sandra and Adamcova, Miroslava K and Rosel, Daniel and Brabek, Jan and Neuzil, Jiri and Stursa, Jan and Werner, Lukas and Truksa, Jaroslav},
   article_location = {PHILADELPHIA},
   article_number = {9},
   doi = {https://doi.org/10.1158/0008-5472.CAN-20-1628},
   keywords = {SULFUR CLUSTER; CANCER; BIOGENESIS; BREAST; CELLS; DEFERASIROX; EXPRESSION; CHELATORS; STRATEGY; ISCU},
   language = {eng},
   issn = {0008-5472},
   journal = {Cancer Research},
   title = {Targeting Mitochondrial Iron Metabolism Suppresses Tumor Growth and Metastasis by Inducing Mitochondrial Dysfunction and Mitophagy},
   url = {https://aacrjournals.org/cancerres/article-abstract/81/9/2289/670615/Targeting-Mitochondrial-Iron-Metabolism-Suppresses?redirectedFrom=fulltext},
   volume = {81},
   year = {2021}
}

TY  - JOUR
ID  - 2487405
AU  - Sandoval-Acuna, Cristian - Torrealba, Natalia - Tomkova, Veronika - Jadhav, Sukanya B - Blazkova, Kristyna - Merta, Ladislav - Lettlova, Sandra - Adamcova, Miroslava K - Rosel, Daniel - Brabek, Jan - Neuzil, Jiri - Stursa, Jan - Werner, Lukas - Truksa, Jaroslav
PY  - 2021
TI  - Targeting Mitochondrial Iron Metabolism Suppresses Tumor Growth and Metastasis by Inducing Mitochondrial Dysfunction and Mitophagy
JF  - Cancer Research
VL  - 81
IS  - 9
SP  - 2289-2303
EP  - 2289-2303
PB  - AMER ASSOC CANCER RESEARCH
SN  - 00085472
KW  - SULFUR CLUSTER
KW  - CANCER
KW  - BIOGENESIS
KW  - BREAST
KW  - CELLS
KW  - DEFERASIROX
KW  - EXPRESSION
KW  - CHELATORS
KW  - STRATEGY
KW  - ISCU
UR  - https://aacrjournals.org/cancerres/article-abstract/81/9/2289/670615/Targeting-Mitochondrial-Iron-Metabolism-Suppresses?redirectedFrom=fulltext
N2  - 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.
ER  -

SANDOVAL-ACUNA, Cristian; Natalia TORREALBA; Veronika TOMKOVA; Sukanya B JADHAV; Kristyna BLAZKOVA; Ladislav MERTA; Sandra LETTLOVA; Miroslava K ADAMCOVA; Daniel ROSEL; Jan BRABEK; Jiri NEUZIL; Jan STURSA; Lukas WERNER a Jaroslav TRUKSA. Targeting Mitochondrial Iron Metabolism Suppresses Tumor Growth and Metastasis by Inducing Mitochondrial Dysfunction and Mitophagy. \textit{Cancer Research}. PHILADELPHIA: AMER ASSOC CANCER RESEARCH, 2021, roč.~81, č.~9, s.~2289-2303. ISSN~0008-5472. Dostupné z: https://doi.org/10.1158/0008-5472.CAN-20-1628.

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