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Pentamethinium salts suppress key metastatic processes by regulating mitochondrial function and inhibiting dihydroorotate dehydrogenase respiration

JL. Fialova, K. Hönigova, M. Raudenska, L. Miksatkova, R. Zobalova, J. Navratil, J. Šmigová, TR. Moturu, T. Vicar, J. Balvan, K. Vesela, N. Abramenko, Z. Kejik, R. Kaplanek, J. Gumulec, D. Rosel, P. Martasek, J. Brábek, M. Jakubek, J. Neuzil, M. Masarik

. 2022 ; 154 (-) : 113582. [pub] 20220830

Jazyk angličtina Země Francie

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc22024235

Mitochondria generate energy and building blocks required for cellular growth and function. The notion that mitochondria are not involved in the cancer growth has been challenged in recent years together with the emerging idea of mitochondria as a promising therapeutic target for oncologic diseases. Pentamethinium salts, cyan dyes with positively charged nitrogen on the benzothiazole or indole part of the molecule, were originally designed as mitochondrial probes. In this study, we show that pentamethinium salts have a strong effect on mitochondria, suppressing cancer cell proliferation and migration. This is likely linked to the strong inhibitory effect of the salts on dihydroorotate dehydrogenase (DHODH)-dependent respiration that has a key role in the de novo pyrimidine synthesis pathway. We also show that pentamethinium salts cause oxidative stress, redistribution of mitochondria, and a decrease in mitochondria mass. In conclusion, pentamethinium salts present novel anti-cancer agents worthy of further studies.

Citace poskytuje Crossref.org

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$a Fialova, Jindriska Leischner $u Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-625 00 Brno, Czech Republic; Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-625 00 Brno, Czech Republic
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$a Pentamethinium salts suppress key metastatic processes by regulating mitochondrial function and inhibiting dihydroorotate dehydrogenase respiration / $c JL. Fialova, K. Hönigova, M. Raudenska, L. Miksatkova, R. Zobalova, J. Navratil, J. Šmigová, TR. Moturu, T. Vicar, J. Balvan, K. Vesela, N. Abramenko, Z. Kejik, R. Kaplanek, J. Gumulec, D. Rosel, P. Martasek, J. Brábek, M. Jakubek, J. Neuzil, M. Masarik
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$a Mitochondria generate energy and building blocks required for cellular growth and function. The notion that mitochondria are not involved in the cancer growth has been challenged in recent years together with the emerging idea of mitochondria as a promising therapeutic target for oncologic diseases. Pentamethinium salts, cyan dyes with positively charged nitrogen on the benzothiazole or indole part of the molecule, were originally designed as mitochondrial probes. In this study, we show that pentamethinium salts have a strong effect on mitochondria, suppressing cancer cell proliferation and migration. This is likely linked to the strong inhibitory effect of the salts on dihydroorotate dehydrogenase (DHODH)-dependent respiration that has a key role in the de novo pyrimidine synthesis pathway. We also show that pentamethinium salts cause oxidative stress, redistribution of mitochondria, and a decrease in mitochondria mass. In conclusion, pentamethinium salts present novel anti-cancer agents worthy of further studies.
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$a Hönigova, Katerina $u Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-625 00 Brno, Czech Republic; Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-625 00 Brno, Czech Republic
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$a Raudenska, Martina $u Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-625 00 Brno, Czech Republic; Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-625 00 Brno, Czech Republic; Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00, Brno, Czech Republic
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$a Miksatkova, Lucie $u BIOCEV, First Faculty of Medicine, Charles University, Prumyslova 595, CZ-252 50 Vestec, Czech Republic; Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 455, 120 00 Prague, Czech Republic
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$a Zobalová, Renata $u Institute of Biotechnology, Czech Academy of Sciences, Prumyslova 595, CZ-252 50 Vestec, Czech Republic $7 xx0310352
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$a Navrátil, Jiří $u Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-625 00 Brno, Czech Republic; Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-625 00 Brno, Czech Republic $7 xx0266342
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$a Šmigová, Jana $u Department of Cell Biology, Charles University, Viničná 7, 128 44 Prague, Czech Republic; Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University (BIOCEV), Průmyslová 595, 252 42 Vestec u Prahy, Czech Republic
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$a Moturu, Taraka Ramji $u Crop Production and Biostimulation Laboratory, Interfacultary School of Bioengineers, Université libre de Bruxelles, Belgium
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$a Vicar, Tomas $u Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-625 00 Brno, Czech Republic; Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-625 00 Brno, Czech Republic
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$a Balvan, Jan $u Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-625 00 Brno, Czech Republic; Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-625 00 Brno, Czech Republic
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$a Vesela, Katerina $u BIOCEV, First Faculty of Medicine, Charles University, Prumyslova 595, CZ-252 50 Vestec, Czech Republic; Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 455, 120 00 Prague, Czech Republic
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$a Abramenko, Nikita $u BIOCEV, First Faculty of Medicine, Charles University, Prumyslova 595, CZ-252 50 Vestec, Czech Republic; Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 455, 120 00 Prague, Czech Republic
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$a Kejik, Zdenek $u BIOCEV, First Faculty of Medicine, Charles University, Prumyslova 595, CZ-252 50 Vestec, Czech Republic; Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 455, 120 00 Prague, Czech Republic
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$a Kaplanek, Robert $u BIOCEV, First Faculty of Medicine, Charles University, Prumyslova 595, CZ-252 50 Vestec, Czech Republic; Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 455, 120 00 Prague, Czech Republic
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$a Gumulec, Jaromir $u Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-625 00 Brno, Czech Republic; Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-625 00 Brno, Czech Republic
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$a Rosel, Daniel $u Department of Cell Biology, Charles University, Viničná 7, 128 44 Prague, Czech Republic; Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University (BIOCEV), Průmyslová 595, 252 42 Vestec u Prahy, Czech Republic
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$a Martasek, Pavel $u Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 455, 120 00 Prague, Czech Republic
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$a Brábek, Jan $u Department of Cell Biology, Charles University, Viničná 7, 128 44 Prague, Czech Republic; Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University (BIOCEV), Průmyslová 595, 252 42 Vestec u Prahy, Czech Republic
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$a Jakubek, Milan $u BIOCEV, First Faculty of Medicine, Charles University, Prumyslova 595, CZ-252 50 Vestec, Czech Republic; Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 455, 120 00 Prague, Czech Republic. Electronic address: milan.jakubek@lf1.cuni.cz
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$a Neuzil, Jiri $u Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 455, 120 00 Prague, Czech Republic; Institute of Biotechnology, Czech Academy of Sciences, Prumyslova 595, CZ-252 50 Vestec, Czech Republic; School of Pharmacy and Medical Science, Griffith University, Parklands Avenue, Southport 4222 QLD, Australia; Faculty of Science, Charles University, Vinicna 7, Prague 128 44, Czech Republic. Electronic address: jiri.neuzil@ibt.cas.cz
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$a Masarik, Michal $u Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-625 00 Brno, Czech Republic; Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-625 00 Brno, Czech Republic; BIOCEV, First Faculty of Medicine, Charles University, Prumyslova 595, CZ-252 50 Vestec, Czech Republic. Electronic address: masarik@med.muni.cz
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