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Fialova 2022 Biomed Pharmacother

From Bioblast
Publications in the MiPMap
Fialova JL, Hönigova K, Raudenska M, Miksatkova L, Zobalova R, Navratil J, Šmigová J, Moturu TR, Vicar T, Balvan J, Vesela K, Abramenko N, Kejik Z, Kaplanek R, Gumulec J, Rosel D, Martasek P, Brábek J, Jakubek M, Neuzil J, Masarik M (2022) Pentamethinium salts suppress key metastatic processes by regulating mitochondrial function and inhibiting dihydroorotate dehydrogenase respiration.

» Biomed Pharmacother 154:113582. PMID: 36055111 Open Access

Fialova Jindriska Leischner, Hoenigova Katerina, Raudenska Martina, Miksatkova Lucie, Zobalova Renata, Navratil Jiri, Smigova Jana, Moturu Taraka Ramji, Vicar Tomas, Balvan Jan, Vesela Katerina, Abramenko Nikita, Kejik Zdenek, Kaplanek Robert, Gumulec Jaromir, Rosel Daniel, Martasek Pavel, Brabek Jan, Jakubek Milan, Neuzil Jiri, Masarik Michal (2022) Biomed Pharmacother

Abstract: 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. Keywords: Dihydroorotate dehydrogenase, Metastasis, Migration, Mitochondria, Pentamethinium salts Bioblast editor: Plangger M O2k-Network Lab: CZ Prague Neuzil J

Labels: MiParea: Respiration, Pharmacology;toxicology  Pathology: Cancer 

Organism: Human  Tissue;cell: Endothelial;epithelial;mesothelial cell  Preparation: Permeabilized cells 

Coupling state: OXPHOS 

HRR: Oxygraph-2k