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Article

Cytostatic Effect of a Novel Mitochondria-Targeted Pyrroline Nitroxide in Human Breast Cancer Lines

1
Department of Biochemistry and Medical Chemistry, University of Pecs Medical School, 7624 Pecs, Hungary
2
Institute of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Pecs, 7624 Pecs, Hungary
3
Szentagothai Research Centre, University of Pecs, 7624 Pecs, Hungary
4
HAS-UP Nuclear-Mitochondrial Interactions Research Group, 1245 Budapest, Hungary
*
Author to whom correspondence should be addressed.
Academic Editor: Vladimir Titorenko
Int. J. Mol. Sci. 2021, 22(16), 9016; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22169016
Received: 30 June 2021 / Revised: 30 July 2021 / Accepted: 17 August 2021 / Published: 20 August 2021
(This article belongs to the Special Issue New Drugs for Breast Cancer Treatment)
Mitochondria have emerged as a prospective target to overcome drug resistance that limits triple-negative breast cancer therapy. A novel mitochondria-targeted compound, HO-5114, demonstrated higher cytotoxicity against human breast cancer lines than its component-derivative, Mito-CP. In this study, we examined HO-5114′s anti-neoplastic properties and its effects on mitochondrial functions in MCF7 and MDA-MB-231 human breast cancer cell lines. At a 10 µM concentration and within 24 h, the drug markedly reduced viability and elevated apoptosis in both cell lines. After seven days of exposure, even at a 75 nM concentration, HO-5114 significantly reduced invasive growth and colony formation. A 4 h treatment with 2.5 µM HO-5114 caused a massive loss of mitochondrial membrane potential, a decrease in basal and maximal respiration, and mitochondrial and glycolytic ATP production. However, reactive oxygen species production was only moderately elevated by HO-5114, indicating that oxidative stress did not significantly contribute to the drug’s anti-neoplastic effect. These data indicate that HO-5114 may have potential for use in the therapy of triple-negative breast cancer; however, the in vivo toxicity and anti-neoplastic effectiveness of the drug must be determined to confirm its potential. View Full-Text
Keywords: MDA-MB-231; MCF7; mitochondrial membrane potential; mitochondrial energy metabolism; reactive oxygen species; invasive growth; Mito-CP MDA-MB-231; MCF7; mitochondrial membrane potential; mitochondrial energy metabolism; reactive oxygen species; invasive growth; Mito-CP
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MDPI and ACS Style

Andreidesz, K.; Szabo, A.; Kovacs, D.; Koszegi, B.; Bagone Vantus, V.; Vamos, E.; Isbera, M.; Kalai, T.; Bognar, Z.; Kovacs, K.; Gallyas, F. Cytostatic Effect of a Novel Mitochondria-Targeted Pyrroline Nitroxide in Human Breast Cancer Lines. Int. J. Mol. Sci. 2021, 22, 9016. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22169016

AMA Style

Andreidesz K, Szabo A, Kovacs D, Koszegi B, Bagone Vantus V, Vamos E, Isbera M, Kalai T, Bognar Z, Kovacs K, Gallyas F. Cytostatic Effect of a Novel Mitochondria-Targeted Pyrroline Nitroxide in Human Breast Cancer Lines. International Journal of Molecular Sciences. 2021; 22(16):9016. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22169016

Chicago/Turabian Style

Andreidesz, Kitti, Aliz Szabo, Dominika Kovacs, Balazs Koszegi, Viola Bagone Vantus, Eszter Vamos, Mostafa Isbera, Tamas Kalai, Zita Bognar, Krisztina Kovacs, and Ferenc Gallyas. 2021. "Cytostatic Effect of a Novel Mitochondria-Targeted Pyrroline Nitroxide in Human Breast Cancer Lines" International Journal of Molecular Sciences 22, no. 16: 9016. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22169016

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