Cytostatic Effect of a Novel Mitochondria-Targeted Pyrroline Nitroxide in Human Breast Cancer Lines.
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| Abstract |
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.
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| Authors | Kitti Andreidesz, Aliz Szabo, Dominika Kovacs, Balazs Koszegi, Viola Bagone Vantus, Eszter Vamos, Mostafa Isbera, Tamas Kalai, Zita Bognar, Krisztina Kovacs, Ferenc Gallyas Jr |
| Journal | International journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 16 (Aug 20 2021) ISSN: 1422-0067 [Electronic] Switzerland |
| PMID | 34445722 (Publication Type: Journal Article) |
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