Cytostatic Effect of a Novel Mitochondria-Targeted Pyrroline Nitroxide in Human Breast Cancer Lines |
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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. |
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Affiliation: | 1.Department of Biochemistry and Medical Chemistry, University of Pecs Medical School, 7624 Pecs, Hungary; (K.A.); (A.S.); (D.K.); (B.K.); (V.B.V.); (E.V.); (Z.B.); (K.K.);2.Institute of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Pecs, 7624 Pecs, Hungary; (M.I.); (T.K.);3.Szentagothai Research Centre, University of Pecs, 7624 Pecs, Hungary;4.HAS-UP Nuclear-Mitochondrial Interactions Research Group, 1245 Budapest, Hungary |
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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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Keywords: | MDA-MB-231 MCF7 mitochondrial membrane potential mitochondrial energy metabolism reactive oxygen species invasive growth Mito-CP |
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