Interaction between moxifloxacin and Mcl-1 and MITF proteins: the effect on growth inhibition and apoptosis in MDA-MB-231 human triple-negative breast cancer cells
Background Microphthalmia-associated transcription factor (MITF) activates the expression of genes involved in cellular proliferation, DNA replication, and repair, whereas Mcl-1 is a member of the Bcl-2 family of proteins that promotes cell survival by preventing apoptosis. The objective of the present study was to verify whether the interaction between moxifloxacin (MFLX), one of the fluoroquinolones, and MITF/Mcl-1 protein, could affect the viability, proliferation, and apoptosis in human breast cancer using both in silico and in vitro models. Methods Molecular docking analysis (in silico), fluorescence image cytometry, and Western blot (in vitro) techniques were applied to assess the contribution of MITF and Mcl-1 proteins in the MFLX-induced anti-proliferative and pro-apoptotic effects on the MDA-MB-231 breast cancer cells. Results We indicated the ability of MFLX to form complexes with MITF and Mcl-1 as well as the drug’s capacity to affect the expression of the tested proteins. We also showed that MFLX decreased the viability and proliferation of MDA-MB-231 cells and induced apoptosis via the intrinsic death pathway. Moreover, the analysis of the cell cycle progression revealed that MFLX caused a block in the S and G2/M phases. Conclusions We demonstrated for the first time that the observed effects of MFLX on MDA-MB-231 breast cancer cells (growth inhibition and apoptosis induction) could be related to the drug’s ability to interact with MITF and Mcl-1 proteins. Furthermore, the presented results suggest that MITF and Mcl-1 proteins could be considered as the target in the therapy of breast cancer. Graphical abstract.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:74 |
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| Enthalten in: |
Pharmacological reports - 74(2022), 5 vom: 01. Sept., Seite 1025-1040 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Beberok, Artur [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| Themen: |
Breast cancer |
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| Anmerkungen: |
© The Author(s) 2022 |
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| doi: |
10.1007/s43440-022-00407-7 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Background Microphthalmia-associated transcription factor (MITF) activates the expression of genes involved in cellular proliferation, DNA replication, and repair, whereas Mcl-1 is a member of the Bcl-2 family of proteins that promotes cell survival by preventing apoptosis. The objective of the present study was to verify whether the interaction between moxifloxacin (MFLX), one of the fluoroquinolones, and MITF/Mcl-1 protein, could affect the viability, proliferation, and apoptosis in human breast cancer using both in silico and in vitro models. Methods Molecular docking analysis (in silico), fluorescence image cytometry, and Western blot (in vitro) techniques were applied to assess the contribution of MITF and Mcl-1 proteins in the MFLX-induced anti-proliferative and pro-apoptotic effects on the MDA-MB-231 breast cancer cells. Results We indicated the ability of MFLX to form complexes with MITF and Mcl-1 as well as the drug’s capacity to affect the expression of the tested proteins. We also showed that MFLX decreased the viability and proliferation of MDA-MB-231 cells and induced apoptosis via the intrinsic death pathway. Moreover, the analysis of the cell cycle progression revealed that MFLX caused a block in the S and G2/M phases. Conclusions We demonstrated for the first time that the observed effects of MFLX on MDA-MB-231 breast cancer cells (growth inhibition and apoptosis induction) could be related to the drug’s ability to interact with MITF and Mcl-1 proteins. Furthermore, the presented results suggest that MITF and Mcl-1 proteins could be considered as the target in the therapy of breast cancer. Graphical abstract | ||
| 650 | 4 | |a Breast cancer |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Moxifloxacin |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a In silico analysis |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Cellular homeostasis |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Rok, Jakub |4 aut | |
| 700 | 1 | |a Rzepka, Zuzanna |4 aut | |
| 700 | 1 | |a Marciniec, Krzysztof |4 aut | |
| 700 | 1 | |a Boryczka, Stanisław |4 aut | |
| 700 | 1 | |a Wrześniok, Dorota |4 aut | |
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