RHOA and mDia1 Promotes Apoptosis of Breast Cancer Cells Via a High Dose of Doxorubicin Treatment.

Autor:	Bober P; Department of Medical and Clinical Biophysics, Faculty of Medicine, University of P.J. Šafárik in Košice, Trieda SNP1, 04011 Košice, Slovakia., Alexovič M; Department of Medical and Clinical Biophysics, Faculty of Medicine, University of P.J. Šafárik in Košice, Trieda SNP1, 04011 Košice, Slovakia., Tomková Z; Department of Medical and Clinical Biophysics, Faculty of Medicine, University of P.J. Šafárik in Košice, Trieda SNP1, 04011 Košice, Slovakia., Kilík R; 1st Department of Surgery, Faculty of Medicine, University of P.J. Šafárik in Košice, Trieda SNP1, 04011 Košice, Slovakia., Sabo J; Department of Medical and Clinical Biophysics, Faculty of Medicine, University of P.J. Šafárik in Košice, Trieda SNP1, 04011 Košice, Slovakia.
Jazyk:	angličtina
Zdroj:	Open life sciences [Open Life Sci] 2019 Dec 31; Vol. 14, pp. 619-627. Date of Electronic Publication: 2019 Dec 31 (Print Publication: 2019).
DOI:	10.1515/biol-2019-0070
Abstrakt:	Background: Transforming RhoA proteins (RHOA) and their downstream Diaphanous homolog 1 proteins (DIAPH1) or mDia1 participate in the regulation of actin cytoskeleton which plays critical role in cells, i.e., morphologic changes and apoptosis. Methodology: To determine the cell viability the real time cell analysis (RTCA) and flow cytometry were used. To perform proteomic analysis, the label-free quantitative method and post-translation modification by the nano-HPLC and ESI-MS ion trap mass analyser were used. Results: The results of the cell viability showed an increase of dead cells (around 30 %) in MCF-7/DOX-1 (i.e., 1μM of doxorubicin was added to MCF-7/WT breast cancer cell line) compared to MCF-7/WT (control) after 24 h doxorubicin (DOX) treatment. The signalling pathway of the Regulation of actin cytoskeleton (p<0.0026) was determined, where RHOA and mDia1 proteins were up-regulated. Also, post-translational modification analysis of these proteins in MCF-7/DOX-1 cells revealed dysregulation of the actin cytoskeleton, specifically the collapse of actin stress fibbers due to phosphorylation of RHOA at serine 188 and mDia1 at serine 22, resulting in their deactivation and cell apoptosis. Conclusion: These results pointed to an assumed role of DOX to dysregulation of actin cytoskeleton and cell death. Competing Interests: Conflict of interest: Authors state no conflict of interest. (© 2019 Peter Bober et al. published by De Gruyter.)
Databáze:	MEDLINE
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