RHOA and MDia1 Promotes Apoptosis of Breast Cancer Cells Via a High Dose of Doxorubicin Treatment

Overview

Journal Open Life Sci

Specialty Biology

Date 2021 Apr 5

PMID 33817200

Citations 12

Authors

Peter Bober

Michal Alexovic

Zuzana Tomkova

Robert Kilik

Jan Sabo

Affiliations

Soon will be listed here.

Abstract

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.

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