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Toxicity evaluation of synthetic glucocorticoids against breast cancer cell lines MDA-MB-231, MCF-7 and human embryonic kidney HEK293

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Abstract

In this study, we conducted a comprehensive assessment of the cytotoxicity of three glucocorticoids, namely Hydrocortisone, Dexamethasone, and Methylprednisolone, using three different human cell lines: MDA-MB-231, MCF-7 (both adenocarcinoma cell lines), and HEK293 (kidney epithelial cell line). At lower concentrations exceeding 50 µM, we did not observe any significant toxic effects of these glucocorticoids. However, when exposed to higher concentrations, Hydrocortisone exhibited dose-dependent cytotoxic effects on all three cell lines, with calculated IC50 values of 12 ± 0.6 mM for HEK293, 2.11 ± 0.05 mM for MDA-MB-231, and 2.73 ± 0.128 mM for MCF-7 cells after 48 h of exposure. Notably, Hydrocortisone, at its respective IC50 concentrations, demonstrated an inhibitory effect on the proliferation of the cancer cell lines, as evidenced by a substantial reduction in BrdU absorbance in a dose-dependent manner, coupled with a markedly reduced rate of colony formation in treated cells. Furthermore, Hydrocortisone exhibited remarkable anti-migratory properties in MDA-MB-231 and MCF-7 cells, and it induced cell cycle arrest in the SubG1 phase in MDA-MB-231 cells. In addition to these effects, Hydrocortisone triggered apoptosis in both cancer cell types, leading to observable morphological changes. This apoptotic response was characterized by a significant increase in the activity of caspase-3, which was time-dependent. Additionally, Hydrocortisone downregulated the expression of anti-apoptotic Bcl-2 proteins. In summary, our findings underscore the safety of clinical doses in terms of cell toxicity meanwhile increased concentration were showing an anti-proliferative potential of Hydrocortisone, particularly against adenocarcinoma breast cancer cell lines.

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The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Laboratory of Molecular and Cellular Screening Processes, Centre of Biotechnology of Sfax, University of Sfax, Sidi Mansour Road Km 6, BP 1177, 3018, Sfax, Tunisia

    Dhouha Msalbi, Fatma Jellali, Jihene Elloumi-Mseddi, Bochra Hakim, Emna Sahli & Sami Aifa

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  1. Dhouha Msalbi
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  2. Fatma Jellali
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  3. Jihene Elloumi-Mseddi
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  4. Bochra Hakim
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by DM, FJ, JE-M, BH, ES and SA. The first draft of the manuscript was written by DM and SA. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Dhouha Msalbi.

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Msalbi, D., Jellali, F., Elloumi-Mseddi, J. et al. Toxicity evaluation of synthetic glucocorticoids against breast cancer cell lines MDA-MB-231, MCF-7 and human embryonic kidney HEK293. Med Oncol 40, 309 (2023). https://doi.org/10.1007/s12032-023-02189-1

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