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.
Med Oncol. 2023 Sep 29;40(11):309. doi: 10.1007/s12032-023-02189-1.
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.
在这项研究中，我们使用三种不同的人类细胞系：MDA-MB-231、MCF-7（均为腺癌细胞系）和 HEK293（肾上皮细胞系），对三种糖皮质激素（Hydrocortisone、Dexamethasone 和 Methylprednisolone）的细胞毒性进行了全面评估。在超过 50µM 的较低浓度下，我们没有观察到这些糖皮质激素有任何明显的毒性作用。然而，当暴露于更高浓度时，Hydrocortisone 对所有三种细胞系均表现出剂量依赖性的细胞毒性作用，在 48 小时暴露后，HEK293 的 IC50 值为 12±0.6mM，MDA-MB-231 为 2.11±0.05mM，MCF-7 为 2.73±0.128mM。值得注意的是，Hydrocortisone 在其各自的 IC50 浓度下，对癌细胞系的增殖表现出抑制作用，这表现在 BrdU 吸光度呈剂量依赖性显著降低，同时处理细胞中的集落形成率明显降低。此外，Hydrocortisone 在 MDA-MB-231 和 MCF-7 细胞中表现出显著的抗迁移特性，并在 MDA-MB-231 细胞中诱导细胞周期停滞在 SubG1 期。除了这些作用外，Hydrocortisone 还在两种癌细胞类型中引发细胞凋亡，导致可观察到的形态变化。这种凋亡反应的特征是 caspase-3 的活性显著增加，呈时间依赖性。此外，Hydrocortisone 下调了抗凋亡 Bcl-2 蛋白的表达。总之，我们的研究结果强调了临床剂量在细胞毒性方面的安全性，同时增加浓度显示了 Hydrocortisone 的抗增殖潜力，特别是针对腺癌乳腺癌细胞系。
