Spironolactone Induces Apoptotic Cell Death in Human Glioblastoma U87-MG Cancer Cells

IF 0.4 Q4 ONCOLOGY

International Journal of Cancer Management Pub Date : 2022-10-16 DOI:10.5812/ijcm-128738

Zeinabsadat Mohammadi, Mohammad Mostakhdem Hashemi, Marie Saghaeian Jazi

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引用次数: 0

Abstract

Background: Spironolactone is a conventional drug widely in use for the treatment of heart failure and hypertension patients. On the other side recent studies have reported spironolactone can prevent growth and drug resistance in cancer stem cells (CSCs), by inhibiting DNA double-strand break (DSB) repair; suggesting its potential application in cancer therapy. Objectives: Our study aimed at assessing the potential cytotoxicity of spironolactone in human U87-MG glioblastoma cells. Methods: different concentrations of spironolactone (0 - 50 μM) for 48 and 72 h were used for treatment. Cell viability assay was carried out by the 4, 5-dimethylthiazole-2-yl, 2, 5-diphenyl tetrazolium (MTT) method. Apoptosis was evaluated using annexin V/PI staining and flow cytometry and colorimetric measurement of caspase 8 and 9 activity. Results: our findings showed a significant dose-dependent cytotoxic effect of spironolactone with maximum effect in 30 μM (P-value < 0.05). Spironolactone can induce approximately 20% apoptotic cell death in U87-MG cancer cells which were mainly related to early apoptotic cells. Indeed, the activity of caspase 8 and 9 was significantly elevated in spironolactone-treated cells compared to mock control. Conclusions: Findings showed the cytotoxic effect of spironolactone in U87-MG glioblastoma cancer cells in a mechanism dependent on apoptosis cell death induction. Our findings suggest the potential application of spironolactone in the treatment of glioblastoma in vitro.

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螺内酯诱导人胶质瘤U87-MG癌细胞凋亡细胞死亡

背景:螺内酯是一种广泛用于治疗心力衰竭和高血压的常规药物。另一方面，最近的研究报道螺内酯可以通过抑制DNA双链断裂(DSB)修复来阻止癌症干细胞(CSCs)的生长和耐药;提示其在癌症治疗中的潜在应用。目的:本研究旨在评估螺内酯对人U87-MG胶质母细胞瘤细胞的潜在细胞毒性。方法:用不同浓度的螺内酯(0 ~ 50 μM)处理48、72 h。细胞活力测定采用4,5 -二甲基噻唑-2-基，2,5 -二苯四唑(MTT)法。采用膜联蛋白V/PI染色、流式细胞术和caspase 8、9活性比色法检测细胞凋亡。结果:螺内酯具有明显的剂量依赖性细胞毒作用，在30 μM时效果最大(p值< 0.05)。螺内酯可诱导U87-MG癌细胞约20%的凋亡细胞死亡，主要与早期凋亡细胞有关。事实上，与模拟对照相比，在螺内酯处理的细胞中，caspase 8和9的活性显著升高。结论:研究结果表明螺内酯对U87-MG胶质母细胞瘤癌细胞的细胞毒作用机制依赖于诱导凋亡细胞死亡。我们的发现提示了螺内酯在体外治疗胶质母细胞瘤中的潜在应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Cancer Management ONCOLOGY-

CiteScore

1.10

自引率

0.00%

发文量

期刊介绍： International Journal of Cancer Management (IJCM) publishes peer-reviewed original studies and reviews on cancer etiology, epidemiology and risk factors, novel approach to cancer management including prevention, diagnosis, surgery, radiotherapy, medical oncology, and issues regarding cancer survivorship and palliative care. The scope spans the spectrum of cancer research from the laboratory to the clinic, with special emphasis on translational cancer research that bridge the laboratory and clinic. We also consider original case reports that expand clinical cancer knowledge and convey important best practice messages.