Thymoquinone suppresses cell growth and induces ferroptosis in renal cell carcinoma by reducing SERPINH1 expression

IF 1.6 4区医学 Q4 CHEMISTRY, MEDICINAL

Letters in Drug Design & Discovery Pub Date : 2025-02-01 DOI:10.1016/j.lddd.2025.100013

Ruiying Luo, Shuang Li, Haohao Wang, Zuyu Zhang, Long Li, Panfeng Shang

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引用次数: 2

Abstract

Thymoquinone (TQ) plays an important role in regulating cell behaviors of renal cell carcinoma (RCC). Ferroptosis is an iron-dependent cell death involving in cancer repression. Herein, the effect of TQ on ferroptosis and its association with serpin family H member 1 (SERPINH1) were investigated. Real-time quantitative PCR and western blot were adopted for mRNA and protein detection. Cell growth was assessed by cell counting kit-8 and colony formation assays. Flow cytometry was performed for apoptosis examination. Transwell assay was used to measure cell migration and invasion. Reactive oxygen species (ROS), glutathione (GSH), and Fe 2+ were determined by the corresponding kits. SERPINH1 was an up-regulated gene in RCC. Silence of SERPINH1 blocked RCC cell growth, migration and invasion but induced apoptosis and ferroptosis. TQ could target SERPINH1 and down-regulated the expression of SERPINH1. TQ suppressed cell viability and facilitated ferroptosis, which was attributed to level inhibition of SERPINH1. These results disclosed that TQ acted on SERPINH1 to down-regulate its expression, consequently hindering cell progression and motivating ferroptosis in RCC. SERPINH1 may be a biological marker in the treatment of TQ for RCC by targeting ferroptosis.

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百里醌通过降低SERPINH1表达抑制肾细胞癌细胞生长并诱导铁下垂

百里醌（TQ）在肾细胞癌（RCC）的细胞行为调控中起重要作用。铁下垂是一种涉及癌症抑制的铁依赖性细胞死亡。本文研究了TQ对铁下垂的影响及其与serpin家族H成员1 （SERPINH1）的关系。采用实时荧光定量PCR和western blot检测mRNA和蛋白。通过细胞计数试剂盒-8和菌落形成试验评估细胞生长情况。流式细胞术检测细胞凋亡。Transwell法检测细胞迁移和侵袭。采用相应试剂盒测定活性氧（ROS）、谷胱甘肽（GSH）、铁离子（fe2 +）含量。SERPINH1基因在RCC中表达上调。沉默SERPINH1可阻断RCC细胞的生长、迁移和侵袭，但可诱导细胞凋亡和铁凋亡。TQ可以靶向SERPINH1，下调SERPINH1的表达。TQ抑制细胞活力，促进铁下垂，这归因于SERPINH1的水平抑制。这些结果表明，TQ作用于SERPINH1下调其表达，从而阻碍细胞进展并促进RCC铁下垂。SERPINH1可能是通过靶向铁下垂治疗RCC TQ的生物学标记物。

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

Letters in Drug Design & Discovery 医学-医药化学

CiteScore

1.80

自引率

10.00%

发文量

245

审稿时长

3 months

期刊介绍： Aims & Scope Letters in Drug Design & Discovery publishes letters, mini-reviews, highlights and guest edited thematic issues in all areas of rational drug design and discovery including medicinal chemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, and structure-activity relationships. The emphasis is on publishing quality papers very rapidly by taking full advantage of latest Internet technology for both submission and review of manuscripts. The online journal is an essential reading to all pharmaceutical scientists involved in research in drug design and discovery.