Agrimonolide inhibits glycolysis in ovarian cancer cells by regulating HIF1A

IF 1.5 4区医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis Pub Date : 2024-07-01 DOI:10.1016/j.mrfmmm.2024.111884

Yi Yang, Huimin Wang, Qiong Wei, Chun Li

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Abstract

Background

Ovarian cancer is one of the most common tumors affecting females, significantly disrupting their quality of life. Agrimonolide, an extract derived from Agrimony (Agrimonia pilosa Ledeb.), has been shown to exert various regulatory effects on several diseases. Notably, recent studies indicate that Agrimonolide may attenuate the progression of ovarian cancer. However, the detailed regulatory mechanisms of Agrimonolide in this context require further investigation.

Purpose

To determine the significance of HIF1A as a key target in ovarian cancer and its potential underlying signaling pathway.

Methods

Cell viability and proliferation were assessed using CCK-8 and colony formation assays. Glucose uptake and lactate production were measured using commercial kits, and the extracellular acidification rate (ECAR) was evaluated. Protein expression levels were analyzed through western blotting.

Results

Our network pharmacology analysis identified HIF1A as a crucial target and signaling pathway in ovarian cancer. Furthermore, treatment with Agrimonolide (20 μM and 40 μM) inhibited the growth of ovarian cancer cells. Agrimonolide also reduced glycolytic activity in these cells. Additionally, Agrimonolide treatment led to decreased expression levels of HIF1A, HK2, and LDHA in ovarian cancer cells. Rescue assays revealed that glucose uptake and lactate production were diminished following Agrimonolide treatment; however, these effects were reversed upon overexpression of HIF1A.

Conclusion

This study showed that Agrimonolide can suppress glycolysis in ovarian cancer cells by modulating HIF1A, supporting Agrimonolide as a promising therapeutic agent for ovarian cancer treatment.

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嘧菌酯通过调节 HIF1A 抑制卵巢癌细胞中的糖酵解作用

背景卵巢癌是女性最常见的肿瘤之一，严重影响女性的生活质量。从枸杞（Agrimonia pilosa Ledeb.）中提取的枸杞内酯（Agrimonolide）已被证明对多种疾病具有不同的调节作用。值得注意的是，最近的研究表明，Agrimonolide 可减轻卵巢癌的进展。目的确定 HIF1A 作为卵巢癌关键靶点的重要性及其潜在的信号通路。方法使用 CCK-8 和集落形成试验评估细胞活力和增殖。使用商业试剂盒测量葡萄糖摄取量和乳酸生成量，并评估细胞外酸化率（ECAR）。结果我们的网络药理学分析确定 HIF1A 是卵巢癌的关键靶点和信号通路。此外，用阿格列莫内酯（20 μM 和 40 μM）处理可抑制卵巢癌细胞的生长。阿格列莫内酯还能降低这些细胞的糖酵解活性。此外，Agrimonolide 还能降低卵巢癌细胞中 HIF1A、HK2 和 LDHA 的表达水平。这项研究表明，阿格莫内酯可通过调节 HIF1A 来抑制卵巢癌细胞中的糖酵解，从而支持阿格莫内酯成为一种治疗卵巢癌的有效药物。

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

Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis 生物-毒理学

CiteScore

4.90

自引率

0.00%

发文量

审稿时长

51 days

期刊介绍： Mutation Research (MR) provides a platform for publishing all aspects of DNA mutations and epimutations, from basic evolutionary aspects to translational applications in genetic and epigenetic diagnostics and therapy. Mutations are defined as all possible alterations in DNA sequence and sequence organization, from point mutations to genome structural variation, chromosomal aberrations and aneuploidy. Epimutations are defined as alterations in the epigenome, i.e., changes in DNA methylation, histone modification and small regulatory RNAs. MR publishes articles in the following areas: Of special interest are basic mechanisms through which DNA damage and mutations impact development and differentiation, stem cell biology and cell fate in general, including various forms of cell death and cellular senescence. The study of genome instability in human molecular epidemiology and in relation to complex phenotypes, such as human disease, is considered a growing area of importance. Mechanisms of (epi)mutation induction, for example, during DNA repair, replication or recombination; novel methods of (epi)mutation detection, with a focus on ultra-high-throughput sequencing. Landscape of somatic mutations and epimutations in cancer and aging. Role of de novo mutations in human disease and aging; mutations in population genomics. Interactions between mutations and epimutations. The role of epimutations in chromatin structure and function. Mitochondrial DNA mutations and their consequences in terms of human disease and aging. Novel ways to generate mutations and epimutations in cell lines and animal models.