Effects of 17β-estradiol and estrogen receptor subtype-specific agonists on Jurkat E6.1 T-cell leukemia cells

IF 2.6 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro Pub Date : 2025-03-18 DOI:10.1016/j.tiv.2025.106057

Rahul S. Nair , Mantavya N. Patel , Thangamani Kannan , Shaili Gour , Murali M. Hariharan , Vijayarengamani Prasanna , Anupriya Thirumalai , Ramanathan Chockalingam , Ramasamy Vasantharekha , Srinivasan ThyagaRajan , Hannah P. Priyanka

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引用次数: 0

Abstract

Background

Estrogen signaling plays a crucial role in immune regulation and cancer metabolism, yet its impact on T-cell leukemia remains unclear. In hematological malignancies, estrogen receptor (ER) activation may influence metabolic shifts that affect cell survival and proliferation. This study investigates the in vitro effects of 17β-estradiol and estrogen receptor subtype-specific agonists on Jurkat E6.1 T-cell leukemia cells.

Purpose

To assess how estrogen signaling influences metabolic reprogramming, inflammatory response, and survival pathways in Jurkat E6.1 cells through receptor-dependent and independent mechanisms.

Methods

Jurkat E6.1 cells incubated with different concentrations of 17β-estradiol (10⁻¹² M, 10⁻¹⁰ M, 10⁻⁸ M) or ER-α agonist 4,4′,4″-(4-Propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (10⁻¹⁰ M, 10⁻⁸ M, 10⁻⁶ M) or ER-β agonist diarylproprionitrile (10⁻¹⁰ M, 10⁻⁸ M, 10⁻⁶ M) with and without non-specific antagonist ICI 182,780 (10⁻⁶ M). The metabolic enzyme activities of hexokinase, pyruvate kinase, and citrate synthase were measured in cell pellets, while supernatants were analyzed for IL-6 and nitric oxide (NO) production. Additionally, PI3K/Akt pathway activation was assessed by measuring p-Akt/Total Akt expression.

Results

A shift from glycolysis to oxidative phosphorylation was observed on treatment with 17β-estradiol with significant decline in hexokinase activity and a concomitant increase in activities of pyruvate kinase and citrate synthase.

Conclusion

17β-estradiol mediates its effects on Jurkat E6.1 cells in vitro through receptor-subtype dependent and independent mechanisms involving metabolic enzymes (hexokinase, pyruvate kinase, citrate synthase), cytokines (IL-6), nitric oxide, and signaling molecules (p-Akt).

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来源期刊

Toxicology in Vitro 医学-毒理学

CiteScore

6.50

自引率

3.10%

发文量

181

审稿时长

65 days

期刊介绍： Toxicology in Vitro publishes original research papers and reviews on the application and use of in vitro systems for assessing or predicting the toxic effects of chemicals and elucidating their mechanisms of action. These in vitro techniques include utilizing cell or tissue cultures, isolated cells, tissue slices, subcellular fractions, transgenic cell cultures, and cells from transgenic organisms, as well as in silico modelling. The Journal will focus on investigations that involve the development and validation of new in vitro methods, e.g. for prediction of toxic effects based on traditional and in silico modelling; on the use of methods in high-throughput toxicology and pharmacology; elucidation of mechanisms of toxic action; the application of genomics, transcriptomics and proteomics in toxicology, as well as on comparative studies that characterise the relationship between in vitro and in vivo findings. The Journal strongly encourages the submission of manuscripts that focus on the development of in vitro methods, their practical applications and regulatory use (e.g. in the areas of food components cosmetics, pharmaceuticals, pesticides, and industrial chemicals). Toxicology in Vitro discourages papers that record reporting on toxicological effects from materials, such as plant extracts or herbal medicines, that have not been chemically characterized.