Dietary phytochemical indole-3-carbinol regulates metabolic reprogramming in mouse prostate tissue.

IF 4.3 3区医学 Q2 CHEMISTRY, MULTIDISCIPLINARY Pharmaceutical Research Pub Date : 2025-02-01 Epub Date: 2025-02-04 DOI:10.1007/s11095-025-03820-8

Rebecca Mary Peter, Md Shahid Sarwar, Lujing Wang, Pochung Chou, Chao Wang, Yujue Wang, Xiaoyang Su, Ah-Ng Kong

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Abstract

Purpose: Indole-3-carbinol (I3C) is shown to possess multiple pharmacological activities such as anti-inflammatory, antimicrobial, antioxidant, antiviral, and anti-cancer activities. It is widely accepted as modulator of multiple signaling pathways particularly those related to cell cycle, cell growth and division, angiogenesis, apoptosis and immunity. We explored the metabolic reprogramming based on treatment with I3C in mice prostate tissue.

Methods: In this study we utilized Pten knockout (KO)-induced prostate tumorigenesis mouse model to examine mechanism of action of I3C via metabolic rewiring. Phosphatase and tensin homolog deleted on chromosome 10 (Pten), a tumor suppressor gene is frequently found to be mutated or deleted in prostate cancer. Untargeted metabolomics was performed using liquid-chromatography mass-spectrometry (LC-MS) based platform to investigate Pten-dependent and Pten-independent metabolic targets of I3C.

Results: The most impacted pathways by I3C included pyrimidine metabolism, arginine and proline metabolism, porphyrin metabolism, citrate cycle and lipoic acid metabolism.

Conclusion: These pathways taken together help in understanding the overall health beneficial effects of I3C.

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膳食植物化学物吲哚-3-甲醇调节小鼠前列腺组织的代谢重编程。

目的：吲哚-3-甲醇（I3C）具有抗炎、抗菌、抗氧化、抗病毒、抗癌等多种药理活性。它被广泛认为是多种信号通路的调节剂，特别是与细胞周期、细胞生长和分裂、血管生成、细胞凋亡和免疫有关的信号通路。我们探索了基于I3C治疗的小鼠前列腺组织代谢重编程。方法：采用Pten基因敲除（KO）诱导前列腺肿瘤发生小鼠模型，研究I3C通过代谢重布线的作用机制。10号染色体上的磷酸酶和紧张素同源物缺失（Pten）是一种肿瘤抑制基因，在前列腺癌中经常发现突变或缺失。采用液相色谱-质谱（LC-MS）平台进行非靶向代谢组学研究I3C的pten依赖性和pten非依赖性代谢靶点。结果：I3C影响最大的途径包括嘧啶代谢、精氨酸和脯氨酸代谢、卟啉代谢、柠檬酸循环和硫辛酸代谢。结论：这些途径综合起来有助于理解I3C的整体健康益处。

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

Pharmaceutical Research 医学-化学综合

CiteScore

6.60

自引率

5.40%

发文量

276

审稿时长

3.4 months

期刊介绍： Pharmaceutical Research, an official journal of the American Association of Pharmaceutical Scientists, is committed to publishing novel research that is mechanism-based, hypothesis-driven and addresses significant issues in drug discovery, development and regulation. Current areas of interest include, but are not limited to: -(pre)formulation engineering and processing- computational biopharmaceutics- drug delivery and targeting- molecular biopharmaceutics and drug disposition (including cellular and molecular pharmacology)- pharmacokinetics, pharmacodynamics and pharmacogenetics. Research may involve nonclinical and clinical studies, and utilize both in vitro and in vivo approaches. Studies on small drug molecules, pharmaceutical solid materials (including biomaterials, polymers and nanoparticles) biotechnology products (including genes, peptides, proteins and vaccines), and genetically engineered cells are welcome.