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膳食植物化学物质吲哚 - 3 - 甲醇调节小鼠前列腺组织中的代谢重编程。

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

作者信息

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

机构信息

Department of Pharmaceutics, Ernest Mario School of Pharmacy, The State University of New Jersey, RutgersPiscataway, NJ, 08854, USA.

Graduate Program of Pharmaceutical Sciences, Ernest Mario School of Pharmacy, The State University of New Jersey, RutgersPiscataway, NJ, 08854, USA.

出版信息

Pharm Res. 2025 Feb;42(2):237-247. doi: 10.1007/s11095-025-03820-8. Epub 2025 Feb 4.

DOI:10.1007/s11095-025-03820-8
PMID:39904853
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11880055/
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.

摘要

目的

吲哚 - 3 - 甲醇（I3C）具有多种药理活性，如抗炎、抗菌、抗氧化、抗病毒和抗癌活性。它被广泛认为是多种信号通路的调节剂，特别是那些与细胞周期、细胞生长和分裂、血管生成、细胞凋亡和免疫相关的信号通路。我们探索了基于I3C处理的小鼠前列腺组织中的代谢重编程。

方法

在本研究中，我们利用PTEN基因敲除（KO）诱导的前列腺肿瘤发生小鼠模型，通过代谢重塑来研究I3C的作用机制。10号染色体上缺失的磷酸酶和张力蛋白同源物（PTEN）是一种肿瘤抑制基因，在前列腺癌中经常发现其发生突变或缺失。使用基于液相色谱 - 质谱（LC - MS）的平台进行非靶向代谢组学分析，以研究I3C的PTEN依赖性和非依赖性代谢靶点。

结果

受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

这些途径共同有助于理解I3C对整体健康的有益作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/910f/11880055/20ebab2dae2c/11095_2025_3820_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/910f/11880055/66f0ce38dd47/11095_2025_3820_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/910f/11880055/246cface3831/11095_2025_3820_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/910f/11880055/b73427a12b28/11095_2025_3820_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/910f/11880055/a463399887f1/11095_2025_3820_Fig4a_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/910f/11880055/e5a5b0dafb9e/11095_2025_3820_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/910f/11880055/2ad64b6dd42d/11095_2025_3820_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/910f/11880055/20ebab2dae2c/11095_2025_3820_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/910f/11880055/66f0ce38dd47/11095_2025_3820_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/910f/11880055/246cface3831/11095_2025_3820_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/910f/11880055/b73427a12b28/11095_2025_3820_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/910f/11880055/a463399887f1/11095_2025_3820_Fig4a_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/910f/11880055/e5a5b0dafb9e/11095_2025_3820_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/910f/11880055/2ad64b6dd42d/11095_2025_3820_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/910f/11880055/20ebab2dae2c/11095_2025_3820_Fig7_HTML.jpg

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