27-Hydroxycholesterol in cancer development and drug resistance.

IF 5.6 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-05-22 DOI:10.1080/14756366.2025.2507670

Yaxin Hou, Zhiguang Fu, Chenhui Wang, Paulina Kucharzewska, Yuan Guo, Sihe Zhang

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引用次数: 0

Abstract

27-Hydroxycholesterol (27HC), a cholesterol metabolite, functions both as a selective oestrogen receptor (ER) modulator and a ligand for liver X receptors (LXRs). The discovery of 27HC involvement in carcinogenesis has unveiled new research avenues, yet its precise role remains controversial and context-dependent. In this review, we provide an overview of the biosynthesis and metabolism of 27HC and explore its cancer-associated signalling, with a particular focus on ER- and LXR-mediated pathways. Given the tissue-specific dual role of 27HC, we discuss its differential impact across various cancer types. Furthermore, we sort out 27HC-contributed drug resistance mechanisms from the perspectives of drug efflux, cellular proliferation, apoptosis, epithelial-mesenchymal transition (EMT), antioxidant defence, epigenetic modification, and metabolic reprogramming. Finally, we highlight the chemical inhibitors to mitigate 27HC-driven cancer progression and drug resistance. This review offers an updated role of 27HC in cancer biology, setting the stage for future research and the development of targeted therapeutics.

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27-羟基胆固醇在癌症发展和耐药中的作用。

27-羟基胆固醇（27-Hydroxycholesterol, 27HC）是一种胆固醇代谢物，具有选择性雌激素受体（ER）调节剂和肝脏X受体（LXRs）配体的功能。27HC参与致癌作用的发现开辟了新的研究途径，但其确切作用仍然存在争议，并且取决于环境。在这篇综述中，我们概述了27HC的生物合成和代谢，并探讨了其与癌症相关的信号传导，特别关注ER-和lxr介导的途径。鉴于27HC的组织特异性双重作用，我们讨论了它在不同癌症类型中的差异影响。此外，我们从药物外排、细胞增殖、细胞凋亡、上皮-间质转化（EMT）、抗氧化防御、表观遗传修饰和代谢重编程等方面梳理了27hc的耐药机制。最后，我们重点介绍了缓解27hc驱动的癌症进展和耐药的化学抑制剂。本文综述了27HC在癌症生物学中的最新作用，为未来的研究和靶向治疗的发展奠定了基础。

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

Journal of Enzyme Inhibition and Medicinal Chemistry 医学-生化与分子生物学

CiteScore

10.30

自引率

10.70%

发文量

195

审稿时长

4-8 weeks

期刊介绍： Journal of Enzyme Inhibition and Medicinal Chemistry publishes open access research on enzyme inhibitors, inhibitory processes, and agonist/antagonist receptor interactions in the development of medicinal and anti-cancer agents. Journal of Enzyme Inhibition and Medicinal Chemistry aims to provide an international and interdisciplinary platform for the latest findings in enzyme inhibition research. The journal’s focus includes current developments in: Enzymology; Cell biology; Chemical biology; Microbiology; Physiology; Pharmacology leading to drug design; Molecular recognition processes; Distribution and metabolism of biologically active compounds.