Kaempferol modulates ɑ2M secretion in bone marrow-derived macrophages by downregulating GR/PER1-mediated lipid metabolism to attenuate the emotional stress-aggravated metastasis of prostate cancer

IF 4.8 2区医学 Q1 CHEMISTRY, MEDICINAL

Journal of ethnopharmacology Pub Date : 2024-11-26 DOI:10.1016/j.jep.2024.119162

Wei Li , Hao Liu , Jie Zheng , Dechao Wang , Zhiying Wang , Min Hong , Yuxin Zhou

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引用次数: 0

Abstract

Ethnopharmacological relevance

Prostate cancer patients often suffer from depression during androgen deprivation therapy. Chaihu-Shugan-San (CSS) can prevent prostate cancer metastasis caused by chronic unpredictable mild stress (CUMS), but its active ingredients and molecular mechanism remain unelucidated.

Aim of study

This study aims to explore the potential targets and molecular mechanisms of CSS in the treatment of emotional stress-aggravated metastasis of prostate cancer.

Results

Stress induces nuclear translocation of GR, initiating the transcription of PER1, which leads to an enhanced lipid metabolism and decreased secretion of α2M in BMDMs. CSS, a classical Traditional Chinese Medicine (TCM) formula for alleviating depression, can improve prostate cancer metastasis caused by CUMS. Of the active ingredients in CSS, kaempferol demonstrated the highest potency for enhancing α2M secretion in BMDMs and inhibiting prostate cancer cell migration. Kaempferol also inhibited nuclear translocation of GR and the GR/PER1 pathway in Per1-overexpressed BMDMs.

Conclusions

These findings reveal that emotional stress-aggravated prostate cancer growth and metastasis rely on the GR/PER1 pathway and lipid metabolism, as the suppression of this pathway ultimately leads to an increase in α2M secretion in BMDMs and inhibition of PC-3 cell metastasis.

Abstract Image

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山奈酚通过下调GR/PER1介导的脂质代谢调节骨髓源性巨噬细胞的ɑ2M分泌，从而减轻情绪压力导致的前列腺癌转移。

民族药理学意义：前列腺癌患者在接受雄激素剥夺治疗期间通常会出现抑郁。柴胡舒筋散（Chanhu-Shugan-San，CSS）可预防慢性不可预知的轻度应激（CUMS）导致的前列腺癌转移，但其有效成分和分子机制仍未阐明：研究目的：本研究旨在探索 CSS 治疗情绪应激加重的前列腺癌转移的潜在靶点和分子机制：结果：应激诱导GR核转位，启动PER1转录，导致BMDMs脂质代谢增强，α2M分泌减少。CSS是一种经典的中医解郁配方，可改善CUMS引起的前列腺癌转移。在 CSS 的有效成分中，山奈酚在增强 BMDMs α2M 分泌和抑制前列腺癌细胞迁移方面的效力最高。山奈酚还能抑制Per1表达的BMDMs中GR的核转位和GR/PER1通路：这些发现揭示了情绪应激导致的前列腺癌生长和转移依赖于GR/PER1通路和脂质代谢，因为抑制该通路最终会导致BMDMs中α2M分泌的增加和PC-3细胞转移的抑制。

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 ethnopharmacology 医学-全科医学与补充医学

CiteScore

10.30

自引率

5.60%

发文量

967

审稿时长

77 days

期刊介绍： The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.