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

Wei Li ¹, Hao Liu ², Jie Zheng ³

⁰School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.

Journal of Ethnopharmacology +

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November 27, 2024

View abstract on PubMed

Summary

Chaihu-Shugan-San (CSS) may treat stress-induced prostate cancer metastasis. Its active ingredient, kaempferol, inhibits the GR/PER1 pathway, increasing alpha2M secretion and reducing cancer cell migration.

Area Of Science

Oncology
Pharmacology
Traditional Chinese Medicine

Background

Prostate cancer patients undergoing androgen deprivation therapy often experience depression.
Chaihu-Shugan-San (CSS) shows potential in preventing prostate cancer metastasis exacerbated by chronic unpredictable mild stress (CUMS).
The active components and molecular mechanisms of CSS in this context are not fully understood.

Purpose Of The Study

To investigate the molecular targets and mechanisms of CSS in treating emotional stress-induced prostate cancer metastasis.
To identify key active ingredients in CSS responsible for its therapeutic effects.
To elucidate the role of the GR/PER1 pathway and lipid metabolism in stress-aggravated prostate cancer.

Main Methods

Investigated the effects of CSS and its active ingredients on prostate cancer cell migration and metastasis in a CUMS model.
Utilized bone marrow-derived macrophages (BMDMs) to study the GR/PER1 pathway and alpha2M secretion.
Examined the impact of kaempferol on GR nuclear translocation and the GR/PER1 pathway in Per1-overexpressed BMDMs.

Main Results

Stress promotes GR nuclear translocation and PER1 transcription, altering lipid metabolism and decreasing alpha2M secretion in BMDMs.
CSS treatment improved prostate cancer metastasis in CUMS-induced mice.
Kaempferol, a CSS component, significantly enhanced alpha2M secretion and inhibited prostate cancer cell migration, while also suppressing GR nuclear translocation and the GR/PER1 pathway.

Conclusions

Emotional stress exacerbates prostate cancer growth and metastasis via the GR/PER1 pathway and altered lipid metabolism.
Suppression of the GR/PER1 pathway increases alpha2M secretion in BMDMs, inhibiting prostate cancer cell metastasis.
Kaempferol is a key active ingredient in CSS that targets the GR/PER1 pathway to mitigate stress-induced prostate cancer progression.

Keywords:

Chaihu-shugan-san Emotional stress GR/PER1 Prostate cancer ɑ2M

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