Reynoutria multiflora (Thunb.) Moldenke and its ingredient suppress lethal prostate cancer growth by inducing CDC25B-CDK1 mediated cell cycle arrest.

Autor: Zhou Q; The Center of Cancer Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China., Wu F; The Center of Cancer Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, China., Chen Y; The Center of Cancer Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China., Fu J; The Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China., Zhou L; Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, China., Xu Y; Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China., He F; The Center of Cancer Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: fhe@shutcm.edu.cn., Gong Z; The Center of Cancer Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: zhangbingong@126.com., Yuan F; The Center of Cancer Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Department of Urology and Andrology, Gongli Hospital, Shanghai 200135, China. Electronic address: yuanfuwen@pku.edu.cn.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2024 Nov; Vol. 152, pp. 107731. Date of Electronic Publication: 2024 Aug 21.
DOI: 10.1016/j.bioorg.2024.107731
Abstrakt: Background: Reynoutria multiflora (Thunb.) Moldenke (Polygonum multiflorum Thunb, PM) is a medicinal plant that was an element of traditional Chinese medicine (TCM) for centuries as a treatment for a wide range of conditions. Recent studies reported that PM suppressed prostate cancer growth in an AR-dependent manner. However, its role and mechanism in the treatment of advanced prostate cancer remain to be explored. This study aims to explore the anti-tumor role and potential mechanism of PM on prostate cancer.
Methods: Cell viability, colony formation, fluorescence-activated cell sorting (FACS), and wound-healing assays were conducted to evaluate the tumor suppression effect of PM on lethal prostate cancer models in vitro. A xenograft mice model was established to detect the impact of PM on tumor growth and evaluate its biosafety in vivo. Integrative network pharmacology, RNA-seq, and bioinformatics were applied to determine the mechanisms of PM in prostate cancer. Molecular docking, cellular thermal shift assay (CETSA), CRISPR-Cas13, RT-qPCR, and WB were collaboratively employed to identify the potential anti-tumor ingredient derived from PM and its corresponding targets.
Results: PM significantly suppressed the growth of prostate cancer and sensitized prostate cancer to AR antagonists. Mechanistically, PM induced G2/M-phase cell-cycle arrest by modulating the phosphorylation of CDK1. Additionally, polygalacic acid derived from PM and its structural analog suppress prostate cancer growth by targeting CDC25B, a master regulator of the cell cycle that governs CDK1 phosphorylation.
Conclusion: PM and its ingredient polygalacic acid suppress lethal prostate cancer growth by regulating the CDC25B-CDK1 axis to induce cell cycle arrest.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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