The Center of Cancer Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
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.
Bioorg Chem. 2024 Nov;152:107731. doi: 10.1016/j.bioorg.2024.107731. Epub 2024 Aug 21.
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.
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.
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.
PM and its ingredient polygalacic acid suppress lethal prostate cancer growth by regulating the CDC25B-CDK1 axis to induce cell cycle arrest.
多花野蔷薇（Thunb.）Moldenke（Polygonum multiflorum Thunb，PM）是一种药用植物，几个世纪以来一直是中药（TCM）的一部分，用于治疗多种疾病。最近的研究报告称，PM 以 AR 依赖性方式抑制前列腺癌的生长。然而，其在治疗晚期前列腺癌中的作用和机制仍有待探索。本研究旨在探讨 PM 对前列腺癌的抗肿瘤作用及其潜在机制。
通过细胞活力、集落形成、荧光激活细胞分选（FACS）和划痕愈合实验，评估 PM 对体外致死性前列腺癌模型的肿瘤抑制作用。建立异种移植小鼠模型，检测 PM 对肿瘤生长的影响，并评估其体内生物安全性。综合网络药理学、RNA-seq 和生物信息学用于确定 PM 在前列腺癌中的作用机制。分子对接、细胞热转移分析（CETSA）、CRISPR-Cas13、RT-qPCR 和 WB 协同用于鉴定源自 PM 的潜在抗肿瘤成分及其相应的靶标。
PM 显著抑制前列腺癌的生长，并使前列腺癌对 AR 拮抗剂敏感。在机制上，PM 通过调节 CDK1 的磷酸化诱导 G2/M 期细胞周期停滞。此外，PM 来源的原儿茶酸及其结构类似物通过靶向细胞周期的主调控因子 CDC25B 抑制前列腺癌的生长，CDC25B 调控 CDK1 的磷酸化。
PM 及其成分原儿茶酸通过调节 CDC25B-CDK1 轴抑制致死性前列腺癌的生长，诱导细胞周期停滞。
