Prevention of prostate cancer by natural product MDM2 inhibitor GS25: in vitro and in vivo activities and molecular mechanisms

Carcinogenesis
Wei WangRuiwen Zhang

Abstract

Prostate cancer remains a major health problem in the USA and worldwide. There is an urgent need to develop novel approaches to preventing primary and metastatic prostate cancer. We have identified 25-OCH3-protopanaxadiol (GS25), the most active ginsenoside that has been identified so far; it has potent activity against human cancers, including prostate cancer. However, it has not been proven if GS25 could be a safe and effective agent for cancer prevention. In this study, we used the TRAMP model and clearly demonstrated that GS25 inhibited prostate tumorigenesis and metastasis with minimal host toxicity. Mechanistically, GS25 directly bound to the RING domain of MDM2, disrupted MDM2-MDMX binding and induced MDM2 protein degradation, resulting in strong inhibition of prostate cancer cell growth and metastasis, independent of p53 and androgen receptor status. In conclusion, our in vitro and in vivo data support the potential use of GS25 in prevention of primary and metastatic prostate cancer.

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Citations

Oct 7, 2019·Medicinal Research Reviews·Wei WangRuiwen Zhang
Aug 28, 2020·Frontiers in Oncology·De-Hua YuJiang-Jiang Qin
Apr 24, 2020·Frontiers in Pharmacology·Jia ZhangJiang-Jiang Qin
Apr 18, 2020·Frontiers in Cell and Developmental Biology·Si-Min QiJiang-Jiang Qin
Jul 23, 2020·Frontiers in Pharmacology·Wen-Kai YuJiang-Jiang Qin
Feb 12, 2021·Frontiers in Pharmacology·Liuqing YangQin Zhang
Nov 13, 2020·Frontiers in Pharmacology·Junqing HuangJia-Xu Chen
May 15, 2021·Journal of Evidence-based Medicine·Dehua YuJiangjiang Qin

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