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

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.
Authors	Wei Wang, Jiang-Jiang Qin, Xin Li, Guanyu Tao, Qiang Wang, Xuming Wu, Jianwei Zhou, Xiaolin Zi, Ruiwen Zhang
Journal	Carcinogenesis (Carcinogenesis) Vol. 39 Issue 8 Pg. 1026-1036 (07 30 2018) ISSN: 1460-2180 [Electronic] England
PMID	29762656 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Copyright	© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].
Chemical References	25-methoxydammarane-3,12,20-triol Cell Cycle Proteins MDM4 protein, human Mdm4 protein, mouse Nuclear Proteins Proto-Oncogene Proteins Triterpenes MDM2 protein, human Mdm2 protein, mouse Proto-Oncogene Proteins c-mdm2
Topics	Animals Cell Cycle Proteins Cell Line, Tumor Disease Models, Animal Drug Screening Assays, Antitumor Humans Male Mice Mice, Transgenic Nuclear Proteins (metabolism) Prostatic Neoplasms (drug therapy, genetics, pathology) Protein Binding (drug effects) Proteolysis (drug effects) Proto-Oncogene Proteins (metabolism) Proto-Oncogene Proteins c-mdm2 (antagonists & inhibitors, metabolism) RING Finger Domains (drug effects) Triterpenes (pharmacology, therapeutic use)

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