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

Carcinogenesis 2018 May 12. Epub 2018 May 12.

Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, Texas, USA.

Prostate cancer remains a major health problem in the US 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 the present 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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http://dx.doi.org/10.1093/carcin/bgy063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067121PMC
May 2018
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