Planta Med 2016; 82(S 01): S1-S381
DOI: 10.1055/s-0036-1596955
Abstracts
Georg Thieme Verlag KG Stuttgart · New York

A novel ginsenoside 20(S)-protopanaxadiol inhibits growth of castration-resistant human prostate cancer

Authors

  • M Ben-Eltriki

    1   The Vancouver Prostate Centre at Vancouver General Hospital, 2660 Oak Street, Vancouver, BC, V6 H 3Z6, Canada
    2   Department of Experimental Medicine, Faculty of Medicine, University of British Columbia, Vancouver, B.C, Canada

  • M Hassona

    1   The Vancouver Prostate Centre at Vancouver General Hospital, 2660 Oak Street, Vancouver, BC, V6 H 3Z6, Canada

  • G Meckling

    1   The Vancouver Prostate Centre at Vancouver General Hospital, 2660 Oak Street, Vancouver, BC, V6 H 3Z6, Canada

  • L Fazli

    1   The Vancouver Prostate Centre at Vancouver General Hospital, 2660 Oak Street, Vancouver, BC, V6 H 3Z6, Canada
    3   Department of Urologic Sciences, Faculty of Medicine, University of British Columbia, Vancouver, B.C, Canada

  • S Deb

    4   Department of Biopharmaceutical Sciences, College of Pharmacy at Roosevelt University, Schaumburg, IL, USA 60173

  • ES Tomlinson Guns

    1   The Vancouver Prostate Centre at Vancouver General Hospital, 2660 Oak Street, Vancouver, BC, V6 H 3Z6, Canada
    3   Department of Urologic Sciences, Faculty of Medicine, University of British Columbia, Vancouver, B.C, Canada
Further Information

Publication History

Publication Date:
14 December 2016 (online)

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Prostate cancer (PCa) is the leading cause of cancer related deaths in men. To date, the therapeutic options for advanced PCa are limited. Ginseng is one the commonly ingested natural product supplements in the Western countries and a widely used medicinal herb in complementary and alternative medicine worldwide. We have shown that 20(S)-protopanaxadiol (aPPD), a naturally derived ginsenoside aglycone from ginseng, has anti-cancer activity in vitro and in the preclinical mice prostate cancer models [1 – 3]. Here we explored the potential effects of aPPD against metastatic castration-resistant human prostate cancer mouse xenografts. In vivo efficacy studies in C4 – 2 xenograft mice PCa model and immunohistochemical (IHC) analyses were performed. The animals bearing C4 – 2 tumors were castrated and then treated daily with 70 mg/kg body weight aPPD by oral gavage along with vehicle controls for 6 weeks. Tumor growth was determined by measuring tumor volume changes, the harvested C4 – 2 tumors were IHC stained with Ki-67 expression as markers of proliferation and cleaved caspase-3 to establish apoptotic indices. aPPD caused established C4 – 2 tumors to shrink by 53% and serum prostate-specific antigen trends were decreased by 25% with aPPD than control. Further, the IHC analyzing xenografted tumors showed that tumor cell proliferation rate (measured by Ki-67 positive cells) was significantly lower for aPPD, this was associated with elevated levels of cleaved caspase-3 expression, compared to mice treated with vehicle alone. Together, we demonstrate that aPPD potently inhibits PCa cell growth in vivo and concurrently induce apoptosis. These preclinical results support testing of aPPD in a clinical setting in advanced human PCa patients.

Acknowledgements: Shanghai Innovative Research Centre of Traditional Chinese Medicine is acknowledged for generously providing the purified 20(S) protopanaxadiol.

Keywords: 20(S)-protopanaxadiol ginsenoside, treatment, castration resistant prostate cancer.

References:

[1] Ben-Eltriki M, Deb S, Adomat H, Tomlinson Guns ES. Calcitriol and 20(S)-protopanaxadiol synergistically inhibit growth and induce apoptosis in human prostate cancer cells. J Steroid Biochem Mol Biol 2016; 158: 207 – 219.

[2] Musende AG, Eberding A, Wood CA, Adomat H, Fazli L, Hurtado-Coll A, Jia W, Bally MB, Tomlinson Guns ES. A novel oral dosage formulation of the ginsenoside aglycone protopanaxadiol exhibits therapeutic activity against a hormone-insensitive model of prostate cancer. Anticancer Drugs 2012; 23: 543 – 552.

[3] Musende AG, Eberding A, Jia W, Ramsay E, Bally MB, Guns ET. Rh2 or its aglycone aPPD in combination with docetaxel for treatment of prostate cancer. Prostate 2010; 70: 1437 – 1447.


No conflict of interest has been declared by the author(s).