Experimental therapy of prostate cancer with novel natural product anti-cancer ginsenosides.

Abstract

BACKGROUND:

Ginseng and its components exert various biological effects, including antioxidant, anti-carcinogenic, anti-mutagenic, and anti-tumor activity, and recent research has focused on their value in human cancer prevention and treatment. We recently isolated 25-hydroxyprotopanaxadiol (25-OH-PPD) and 25-hydroxyprotopanaxatriol (25-OH-PPT) from Panax ginseng and evaluated their anti-cancer activity in vitro.

METHODS:

We compared the effects of the two compounds on human prostate cancer LNCaP and PC3 cells in vitro and in a mouse PC3 xenograft tumor model. We also accomplished a preliminary determination of the mechanisms of action of the compounds.

RESULTS:

25-OH-PPD, but not 25-OH-PPT, inhibited prostate cancer cell growth and proliferation, induced apoptosis, and led to arrest in the G1 phase of the cell cycle. In nude mice bearing PC3 xenograft tumors, 25-OH-PPD inhibited tumor growth in a dose-dependent manner and could be safely combined with chemotherapeutic agents (taxotere and gemcitabine) and radiation therapy to improve the anti-tumor effects. Further, in both PC3 and LNCaP cell lines, 25-OH-PPD increased expression of p21, p27, and Bax, induced PARP cleavage and activated caspases. The compound also reduced expression of MDM2, E2F1, Bcl2, cdk2/4/6, and cyclin D1, which correlated with the cell cycle arrest in G1 and the decrease in proliferation. Moreover, 25-OH-PPD demonstrated low toxicity to non-cancer cells and no observable host toxicity in animals either alone or in combination with conventional therapies.

CONCLUSIONS:

The newly identified ginsenoside 25-OH-PPD may have potential as a novel prostate cancer therapeutic agent.

• Authors: Wei Wang, Elizabeth R Rayburn, Miao Hao, Yuqing Zhao, Donald L Hill, Ruiwen Zhang, Hui Wang
• Journal: The Prostate (Prostate) Vol. 68 Issue 8 Pg. 809-19 (Jun 01 2008) ISSN: 0270-4137 [Print] United States
• PMID: 18324646 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: (c) 2008 Wiley-Liss, Inc.

Chemical References

• 25-hydroxyprotopanaxadiol
• 25-hydroxyprotopanaxatriol
• Antineoplastic Agents, Phytogenic
• Ginsenosides

Topics

• Animals
• Antineoplastic Agents, Phytogenic (chemistry, therapeutic use)
• Apoptosis
• Cell Line, Transformed
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Combined Modality Therapy
• Fibroblasts (drug effects)
• G1 Phase (drug effects)
• Ginsenosides (chemistry, therapeutic use)
• Humans
• Male
• Mice
• Mice, Nude
• Prostatic Neoplasms (drug therapy, pathology, radiotherapy)
• Xenograft Model Antitumor Assays