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

Prostate. 2008 Jun 1;68(8):809-19. doi: 10.1002/pros.20742.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / 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
  • Ginsenosides / therapeutic use*
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / radiotherapy
  • Xenograft Model Antitumor Assays

Substances

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