Anti-androgen-independent prostate cancer effects of ginsenoside metabolites in vitro: mechanism and possible structure-activity relationship investigation

Arch Pharm Res. 2009 Jan;32(1):49-57. doi: 10.1007/s12272-009-1117-1. Epub 2009 Jan 29.

Abstract

Treatment of androgen-independent prostate cancer (AIPC) remains unsatisfactory. In our present experiment, natural occurring ginsenosides (NOGs) and intestinal bacterial metabolites (IBMs) were employed to investigate their anti-AIPC cell growth activity using PC-3 cells. Our results showed that the IBMs exerted more portent anti-AIPC activity than NOGs, by decreasing survival rate, inhibiting proliferation, inducing apoptosis, and leading to cell cycle arrest in AIPC PC-3 cells. The increase of LogP and decrease of C-6 steric hindrance, which were caused by deglycosylation by intestinal bacteria, may be the reason for the higher anti-AIPC activity of IBMs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgen Antagonists / pharmacology
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Bacteria / metabolism
  • Biotransformation
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Cyclin A / metabolism
  • Cyclin D1 / metabolism
  • Dose-Response Relationship, Drug
  • Drug Resistance, Neoplasm
  • Ginsenosides / chemistry
  • Ginsenosides / metabolism
  • Ginsenosides / pharmacology*
  • Glycosylation
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Intestines / microbiology
  • Male
  • Mitochondria / drug effects
  • Mitochondria / pathology
  • Molecular Structure
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Structure-Activity Relationship

Substances

  • Androgen Antagonists
  • Antineoplastic Agents
  • CCND1 protein, human
  • Cyclin A
  • Ginsenosides
  • Cyclin D1