Guggulsterone induces apoptosis in colon cancer cells and inhibits tumor growth in murine colorectal cancer xenografts

Cancer Lett. 2009 Jun 28;279(1):93-100. doi: 10.1016/j.canlet.2009.01.026. Epub 2009 Feb 18.

Abstract

The plant sterol guggulsterone has recently been shown to have anti-tumorigenic potential. This study was designed to investigate the anti-tumor efficacy of guggulsterone and to elucidate its molecular mechanisms in colon cancer. Guggulsterone significantly increased apoptosis in HT-29 cells by activating caspases-3 and -8. Furthermore, guggulsterone decreased cIAP-1, cIAP-2, and Bcl-2 levels and increased the levels of truncated Bid, Fas, p-JNK, and p-c-Jun. The size of HT-29 xenograft tumors in guggulsterone-treated mice was significantly smaller than of the size of tumors in control mice. The present study suggests a potential therapeutic use for this compound in the treatment of colorectal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • BH3 Interacting Domain Death Agonist Protein / metabolism
  • Baculoviral IAP Repeat-Containing 3 Protein
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Cell Proliferation / drug effects*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Dose-Response Relationship, Drug
  • Enzyme Activation
  • HT29 Cells
  • Humans
  • Inhibitor of Apoptosis Proteins / metabolism
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Male
  • Mice
  • Mice, Nude
  • Phosphorylation
  • Pregnenediones / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Proto-Oncogene Proteins c-jun / metabolism
  • Time Factors
  • Ubiquitin-Protein Ligases
  • Xenograft Model Antitumor Assays
  • fas Receptor / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • BH3 Interacting Domain Death Agonist Protein
  • BID protein, human
  • FAS protein, human
  • Inhibitor of Apoptosis Proteins
  • Pregnenediones
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-jun
  • fas Receptor
  • pregna-4,17-diene-3,16-dione
  • BIRC3 protein, human
  • Baculoviral IAP Repeat-Containing 3 Protein
  • Ubiquitin-Protein Ligases
  • JNK Mitogen-Activated Protein Kinases
  • CASP3 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 9