Triparanol suppresses human tumor growth in vitro and in vivo

Biochem Biophys Res Commun. 2012 Aug 31;425(3):613-8. doi: 10.1016/j.bbrc.2012.07.136. Epub 2012 Aug 1.

Abstract

Despite the improved contemporary multidisciplinary regimens treating cancer, majority of cancer patients still suffer from adverse effects and relapse, therefore posing a significant challenge to uncover more efficacious molecular therapeutics targeting signaling pathways central to tumorigenesis. Here, our study have demonstrated that Triparanol, a cholesterol synthesis inhibitor, can block proliferation and induce apoptosis in multiple human cancer cells including lung, breast, liver, pancreatic, prostate cancer and melanoma cells, and growth inhibition can be rescued by exogenous addition of cholesterol. Remarkably, we have proved Triparanol can significantly repress Hedgehog pathway signaling in these human cancer cells. Furthermore, study in a mouse xenograft model of human lung cancer has validated that Triparanol can impede tumor growth in vivo. We have therefore uncovered Triparanol as potential new cancer therapeutic in treating multiple types of human cancers with deregulated Hedgehog signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Female
  • Hedgehog Proteins / antagonists & inhibitors*
  • Humans
  • Hypolipidemic Agents / chemistry
  • Hypolipidemic Agents / pharmacology
  • Hypolipidemic Agents / therapeutic use*
  • Mice
  • Mice, Nude
  • Neoplasms / drug therapy*
  • Triparanol / chemistry
  • Triparanol / pharmacology
  • Triparanol / therapeutic use*
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Hedgehog Proteins
  • Hypolipidemic Agents
  • Triparanol