Antimetastatic activity and low systemic toxicity of tetradecyl gallate in a preclinical melanoma mouse model

Invest New Drugs. 2012 Jun;30(3):870-9. doi: 10.1007/s10637-010-9628-7. Epub 2011 Jan 8.

Abstract

Gallates with eight or more carbon atoms in the lateral chain show potent anticancer activity against various cell lines. However, studies regarding the in vivo antimelanoma activity of tetradecyl gallate (C(14)) have not yet been reported. In this study an evaluation of the ability of C(14) to inhibit metastasis, using lung metastases as a model, was carried out. The experimental mouse melanoma model was established by intravenous injection of metastatic B16F10 melanoma cells. The systemic toxicity of C(14) was evaluated in vivo by monitoring the weight, survival, biochemical and hematological parameters, and through histological analysis. It was observed that C(14) decreased lung metastasis in vivo by 80% and increased the survival rate of the animals without toxic effects. Additionally, C(14) induced cytotoxic effects on B16F10 cells, inhibited the inter-cellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expression, and significantly decreased cell adhesion. These results reveal that C(14) has potent antimetastatic ability and is a good candidate for further study as a potential therapeutic agent for tumor metastases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Cell Adhesion / drug effects
  • Cell Survival / drug effects
  • Female
  • Gallic Acid / analogs & derivatives*
  • Gallic Acid / pharmacology
  • Gallic Acid / therapeutic use*
  • Intercellular Adhesion Molecule-1 / metabolism
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lung Neoplasms / secondary
  • Melanoma, Experimental / drug therapy*
  • Melanoma, Experimental / metabolism
  • Melanoma, Experimental / pathology
  • Mice
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Antineoplastic Agents
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Gallic Acid