In Vitro and In Vivo Anti-Melanoma Effects of Pituranthos tortuosus Essential Oil Via Inhibition of FAK and Src Activities

J Cell Biochem. 2016 May;117(5):1167-75. doi: 10.1002/jcb.25400. Epub 2015 Oct 18.

Abstract

A large number of plants used in traditional medicines have been shown to possess antitumor activities. The aims of this study were to evaluate any anticancer effect of the essential oil (EO) extracted from P. tortuosus against B16F10 melanoma cancer cells in vitro as well as in vivo. In vitro, EO was shown to induce apoptosis and to inhibit migration and invasion processes. Further investigation revealed that EO decreased focal adhesion and invadopodia formation which was accompanied by a drastic downregulation of FAK, Src, ERK, p130Cas and paxillin. Moreover, EO treatment decreased the expression level of p190RhoGAP, and Grb2, which impair cell migration and actin assembly. Mice bearing the melanoma cells were used to confirm any in vivo effectiveness of the EO as an anti-tumor promoting agent. In mice dosed with 100 mg EO/kg/d (for 27 days), tumor weight was inhibited by 98% compared to that in mice that did not receive the product. In conclusion, these data suggested to us that an EO of P. tortuosus could evolve to be a potential medicinal resource for use in the treatment of cancers.

Keywords: ANTI-TUMOR; EO; FAK; INVASION; MELANOMA; MIGRATION; Src.

MeSH terms

  • Animals
  • Apiaceae / chemistry*
  • Apoptosis / drug effects
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Focal Adhesion Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism
  • Focal Adhesions / drug effects
  • Humans
  • Melanoma, Experimental / drug therapy*
  • Melanoma, Experimental / metabolism
  • Melanoma, Experimental / pathology
  • Mice, Inbred BALB C
  • Neoplasm Invasiveness
  • Oils, Volatile / pharmacology*
  • Phytotherapy
  • Proto-Oncogene Proteins pp60(c-src) / antagonists & inhibitors*
  • Proto-Oncogene Proteins pp60(c-src) / metabolism
  • Tumor Burden / drug effects

Substances

  • Oils, Volatile
  • Focal Adhesion Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins pp60(c-src)