Daphnetin inhibits invasion and migration of LM8 murine osteosarcoma cells by decreasing RhoA and Cdc42 expression

Biochem Biophys Res Commun. 2016 Feb 26;471(1):63-7. doi: 10.1016/j.bbrc.2016.01.179. Epub 2016 Feb 1.

Abstract

Daphnetin, 7,8-dihydroxycoumarin, present in main constituents of Daphne odora var. marginatai, has multiple pharmacological activities including anti-proliferative effects in cancer cells. In this study, using a Transwell system, we showed that daphnetin inhibited invasion and migration of highly metastatic murine osteosarcoma LM8 cells in a dose-dependent manner. Following treatment by daphnetin, cells that penetrated the Transwell membrane were rounder than non-treated cells. Immunofluorescence analysis revealed that daphnetin decreased the numbers of intracellular stress fibers and filopodia. Moreover, daphnetin treatment dramatically decreased the expression levels of RhoA and Cdc42. In summary, the dihydroxycoumarin derivative daphnetin inhibits the invasion and migration of LM8 cells, and therefore represents a promising agent for use against metastatic cancer.

Keywords: Filopodia; LM8; Metastasis; Rho family small GTP-binding proteins; Stress fiber; daphnetin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Mice
  • Neoplasm Invasiveness
  • Osteosarcoma / drug therapy
  • Osteosarcoma / pathology*
  • Osteosarcoma / physiopathology*
  • Umbelliferones / administration & dosage*
  • cdc42 GTP-Binding Protein / metabolism*
  • rhoA GTP-Binding Protein / metabolism*

Substances

  • Antineoplastic Agents
  • Cdc42 protein, mouse
  • Umbelliferones
  • cdc42 GTP-Binding Protein
  • rhoA GTP-Binding Protein
  • daphnetin