Melarsomine suppresses canine osteosarcoma cell survival via inhibition of Hedgehog-GLI signaling.

Abstract

The Hedgehog-GLI signaling pathway is activated in human and canine osteosarcoma (OSA) and represents a potential therapeutic target for cancers, including OSA. Arsenic trioxide represses GLI expression. Melarsomine, an arsenic compound-containing drug, has been approved for the treatment of canine heartworm disease. Hence, we hypothesized that melarsomine inhibits GLI signaling in canine OSA cell lines. The present study aimed to assess this hypothesis. Cell viability and colony formation were decreased in the canine OSA cell lines Abrams and D17 after treatment with melarsomine. Melarsomine-induced apoptotic cell death was assessed via cell cycle analysis using propidium iodide staining. Quantitative real-time reverse transcription polymerase chain reaction and western blot analyses revealed a downregulation of genes downstream of the Hedgehog signaling pathway, including GLI1, GLI2, and PTCH, after melarsomine treatment. The present results suggest that melarsomine exerts antitumor effects and serves as a GLI inhibitor in canine OSA cells. Additional studies are required to evaluate and confirm the anticancer effect and relevant therapeutic dose of melarsomine in vivo.