Melarsomine suppresses canine osteosarcoma cell survival via inhibition of hedgehog-GLI signalling

Aryung Nam, Taewon Kim, Qiang Li, Robert B. Rebhun, Hwa Young Youn, Kyoung Won Seo

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1722-1729
Number of pages8
JournalJournal of Veterinary Medical Science
Volume81
Issue number12
DOIs
StatePublished - Dec 2019

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osteosarcoma
Erinaceidae
Osteosarcoma
cell viability
Canidae
Cell Survival
dogs
cell lines
arsenicals
therapeutics
heartworms
Dirofilariasis
arsenic
Dog Diseases
Arsenicals
Cell Line
cell death
cell cycle
Propidium
quantitative polymerase chain reaction

Keywords

  • Dog
  • GLI
  • Hedgehog signaling pathway
  • Melarsomine
  • Osteosarcoma

ASJC Scopus subject areas

  • veterinary(all)

Cite this

Melarsomine suppresses canine osteosarcoma cell survival via inhibition of hedgehog-GLI signalling. / Nam, Aryung; Kim, Taewon; Li, Qiang; Rebhun, Robert B.; Youn, Hwa Young; Seo, Kyoung Won.

In: Journal of Veterinary Medical Science, Vol. 81, No. 12, 12.2019, p. 1722-1729.

Research output: Contribution to journalArticle

Nam, Aryung ; Kim, Taewon ; Li, Qiang ; Rebhun, Robert B. ; Youn, Hwa Young ; Seo, Kyoung Won. / Melarsomine suppresses canine osteosarcoma cell survival via inhibition of hedgehog-GLI signalling. In: Journal of Veterinary Medical Science. 2019 ; Vol. 81, No. 12. pp. 1722-1729.
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