Inhibitory Effects of Indomethacin in Human MNNG/HOS Osteosarcoma Cell Line In Vitro

Cancer Invest. 2020 Jan;38(1):23-36. doi: 10.1080/07357907.2019.1698592. Epub 2019 Dec 16.

Abstract

Recurrence or metastasis remains the major cause of poor prognosis and mortality in Osteosarcoma patients. Therefore, development of more effective therapeutic approaches is required. We showed that indomethacin, significantly induces apoptosis in MNNG/HOS cell line, which was confirmed by morphological changes, increased Annexin-V + cells and nuclear fragmentation. Apoptosis was accompanied by increased cleavage of caspase-3 and PARP, suggesting activation of caspase-dependent cell death. Indomethacin significantly decreased the expression of β-catenin, a key player in tumor metastasis. These results indicate that indomethacin may have the potential to be used as neoadjuvant or adjuvant treatment; however, additional studies are required.

Keywords: Osteosarcoma; apoptosis; caspase-dependent; indomethacin; nonsteroidal anti-inflammatory drug (NSAID).

MeSH terms

  • Apoptosis / drug effects*
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / genetics
  • Bone Neoplasms / pathology
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cyclooxygenase Inhibitors / pharmacology*
  • Cyclooxygenase Inhibitors / therapeutic use
  • Drug Screening Assays, Antitumor
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Indomethacin / pharmacology*
  • Indomethacin / therapeutic use
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / genetics
  • Osteosarcoma / pathology
  • Poly(ADP-ribose) Polymerases / metabolism
  • Prognosis
  • beta Catenin / metabolism

Substances

  • CTNNB1 protein, human
  • Cyclooxygenase Inhibitors
  • beta Catenin
  • Poly(ADP-ribose) Polymerases
  • CASP3 protein, human
  • Caspase 3
  • Indomethacin