Salinomycin inhibits proliferation and induces apoptosis of human nasopharyngeal carcinoma cell in vitro and suppresses tumor growth in vivo

Biochem Biophys Res Commun. 2014 Jan 10;443(2):712-7. doi: 10.1016/j.bbrc.2013.12.032. Epub 2013 Dec 12.

Abstract

Salinomycin (Sal) is a polyether ionophore antibiotic that has recently been shown to induce cell death in various human cancer cells. However, whether salinomycin plays a functional role in nasopharyngeal carcinoma (NPC) has not been determined to date. The present study investigated the chemotherapeutic efficacy of salinomycin and its molecular mechanisms of action in NPC cells. Salinomycin efficiently inhibited proliferation and invasion of 3 NPC cell lines (CNE-1, CNE-2, and CNE-2/DDP) and activated a extensive apoptotic process that is accompanied by activation of caspase-3 and caspase-9, and decreased mitochondrial membrane potential. Meanwhile, the protein expression level of the Wnt coreceptor lipoprotein receptor related protein 6 (LRP6) and β-catenin was down-regulated, which showed that the Wnt/β-catenin signaling was involved in salinomycin-induced apoptosis of NPC cells. In a nude mouse NPC xenograft model, the anti-tumor effect of salinomycin was associated with the downregulation of β-catenin expression. The present study demonstrated that salinomycin can effectively inhibit proliferation and invasion, and induce apoptosis of NPC cells in vitro and inhibit tumor growth in vivo, probably via the inhibition of Wnt/β-catenin signaling, suggesting salinomycin as a potential candidate for the chemotherapy of NPC.

Keywords: Apoptosis; Invasion; Nasopharyngeal carcinoma; Proliferation; Wnt/β-catenin signaling.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Apoptosis / drug effects
  • Catenins / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nasopharyngeal Neoplasms / drug therapy
  • Nasopharyngeal Neoplasms / pathology*
  • Nasopharyngeal Neoplasms / physiopathology*
  • Pyrans / administration & dosage*
  • Wnt Signaling Pathway / drug effects*

Substances

  • Antineoplastic Agents
  • Catenins
  • Pyrans
  • salinomycin