SNX-2112 Induces Apoptosis and Autophagy of Nara-H Cells

Anticancer Res. 2018 Sep;38(9):5177-5181. doi: 10.21873/anticanres.12840.

Abstract

Background/aim: Selective heat shock protein 90 (Hsp90) inhibitor SNX-2112 exhibits antitumor activity in multiple cancer cell types. Here, the antitumor activity of SNX-2112 in Nara-H cells was analyzed.

Materials and methods: Antitumor activity of SNX-2112 was assessed using a cell proliferation assay. We also examined the signalling pathways involved in SNX-2112-mediated autophagy and apoptosis of Nara-H cells by western blot and morphological analyses.

Results: Cell proliferation assays demonstrated that SNX-2112 inhibited Nara-H cell growth. Western blotting revealed that SNX-2112 induced apoptosis and autophagy, inhibited mammalian target of rapamycin (mTOR) phosphorylation, and suppressed the mitogen-activated protein kinase (MAPK) signalling pathway. Morphological analysis confirmed that SNX-2112 induced autophagy and apoptosis.

Conclusion: SNX-2112 induced autophagy and apoptosis of Nara-H cells by inhibiting mTOR and MAPK pathways. Our results support developing SNX-2112 to treat human soft tissue sarcomas.

Keywords: SNX-2112; apoptosis; autophagy; undifferentiated pleomorphic sarcoma.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • Autophagy
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic / drug effects
  • Heterocyclic Compounds, 4 or More Rings / pharmacology*
  • Humans
  • MAP Kinase Signaling System / drug effects*
  • Phosphorylation / drug effects
  • Sarcoma / drug therapy
  • Sarcoma / metabolism*
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Antineoplastic Agents
  • Heterocyclic Compounds, 4 or More Rings
  • SNX 2112
  • MTOR protein, human
  • TOR Serine-Threonine Kinases