A preclinical evaluation of thiostrepton, a natural antibiotic, in nasopharyngeal carcinoma

Invest New Drugs. 2020 Apr;38(2):264-273. doi: 10.1007/s10637-019-00779-3. Epub 2019 Apr 16.

Abstract

Background Thiostrepton, a natural antibiotic, has recently been shown to be a potential anticancer drug for certain cancers, but its study in nasopharyngeal carcinoma (NPC) is still limited. The aims of this study were to investigate the anticancer effect of thiostrepton on NPC cells and to explore its underlying mechanism. Methods The effects of thiostrepton on the proliferation, migration, and invasion of NPC cells were investigated by a WST-1 assay, wound healing assay, and cell invasion assay, respectively. Microarrays were conducted and further analyzed by Ingenuity Pathways Analysis (IPA) to determine the molecular mechanism by which thiostrepton affects NPC cells. Results Our results showed that thiostrepton reduced NPC cell viability in a dose-dependent manner. Thiostrepton inhibited the migration and invasion of NPC cells in wound healing and cell invasion assays. The microarray data analyzed by IPA indicated the top 5 ingenuity canonical pathways, which were unfolded protein response, NRF2-mediated oxidative stress response, retinoate biosynthesis I, choline biosynthesis III, and pancreatic adenocarcinoma signaling. Conclusion Thiostrepton effectively suppressed NPC cell proliferation, migration, and invasion, likely by several mechanisms. Thiostrepton may be a potential therapeutic agent for treating NPC in the future.

Keywords: Anticancer drug; Microarray; Nasopharyngeal carcinoma; Thiostrepton.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Nasopharyngeal Carcinoma / drug therapy*
  • Nasopharyngeal Carcinoma / genetics
  • Nasopharyngeal Neoplasms / drug therapy*
  • Nasopharyngeal Neoplasms / genetics
  • Thiostrepton / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Thiostrepton