Thiazole antibiotic thiostrepton synergize with bortezomib to induce apoptosis in cancer cells

PLoS One. 2011 Feb 18;6(2):e17110. doi: 10.1371/journal.pone.0017110.


Thiazole antibiotic, thiostrepton was recently identified as proteasome inhibitor. We investigated the therapeutic potential of the combination of thiostrepton and proteasome inhibitor bortezomib (Velcade) on various human tumor cell lines. Combination of sub-lethal concentrations of thiostrepton and bortezomib induced potent apoptosis and inhibition of long-term colony formation in a wide variety of human cancer cell lines. The synergistic relationship between thiostrepton and bortezomib combination was also quantitatively demonstrated by calculating their combination index values that were much lower than 1 in all studied cell lines. The synergy between these drugs was based on their proteasome inhibitory activities, because thiostrepton modification, thiostrepton methyl ester, which did not have intact quinaldic acid ring and did not inhibit proteasome activity failed to demonstrate any synergy in combination with bortezomib.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Apoptosis / drug effects*
  • Boronic Acids / administration & dosage*
  • Bortezomib
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Drug Synergism
  • HCT116 Cells
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Pyrazines / administration & dosage*
  • Thiazoles / administration & dosage
  • Thiazoles / pharmacology
  • Thiostrepton / administration & dosage
  • Thiostrepton / pharmacology*


  • Antibiotics, Antineoplastic
  • Boronic Acids
  • Pyrazines
  • Thiazoles
  • Bortezomib
  • Thiostrepton