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Published on: January 19, 2019

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

Bulbul Pandit1, Andrei L Gartel

  • 1Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America.

Plos One
|March 3, 2011
PubMed

Insights

The combination of thiostrepton and bortezomib shows potent anti-cancer effects by inducing apoptosis and inhibiting colony formation in human tumor cells. This synergy stems from their shared proteasome inhibitory activities.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Thiostrepton, a thiazole antibiotic, exhibits proteasome inhibitory properties.
  • Bortezomib is a known proteasome inhibitor used in cancer therapy.

Purpose of the Study:

  • To investigate the therapeutic potential of combining thiostrepton and bortezomib.
  • To evaluate the synergistic effects of this combination on human cancer cell lines.

Main Methods:

  • Treatment of various human tumor cell lines with sub-lethal concentrations of thiostrepton and bortezomib.
  • Assessment of apoptosis and long-term colony formation.
  • Quantitative analysis of drug synergy using combination index values.
  • Evaluation of a thiostrepton derivative lacking proteasome inhibitory activity.

Main Results:

  • The combination of thiostrepton and bortezomib induced potent apoptosis and inhibited long-term colony formation across diverse human cancer cell lines.
  • Combination index values were significantly below 1, indicating a strong synergistic relationship.
  • A thiostrepton derivative that did not inhibit proteasome activity failed to show synergy with bortezomib.

Conclusions:

  • Thiostrepton and bortezomib exhibit significant synergy in inhibiting human cancer cell growth.
  • The observed synergy is directly linked to the drugs' proteasome inhibitory activities.
  • This combination represents a promising therapeutic strategy for various human cancers.

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