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

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posted on 27.05.2011 by Bulbul Pandit, Andrei L. Gartel
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.

Funding

Funding was provided by National Institutes of Health grants 1RO1CA1294414 and 1R21CA134615 (A.L. Gartel).

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Publisher Statement

The original source for this publication is at Public Library of Science; DOI: 10.1371/journal.pone.0017110. © 2011 Pandit, Gartel. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publisher

Public Library of Science

Language

en_US

issn

1932-6203

Issue date

18/02/2011

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