Journal of Nanomedicine & Nanotechnology

Micelle-encapsulated novel proteasome inhibitor Thiostrepton is an effective nanomedicine against cancer

Joint Event on 23^rd International Conference on Nanomaterials science & Nanoengineering & Technology & International Conference and Exhibition on Pharmaceutical Nanotechnology and Nanomedicine

April 18-19, 2018 | Las Vegas, USA

Andrei L Gartel

University of Illinois at Chicago, USA

Accepted Abstracts: J Nanomed Nanotechnol

Abstract:

We identified the thiazole antibiotic thiostrepton as an inhibitor of oncogenic transcription factor FOXM1 and as a proteasome inhibitor found to induce apoptosis in cancer cells. We encapsulated thiostrepton into micelles assembled from amphiphilic lipid-PEG (polyethylene glycol) molecules and solubilized into the lipid component of the micelle shell. Maximum accumulation of micelle-thiostrepton into tumors was found at 4 hours post-administration and was retained for at least 24 hours. Upon continuous treatment, we found that nanoparticle-encapsulated thiostrepton reduced tumor growth rates human cancer xenografts. Furthermore, we showed the suppression of the oncogenic FOXM1 in vivo and increased apoptosis in the treated tumors, as indicated by cleaved caspase-3 expression. Our data suggest that the thiazole antibiotic/proteasome inhibitor thiostrepton, when formulated into nanoparticles, may be highly suited as a nanomedicine for treating human cancer. Previously, we had shown the synergic effect of proteasome inhibitors bortezomib and thiostrepton in human cancer cell lines, where sub-apoptotic concentrations of both proteasome inhibitors resulted in synergic increase in cell death when combined as a treatment. Here, we administered such a combination to xenograft tumors in vivo, and found that the combination treatment with two proteasome inhibitors reduced tumor growth rates more efficiently than compared to when administered alone. Further examination additionally revealed that combination-treated tumors exhibited reduced proteasome activity, compared to non-treated and single drug-treated tumors. In addition, we showed the efficacy of thiostrepton-micelles inhibiting tumor growth in DEN/PB hepatocellular carcinoma mouse model. We also demonstrated enhanced anti-cancer effect of the combination treatment of thiostrepton with bortezomib. Our data suggest that micelle-encapsulated thiostrepton can be used against cancer. agartel@uic.edu