alexa Micelle-encapsulated Thiostrepton Is An Effective Nanomedicine For Inhibiting Tumor Growth
ISSN: 1948-5956

Journal of Cancer Science & Therapy
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3rd World Congress on Cancer Science & Therapy
October 21-23, 2013 DoubleTree by Hilton Hotel San Francisco Airport, CA, USA

Andrei L. Gartel
Accepted Abstracts: J Cancer Sci Ther
DOI: 10.4172/1948-5956.S1.030
Abstract
The oncogenic transcription factor FoxM1 is an attractive therapeutic target in the fight against cancer, because it is over expressed in a majority of human tumors. We identified thiazole antibiotic thiostrepton as inhibitor of FoxM1 and as proteasome inhibitor. We explored the potential in vivo anticancer properties of thiostrepton, delivered through nanoparticle encapsulation to xenograft models of breast and liver cancer. We encapsulated thiostrepton into micelles assembled from amphiphilic lipid-PEG (polyethylene glycol) molecules, where thiostrepton is solubilized within the inner lipid compartment of the micelle. Upon assembly, hydrophobic thiostrepton molecules are solubilized into the lipid component of the micelle shell, formed through the self assembly of amphipilic lipid-PEG molecules. Maximum accumulation of micelle thiostrepton nanoparticles (100 nm in diameter, -16 mV in zeta-potential) 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 of MDA-MB-231 and HepG2 cancer xenografts. Furthermore, we show for the first time the in vivo suppression of the oncogenic FOXM1 after treatment with thiostrepton. Immunoblotting and immunohistochemical staining also showed 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. Furthermore, we found that combination of thiostrepton in nanoparticles and bortezomib reduced tumor growth rates more efficiently than compared with when administered alone in xenograft and DEN-PB models of human cancer. Increased induction of apoptotic activity in tumors was found to be associated with the growth inhibitory activity of combination treatment. Further examination additionally revealed that combination-treated tumors exhibited reduced proteasome activity, compared with non-treated and single drug-treated tumors. These data suggest that this drug combination may be useful as a therapy for solid tumor
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