title: Combination with bortezomib enhances the antitumor effects of nanoparticle-encapsulated thiostrepton.
abstract: Bortezomib is well-known for inducing cell death in cancer cells, specifically through the mechanism of proteasome inhibition. Thiostrepton, a thiazole antibiotic, has also been described for its proteasome inhibitory action, although differing slightly to bortezomib in the proteasomal site to which it is active. Previously we had shown the synergic effect of bortezomib and thiostrepton in breast cancer cells in vitro, 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 MDA-MB-231 xenograft tumors in vivo, and found that the effect of complementary proteasome inhibitors reduced tumor growth rates more efficiently than compared with when administered alone. Increased induction of apoptotic activity in tumors was found 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 tumors.
authors.affiliation: Department of Medicine; University of Illinois at Chicago; Chicago, IL USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
authors.forename: Andrei L
authors.initials: AL
authors.lastname: Gartel
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D053769:Nanocapsules / Q000008:administration & dosage; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011719:Pyrazines / Q000008:administration & dosage; D011897:Random Allocation; D013883:Thiostrepton / Q000008:administration & dosage; D014018:Tissue Distribution; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D001897:Boronic Acids; D053769:Nanocapsules; D011719:Pyrazines; D000069286:Bortezomib; D046988:Proteasome Endopeptidase Complex; D013883:Thiostrepton