title: Magnetic fluid hyperthermia enhances cytotoxicity of bortezomib in sensitive and resistant cancer cell lines.
abstract: The proteasome inhibitor bortezomib (BZ) has shown promising results in some types of cancer, but in others it has had minimal activity. Recent studies have reported enhanced efficacy of BZ when combined with hyperthermia. However, the use of magnetic nanoparticles to induce hyperthermia in combination with BZ has not been reported. This novel hyperthermia modality has shown better potentiation of chemotherapeutics over other types of hyperthermia. We hypothesized that inducing hyperthermia via magnetic nanoparticles (MFH) would enhance the cytotoxicity of BZ in BZ-sensitive and BZ-resistant cancer cells more effectively than hyperthermia using a hot water bath (HWH). Studies were conducted using BZ in combination with MFH in two BZ-sensitive cell lines (MDA-MB-468, Caco-2), and one BZ-resistant cell line (A2780) at two different conditions, ie, 43°C for 30 minutes and 45°C for 30 minutes. These experiments were compared with combined application of HWH and BZ. The results indicate enhanced potentiation between hyperthermic treatment and BZ. MFH combined with BZ induced cytotoxicity in sensitive and resistant cell lines to a greater extent than HWH under the same treatment conditions. The observation that MFH sensitizes BZ-resistant cell lines makes this approach a potentially effective anticancer therapy platform.
authors.affiliation: Department of Chemical Engineering, University of Puerto Rico, Mayagüez, Puerto Rico.
authors.forename: Merlis P
authors.initials: MP
authors.lastname: Alvarez-Berríos
authors.affiliation: Department of Chemical Engineering, University of Puerto Rico, Mayagüez, Puerto Rico.
authors.forename: Amalchi
authors.initials: A
authors.lastname: Castillo
authors.affiliation: Department of Chemical Engineering, University of Puerto Rico, Mayagüez, Puerto Rico ; J Crayton Pruitt Family Department of Biomedical Engineering, Gainesville, FL, USA ; Department of Chemical Engineering, University of Florida, Gainesville, FL, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Rinaldi
authors.affiliation: Department of Chemical Engineering, University of Puerto Rico, Mayagüez, Puerto Rico.
authors.forename: Madeline
authors.initials: M
authors.lastname: Torres-Lugo
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D001897:Boronic Acids / Q000008:administration & dosage*; D000069286:Bortezomib; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy / Q000379:methods; D019008:Drug Resistance, Neoplasm / Q000528:radiation effects; D004357:Drug Synergism; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D055909:Magnetic Field Therapy / Q000379:methods*; D060526:Magnetic Fields; D058185:Magnetite Nanoparticles / Q000627:therapeutic use*; D009374:Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D011719:Pyrazines / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D058185:Magnetite Nanoparticles; D011719:Pyrazines; D000069286:Bortezomib
keywords: BZ; enhanced cytotoxicity; hot water hyperthermia; magnetic fluid hyperthermia; thermal sensitization