title: Synergistic anti-tumor effects of the combination of a benzofuroxan derivate and sorafenib on NCI-H460 human large cell lung carcinoma cells.
abstract: Lung cancer is the most frequent and lethal human cancer in the world. Because is still an unsolved health issue, new compounds or therapeutic strategies are urgently needed. Furoxans are presented as potentials candidates for lung cancer treatment. Accordingly, we evaluated the efficacy of a benzofuroxan derivative, BFD-22, alone and combined with sorafenib against NCI-H460 cell line. We showed that BFD-22 has cytotoxic effects on the NCI-H460 cells. Importantly, the Combination Index (CI) evaluation revels that BFD-22 combined with sorafenib has a stronger cytotoxic effect. In addition, the combination induces apoptosis through extrinsic pathway, leading to TRAIL-R1/DR4-triggered apoptosis. Furthermore, BFD-22 combined with sorafenib increases ROS production and simultaneously reduces perlecan expression in the NCI-H460 cells. In accordance, tumor cells were arrested in the S-phase, and these anti-proliferative effects also inhibit cell migration. This is the first study reporting an advantage of BFD-22 combined with sorafenib as a new therapeutic strategy in the fight against lung cancer.
authors.affiliation: Laboratory of Tumor Immunology, Department of Immunology, Institute of Biomedical Science, University of São Paulo, avenue Prof. Lineu-Prestes, 1730 São Paulo - SP, Brazil.
authors.forename: Sarah Fernandes
authors.initials: SF
authors.lastname: Teixeira
authors.affiliation: Laboratory of Tumor Immunology, Department of Immunology, Institute of Biomedical Science, University of São Paulo, avenue Prof. Lineu-Prestes, 1730 São Paulo - SP, Brazil.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Alexandre de Azevedo
authors.affiliation: Laboratory of Tumor Immunology, Department of Immunology, Institute of Biomedical Science, University of São Paulo, avenue Prof. Lineu-Prestes, 1730 São Paulo - SP, Brazil.
authors.forename: Maria Alejandra Clavijo
authors.initials: MA
authors.lastname: Salomon
authors.affiliation: Laboratory of Tumor Immunology, Department of Immunology, Institute of Biomedical Science, University of São Paulo, avenue Prof. Lineu-Prestes, 1730 São Paulo - SP, Brazil.
authors.forename: Salomão Dória
authors.initials: SD
authors.lastname: Jorge
authors.affiliation: Laboratory of Genetics and Molecular Hematology (LIM31), University of São Paulo School of Medicine, São Paulo - SP, Brazil.
authors.forename: Débora
authors.initials: D
authors.lastname: Levy
authors.affiliation: Laboratory of Genetics and Molecular Hematology (LIM31), University of São Paulo School of Medicine, São Paulo - SP, Brazil.
authors.forename: Sérgio Paulo
authors.initials: SP
authors.lastname: Bydlowski
authors.affiliation: Laboratory of Tumor Immunology, Department of Immunology, Institute of Biomedical Science, University of São Paulo, avenue Prof. Lineu-Prestes, 1730 São Paulo - SP, Brazil.
authors.forename: Cecília Pessoa
authors.initials: CP
authors.lastname: Rodrigues
authors.affiliation: Laboratory of Tumor Immunology, Department of Immunology, Institute of Biomedical Science, University of São Paulo, avenue Prof. Lineu-Prestes, 1730 São Paulo - SP, Brazil.
authors.forename: Célia Regina
authors.initials: CR
authors.lastname: Pizzo
authors.affiliation: Laboratory of Tumor Immunology, Department of Immunology, Institute of Biomedical Science, University of São Paulo, avenue Prof. Lineu-Prestes, 1730 São Paulo - SP, Brazil; Cell and Molecular Therapy Center NUCEL-NETCEM, University of São Paulo, São Paulo - SP, Brazil.
authors.forename: José Alexandre Marzagão
authors.initials: JA
authors.lastname: Barbuto
authors.affiliation: Laboratory of Tumor Immunology, Department of Immunology, Institute of Biomedical Science, University of São Paulo, avenue Prof. Lineu-Prestes, 1730 São Paulo - SP, Brazil. Electronic address: ferreira-kleber@usp.br.
authors.forename: Adilson Kleber
authors.initials: AK
authors.lastname: Ferreira
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001583:Benzoxazoles / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010671:Phenylurea Compounds / Q000008:administration & dosage*; D000077157:Sorafenib; D010069:Oxadiazoles
chemical_list: D000970:Antineoplastic Agents; D001583:Benzoxazoles; D009536:Niacinamide; D010671:Phenylurea Compounds; D000077157:Sorafenib; C014354:benzofuroxan; D010069:Oxadiazoles
keywords: Anti-proliferative; Apoptosis; BFD-22; Furoxan; Lung cancer; Sorafenib