Edelfosine: An Antitumor Drug Prototype
Autor: | Lisley I. Mambelli, Emer S. Ferro, Adilson Kleber Ferreira, Thais Narimatsu Pettinati, Salomão Dória Jorge, Sarah Fernandes Teixeira, Cícero Júlio Silva Costa, Cecilia Pessoa Rodrigues, José Alexandre Marzagão Barbuto, Rodrigo Nalio Ramos, Ricardo A. Azevedo |
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Rok vydání: | 2017 |
Předmět: |
Cancer Research
Lung Neoplasms Cell Survival Surface Properties Molecular Conformation Antineoplastic Agents Apoptosis 02 engineering and technology Flow cytometry 03 medical and health sciences chemistry.chemical_compound Structure-Activity Relationship 0302 clinical medicine In vivo medicine Tumor Cells Cultured Cytotoxic T cell Humans MTT assay Particle Size Clonogenic assay Cell Proliferation Pharmacology A549 cell Membrane Potential Mitochondrial medicine.diagnostic_test Dose-Response Relationship Drug Chemistry Cell Cycle Cancer Phospholipid Ethers 021001 nanoscience & nanotechnology medicine.disease CITOTOXICIDADE IMUNOLÓGICA A549 Cells 030220 oncology & carcinogenesis Cancer research Molecular Medicine Drug Screening Assays Antitumor 0210 nano-technology Edelfosine |
Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
ISSN: | 1875-5992 |
Popis: | Background: Lung cancer is the most prevalent cancer and a high fatality disease. Despite of all available therapeutic approaches, drug resistance of chemotherapy agents for patients remain as an obstacle. New drugs integrating immunotherapeutic and conventional cytotoxic effects is a powerful strategy for the treatment of cancer to overcome this limitation. Antineoplastic phospholipids combine both of these activities by affecting lipid metabolism and signaling through lipid rafts. Therefore, they emerge as interesting scaffolds for designing new drugs. Objective: We aimed to evaluate antineoplastic phospholipids as scaffolds for designing new drugs for lung cancer treatment. Methods: The initial screening in A549 cells was performed by MTT assay. Others cytotoxic effects were evaluated in A549 cells by clonogenic assay, Matrigel 3D culture and flow cytometry analyses of cell cycle, apoptosis, mitochondrial membrane electronic potential and superoxide production. Immunological effects of ED were accessed on dendritic cells (DCs) and the expression of some markers were evaluated by flow cytometry. In vivo lung colonization analysis was performed after intravenously injection of A549 cells and daily treatment with ED. Results: Herein, ED showed to be the most efficient compound concerning cytotoxic, thereby, ED was selected for following tests. ED showed a cytotoxic profile in both monolayer and 3D culture and also in vivo models using A549 cells. This profile is due to G0/G1 phase cellular arrest and apoptosis drove by mitochondrial membrane depolarization and superoxide overproduction. Moreover, ED modulated DCs toward an activated pattern by the increased expression of CD83 and a remarkable decreased expression of PD-L1/CD274 on DCs membrane. Conclusions: Thus, ED is an interesting antitumor drug prototype due to not only its direct cellular cytotoxicity but also given its immunological features. |
Databáze: | OpenAIRE |
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