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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Edelfosine: An Antitumor Drug Prototype

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Teixeira, Sarah F. [1, 2] ; Rodrigues, Cecilia P. [2] ; Costa, Cicero J. S. [2] ; Pettinati, Thais N. [2] ; de Azevedo, Ricardo A. [3] ; Mambelli, I, Lisley ; Jorge, Salomao D. [3, 4] ; Ramos, Rodrigo N. [4] ; Ferro, Emer S. [1] ; Barbuto, Jose A. M. [4] ; Ferreira, Adilson K. [5, 3, 4]
Total Authors: 11
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Sao Paulo - Brazil
[2] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo - Brazil
[3] Univ Sao Paulo, CIETEC IPEN, Dept Oncol, Alchemy Innovat Res & Dev, Sao Paulo - Brazil
[4] Mambelli, Lisley, I, Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo - Brazil
[5] Univ Sao Paulo, Med Sch, Med Sci, Sao Paulo - Brazil
Total Affiliations: 5
Document type: Journal article
Source: ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY; v. 18, n. 6, p. 865-874, 2018.
Web of Science Citations: 1

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. (AU)

FAPESP's process: 15/18528-7 - Development of new drug candidate for the treatment of non-small cell lung cancer: CHY-1 as a novel inhibitor of autophagy and prototype of a novel class of inhibitors of the enzyme CTP: phosphoethanolamine citidililtransferase
Grantee:Adilson Kleber Ferreira
Support Opportunities: Research Grants - Young Investigators Grants
FAPESP's process: 16/07519-0 - Development of CHY-1 as a new drug candidate for the treatment of different types of breast cancer
Grantee:Lisley Inata Mambelli
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 14/24455-0 - Evaluation of the activity of CHY-1, a novel miltefosine analogue, as a potential CTP: phosphoethanolamine cytidylyltransferase enzyme inhibitor, against non-small cell lung câncer
Grantee:Sarah Fernandes Teixeira
Support Opportunities: Scholarships in Brazil - Master
FAPESP's process: 16/09392-7 - Validation of CTP:phosphoethanolamine cytidylyltransferase enzyme and ethanolamine transport as new targets for the rational development of new drugs in Non-Small Cell Lung Cancer treatment
Grantee:Sarah Fernandes Teixeira
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 13/07273-2 - Rational design and development of new prototypes derived of antitumor phospholipids as potential inhibitors of the enzyme CtP: phosphoethanolamine citidililtransferase and antitumor agents in non-small cell lung cancer
Grantee:Jose Alexandre Marzagão Barbuto
Support Opportunities: Regular Research Grants