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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.)

Phosphoethanolamine induces caspase-independent cell death by reducing the expression of C-RAF and inhibits tumor growth in human melanoma model

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Author(s):
Mambelli, Lisley I. [1] ; Teixeira, Sarah F. [2] ; Jorge, Salomao D. [1, 3] ; Kawamura, Barbara [1, 4] ; Meneguelo, Renato [5] ; Barbuto, Jose A. M. [1] ; de Azevedo, Ricardo A. [1, 3] ; Ferreira, Adilson K. [1, 3, 4]
Total Authors: 8
Affiliation:
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo - Brazil
[2] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Sao Paulo - Brazil
[3] Univ Sao Paulo, Dept Oncol, CIETEC IPEN, Alchemy Innovat Res & Dev, Sao Paulo - Brazil
[4] Univ Sao Paulo, Med Sch, Med Sci, Sao Paulo - Brazil
[5] Inst Tecnol Aeronaut, Sao Jose Dos Campos, SP - Brazil
Total Affiliations: 5
Document type: Journal article
Source: BIOMEDICINE & PHARMACOTHERAPY; v. 103, p. 18-28, JUL 2018.
Web of Science Citations: 1
Abstract

Phosphoethanolamine (PEA) is a fundamental precursor during the biosynthesis of cell membranes phospholipids. In the past few years, it has been described as a potential antitumor agent. In previous studies, we demonstrated that PEA showed antitumor properties in vitro and in vivo in a wide range of tumor cell lines. Herein, we showed that PEA possesses cytotoxic properties and notably revealed to induce caspase-independent cell death. Of interest, we provided evidence that PEA inhibits melanoma cells proliferation through the reduction of C-RAF. Molecular docking of PEA evidenced that this compound indeed fits satisfactory in the binding site located between the dimers of C-RAF protein with 107,01 A and score of-29,62. Also, PEA arrested A2058 cells at G2/M phase in the cell cycle. Moreover, cell proliferation, migration and adhesion capacities of A2058 cells were also inhibited by PEA. Most importantly, PEA inhibited tumor growth of melanoma tumors and prolonged survival rate of mice. Also, PEA induced a significant immune response in a syngeneic metastatic melanoma model. Taken together, these data indicate that PEA is a promising candidate for future developments in cancer field. (AU)

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 type: Scholarships in Brazil - Post-Doctorate
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 type: Scholarships in Brazil - Doctorate
FAPESP's process: 14/14267-1 - Multi-target potentially antitumor agents for malignant melanoma: rational design, synthesis, and biological assays of novel benzofuroxan derivatives
Grantee:Salomão Dória Jorge
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 17/01265-9 - Multi-target potentially antitumor agents for malignant melanoma: rational design, synthesis, and biological assays of novel benzofuroxan derivatives
Grantee:Salomão Dória Jorge
Support type: Scholarships abroad - Research Internship - Post-doctor
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 type: Research Grants - Young Investigators Grants
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 type: Regular Research Grants