RESUMO
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 107,01â¯Å 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.
Assuntos
Apoptose/efeitos dos fármacos , Caspases/metabolismo , Etanolaminas/farmacologia , Melanoma/patologia , Proteínas Proto-Oncogênicas c-raf/metabolismo , Animais , Antineoplásicos/farmacologia , Sítios de Ligação , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Etanolaminas/química , Humanos , Melanoma/enzimologia , Melanoma/imunologia , Melanoma Experimental/enzimologia , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Simulação de Acoplamento Molecular , Metástase Neoplásica , Fosforilação/efeitos dos fármacos , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacosRESUMO
The X chromosome is a singular source of information in population genetics, anthropological research and in forensic cases. Thus, many researchers have been interested in characterizing X chromosome markers in different populations. The Brazilian Genetic Database of Chromosome X (BGBX--Banco Genético Brasileiro do Cromossomo X) website is freely available in Portuguese and English versions and was developed with the main purpose of compiling all Brazilian population genetic data for X chromosome short tandem repeats (X-STRs) markers published in scientific journals searchable via PubMed. Furthermore, this database presents other relevant information concerning X-STRs, such as genetic and physical locations, allele structure, nomenclature, mutation rates, primers described in the literature and likelihood ratio calculation. The entire scientific community is now encouraged to submit their X-STR population genetic data to this website, available at http://www.bgbx.com.br. Regarding future prospects of BGBX, the authors intend to expand the website with data and information of X-linked insertion-deletion polymorphisms.
