| Texto completo | |
| Autor(es): Mostrar menos - |
Cesar, Maria Carolina Mariano
;
Mortara, Renato Arruda
;
Souza, Victoria Santos
;
Alves, Vitoria Rodrigues Guimaraes
;
Paschoalin, Thaysa
;
Soufen, Marco Antonio
;
De Freitas, Guilherme Mendes
;
Da Cunha, Fernanda Fernandes Miranda
;
Da Cunha, Miranda
;
Tada, Dayane Batista
;
Dobroff, Andrey Senos
;
Arruda, Denise Costa
Número total de Autores: 12
|
| Tipo de documento: | Artigo Científico |
| Fonte: | ANTICANCER RESEARCH; v. 44, n. 1, p. 14-pg., 2024-01-01. |
| Resumo | |
Background/Aim: The Brain-Specific Homeobox/ POU Domain Protein 2 (BRN2) transcription factor supports melanoma progression by regulating the expression of several genes involved in cell migration and invasion. We hypothesized that a peptide designed based on the POU domain of BRN2 could block the BRN2 transcription activity and, consequently, reduce metastasis. Materials and Methods: Cell viability was accessed by Trypan Blue exclusion dye assay and xCelligence platform. Wound-healing scratch assay and transwell invasion with matrigel membrane assay were performed to analyze cell migration and invasion. The internalization mechanism of the L13S peptide was investigated using confocal microscopy and wound-healing scratch assay. The impact of L13S on cell protein expression was analyzed through western blotting. In vivo assays were conducted to evaluate the protective effect and toxicity of L13S in a metastatic model using murine melanoma cells. Results: Here, we show that the peptide named L13S can inhibit the migration and invasion of murine melanoma cells (B16F10-Nex2) as well as the migration of human melanoma cells (SK-MEL-25 and A375) by regulating the expression of proteins involved in motility. Mechanistically, we found that L13S is internalized by murine melanoma cells via macropinocytosis and binds actin filaments and nuclei. More importantly, in vivo studies indicated that the peptide was able to significantly inhibit lung metastasis in syngeneic models without off-target effects and with virtually no cytotoxicity toward normal organs. Conclusion: L13S peptide is a strong candidate for further development as an anticancer agent for the treatment of melanoma metastasis. (AU) | |
| Processo FAPESP: | 15/05980-9 - Determinação da atividade antitumoral induzida por peptídeos derivados do fator de transcrição Brn-2 em melanoma murino e humano |
| Beneficiário: | Denise Costa Arruda |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 22/06400-0 - Estudo dos mecanismos internalização e ação de peptídeos derivados do fator de transcrição BRN2 e de compostos naturais em células de Melanoma e Câncer de Mama |
| Beneficiário: | Denise Costa Arruda |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 16/15000-4 - Trypanosoma cruzi: variabilidade genômica intra- e interespecífica e mecanismos de invasão/evasão celular |
| Beneficiário: | Renato Arruda Mortara |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 17/01697-6 - Síntese e funcionalização de nanopartículas bimetálicas para aplicação na terapia fotodinâmica de câncer |
| Beneficiário: | Dayane Batista Tada |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 18/11972-7 - Análise da Expressão de Proteínas Reguladas pelo Fator de Transcrição Brn-2 em Células Tratadas com Peptídeos Derivados do Domínio POU da Proteína Brn-2 e Determinação da Internalização e Localização Celular desses Peptídeos |
| Beneficiário: | Denise Costa Arruda |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |