Peptide R18H from BRN2 Transcription Factor POU Domain Displays Antitumor Activity In Vitro and In Vivo and Induces Apoptosis in B16F10-Nex2 Cells

Autor(es):Mostrar menos -

da Cunha, Fernanda F. M. ^[1] ; Mugnol, Katia C. U. ^[2] ; de Melo, Filipe M. ^[3] ; Nascimento, Marta V. S. Q. ^[2] ; de Azevedo, Ricardo A. ^[4] ; Santos, Raquel T. S. ^[1] ; Magalhaes, Jessica A. ^[5] ; Miguel, Danilo C. ^[6] ; Tada, Dayane B. ^[5] ; Mortara, Renato A. ^[7] ; Travassos, Luiz R. ^[4] ; Arruda, Denise C. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Mogi das Cruzes, NIB, Mogi das Cruzes, SP - Brazil

^[2] Univ Mogi das Cruzes, CIIB, Mogi das Cruzes, SP - Brazil

^[3] Univ Fed Sao Paulo UNIFESP, Dept Imunol, Escola Paulista Med, Sao Paulo, SP - Brazil

^[4] Univ Fed Sao Paulo UNIFESP, Escola Paulista Med, Unidade Oncol Expt UNONEX, Sao Paulo, SP - Brazil

^[5] Univ Fed Sao Paulo UNIFESP, Inst Ciencia & Tecnol, Lab Nanomat & Nanotoxicol, Sao Jose Dos Campos, SP - Brazil

^[6] Univ Estadual Campinas, Inst Biol, Dept Biol Anim, UNICAMP, Campinas, SP - Brazil

^[7] Univ Fed Sao Paulo UNIFESP, Dept Microbiol Imunol & Parasitol, Escola Paulista Med, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY; v. 19, n. 3, p. 389-401, 2019.
• Citações Web of Science: 0

Resumo

Background: BRN2 transcription factor is associated with the development of malignant melanoma. The cytotoxic activities and cell death mechanism against B16F10-Nex2 cells were determined with synthetic peptide R18H derived from the POU domain of the BRN2 transcription factor. Objective: To determine the cell death mechanisms and in vivo activity of peptide R18H derived from the POU domain of the BRN2 transcription factor against BI6F10-Nex2 cells. Methods: Cell viability was determined by the MTT method. C57Bl/6 mice were challenged with B16F10-Nex2 cells and treated with R18H. To identify the type of cell death, we used TUNEL assay, Annexin V and PI, Hoechst, DHE, and determination of caspase activation and cytochrome c release. Transmission electron microscopy was performed to verify morphological alterations after peptide treatment. Results: Peptide R18H displayed antitumor activity in the first hours of treatment and the EC50% was calculated for 2 and 24h, being 0.76 +/- 0.045 mM and 0.559 +/- 0.053 mM, respectively. After 24h apoptosis was evident, based on DNA degradation, chromatin condensation, increase of superoxide anion production, phosphatidylserine translocation, activation of caspases 3 and 8, and release of extracellular cytochrome c in B16F10-Nex2 cells. The peptide cytotoxic activity was not affected by necroptosis inhibitors and treated cells did not release LDH in the extracellular medium. Moreover, in vivo antitumor activity was observed following treatment with peptide R18H. Conclusion: Peptide R18H from BRN2 transcription factor induced apoptosis in B16F10-Nex2 and displayed antitumor activity in vivo. (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: 14/21129-4 - O papel das proteínas ligantes de ácidos graxos na infecção de macrófagos por Leishmania: um alvo potencial para novas drogas contra leishmaniose
• Beneficiário: Danilo Ciccone Miguel
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores