Inhibition of proliferation and invasion in 2D and 3D models by 2-methoxyestradiol in human melanoma cells

Autor(es)

Massaro, R. R. ; Faiao-Flores, F. ; Rebecca, V. W. ; Sandri, S. ; Alves-Fernandes, D. K. ; Pennacchi, P. C. ; Smalley, K. S. M. ; Maria-Engler, S. S.

• Tipo de documento: Artigo Científico
• Fonte: PHARMACOLOGICAL RESEARCH; v. 119, p. 242-250, MAR 2017.
• Citações Web of Science: 8

Resumo

Despite the recent advances in the clinical management of melanoma, there remains a need for new pharmacological approaches to treat this cancer. 2-methoxyestradiol (2ME) is a metabolite of estrogen that has shown anti-tumor effects in many cancer types. In this study we show that 2ME treatment leads to growth inhibition in melanoma cells, an effect associated with entry into senescence, decreased pRb and Cyclin B1 expression, increased p21/Cip1 expression and G2/M cell cycle arrest. 2ME treatment also inhibits melanoma cell growth in colony formation assay, including cell lines with acquired resistance to BRAF and BRAF + MEK inhibitors. We further show that 2ME is effective against melanoma with different BRAF and NRAS mutational status. Moreover, 2ME induced the retraction of cytoplasmic projections in a 3D spheroid model and significantly decreased cell proliferation in a 3D skin reconstruct model. Together our studies bring new insights into the mechanism of action of 2ME allowing melanoma targeted therapy to be further refined. Continued progress in this area is expected to lead to improved anti-cancer treatments and the development of new and more effective clinical analogues. (C) 2017 Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 10/50300-2 - Efeito do resveratrol e do 2-metoxiestradiol em linhagens de melanoma humano em modelos de monocamada e de pele reconstituida.
• Beneficiário: Renato Ramos Massaro
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 13/05172-4 - Impacto das proteínas da Transição epitélio-mesênquima em melanoma quimioresistente ao vemurabenibe
• Beneficiário: Fernanda Faião Flores
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/10821-7 - Efeito da inibição de Hsp90 nas vias de escape terapêutico de melanoma BRAF-mutado
• Beneficiário: Fernanda Faião Flores
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 14/24400-0 - Modelos in vitro para estudos pré-clínicos de melanoma quimioresistente
• Beneficiário: Silvya Stuchi Maria-Engler
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/05732-7 - Efeito do 2-metoxiestradiol na citotoxicidade e quimiorresistência de linhagens de melanoma humano
• Beneficiário: Renato Ramos Massaro
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado