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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.)

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

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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.
Total Authors: 8
Document type: Journal article
Source: PHARMACOLOGICAL RESEARCH; v. 119, p. 242-250, MAR 2017.
Web of Science Citations: 8

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)

FAPESP's process: 15/10821-7 - Hsp90 inhibition effects in therapeutic escape pathways in BRAF-mutant melanoma
Grantee:Fernanda Faião Flores
Support type: Scholarships abroad - Research Internship - Post-doctor
FAPESP's process: 14/24400-0 - In vitro models for pre clinical studies of melanoma Chemoresistant
Grantee:Silvya Stuchi Maria-Engler
Support type: Regular Research Grants
FAPESP's process: 13/05172-4 - Impact of epithelial-mesenchymal transition proteins in vemurafenib chemoresistant melanoma
Grantee:Fernanda Faião Flores
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 12/05732-7 - Effect of 2-methoxiestradiol in the citotoxicity and chemorresistance of human melanoma cell lines
Grantee:Renato Ramos Massaro
Support type: Scholarships abroad - Research Internship - Doctorate