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

Author(s)

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.

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

Abstract

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: 13/05172-4 - Impact of epithelial-mesenchymal transition proteins in vemurafenib chemoresistant melanoma
• Grantee: FERNANDA FAIÃO FLORES
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/10821-7 - Hsp90 inhibition effects in therapeutic escape pathways in BRAF-mutant melanoma
• Grantee: FERNANDA FAIÃO FLORES
• Support Opportunities: 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 Opportunities: Regular Research Grants
• 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 Opportunities: Scholarships abroad - Research Internship - Doctorate