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

[Display omitted] 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...

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Bibliographic Details
Published in:Pharmacological research 2017-05, Vol.119, p.242-250
Main Authors: Massaro, R.R., Faião-Flores, F., Rebecca, V.W., Sandri, S., Alves-Fernandes, D.K., Pennacchi, P.C., Smalley, K.S.M., Maria-Engler, S.S.
Format: Article
Language:English
Subjects:
2-methoxyestradiol
Antineoplastic Agents - pharmacology
Apoptosis - drug effects
Cell Cycle
Cell Cycle Checkpoints - drug effects
Cell Line, Tumor
Cell Proliferation - drug effects
Chemoresistance
Estradiol - analogs & derivatives
Estradiol - pharmacology
Estrogen
Humans
Melanoma
Melanoma - drug therapy
Melanoma - pathology
Neoplasm Invasiveness - pathology
Neoplasm Invasiveness - prevention & control
Skin - drug effects
Skin - pathology
Skin Neoplasms - drug therapy
Skin Neoplasms - pathology
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Summary:[Display omitted] 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.
ISSN:1043-6618
1096-1186
DOI:10.1016/j.phrs.2017.02.013