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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Published in | Pharmacological research Vol. 119; pp. 242 - 250 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
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Elsevier Ltd
01.05.2017
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Abstract | [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. |
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AbstractList | [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. 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. 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 CyclinB1 expression, increased p21/Cip1 expression and G2/M cell cycle arrest. 2ME treatment also inhibits melanoma cell growth in colony formation assays, 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. |
Author | Rebecca, V.W. Smalley, K.S.M. Faião-Flores, F. Pennacchi, P.C. Alves-Fernandes, D.K. Sandri, S. Maria-Engler, S.S. Massaro, R.R. |
AuthorAffiliation | 2 The Department of Tumor Biology, The Moffitt Cancer Center & Research Institute, Tampa, USA 1 Department of Clinical Chemistry & Toxicology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil |
AuthorAffiliation_xml | – name: 1 Department of Clinical Chemistry & Toxicology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil – name: 2 The Department of Tumor Biology, The Moffitt Cancer Center & Research Institute, Tampa, USA |
Author_xml | – sequence: 1 givenname: R.R. surname: Massaro fullname: Massaro, R.R. organization: Department of Clinical Chemistry & Toxicology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil – sequence: 2 givenname: F. surname: Faião-Flores fullname: Faião-Flores, F. organization: Department of Clinical Chemistry & Toxicology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil – sequence: 3 givenname: V.W. surname: Rebecca fullname: Rebecca, V.W. organization: The Department of Tumor Biology, The Moffitt Cancer Center & Research Institute, Tampa, USA – sequence: 4 givenname: S. surname: Sandri fullname: Sandri, S. organization: Department of Clinical Chemistry & Toxicology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil – sequence: 5 givenname: D.K. surname: Alves-Fernandes fullname: Alves-Fernandes, D.K. organization: Department of Clinical Chemistry & Toxicology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil – sequence: 6 givenname: P.C. surname: Pennacchi fullname: Pennacchi, P.C. organization: Department of Clinical Chemistry & Toxicology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil – sequence: 7 givenname: K.S.M. surname: Smalley fullname: Smalley, K.S.M. organization: The Department of Tumor Biology, The Moffitt Cancer Center & Research Institute, Tampa, USA – sequence: 8 givenname: S.S. surname: Maria-Engler fullname: Maria-Engler, S.S. email: silvya@usp.br organization: Department of Clinical Chemistry & Toxicology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil |
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Keywords | Melanoma 2-methoxyestradiol Estrogen Chemoresistance |
Language | English |
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Despite the recent advances in the clinical management of melanoma, there remains a need for new pharmacological approaches to treat this... Despite the recent advances in the clinical management of melanoma, there remains a need for new pharmacological approaches to treat this cancer.... |
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SubjectTerms | 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 |
Title | Inhibition of proliferation and invasion in 2D and 3D models by 2-methoxyestradiol in human melanoma cells |
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