| Autor: |
Franco YA; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, Avenida Professor Lineu Prestes, Butantã 05508-000, São Paulo, Brazil., de Moraes MO Jr; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, Avenida Professor Lineu Prestes, Butantã 05508-000, São Paulo, Brazil., Carvalho LAC; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, Avenida Professor Lineu Prestes, Butantã 05508-000, São Paulo, Brazil., Dohle W; Medicinal Chemistry & Drug Discovery, Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK., da Silva RO; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, Avenida Professor Lineu Prestes, Butantã 05508-000, São Paulo, Brazil., Noma IHY; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, Avenida Professor Lineu Prestes, Butantã 05508-000, São Paulo, Brazil., Lima K; Department of Pharmacology, Biomedical Sciences Institute, University of São Paulo, Avenida Professor Lineu Prestes, Butantã 05508-000, São Paulo, Brazil., Potter BVL; Medicinal Chemistry & Drug Discovery, Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK., Machado-Neto JA; Department of Pharmacology, Biomedical Sciences Institute, University of São Paulo, Avenida Professor Lineu Prestes, Butantã 05508-000, São Paulo, Brazil., Maria-Engler SS; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, Avenida Professor Lineu Prestes, Butantã 05508-000, São Paulo, Brazil. |
| Abstrakt: |
The endogenous estradiol derivative 2-Methoxyestradiol (2-ME) has shown good and wide anticancer activity but suffers from poor oral bioavailability and extensive metabolic conjugation. However, its sulfamoylated derivative, 2-methoxyestradiol-3,17- O , O -bis-sulfamate (STX140), has superior potential as a therapeutic agent, acts by disrupting microtubule polymerization, leading to cell cycle arrest and apoptosis in cancer cells and possesses much better pharmaceutical properties. This study investigated the antiproliferative and anti-invasive activities of STX140 in both SKMEL-28 naïve melanoma (SKMEL28-P) cells and resistant melanoma cells (SKMEL-28R). STX140 inhibited cell proliferation in the nanomolar range while having a less pronounced effect on human melanocytes. Additionally, STX140 induced cell cycle arrest in the G2/M phase and sub-G1, reduced migration, and clonogenic potential in monolayer models, and inhibited invasion in a 3D human skin model with melanoma cells. Furthermore, STX140 induced senescence features in melanoma and activated the senescence machinery by upregulating the expression of senescence genes and proteins related to senescence signaling. These findings suggest that STX140 may hold potential as a therapeutic agent for melanoma treatment. |
