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Current pharmacological treatments for melanoma are not completely effective, requiring the identification of new drugs. As an alternative, plant-derived natural compounds are described as promising sources of new anticancer drugs. In this context, the objectives of this study were to identify the chemical composition of the ethanolic extract of <jats:italic>Senna velutina<\/jats:italic> roots (ESVR), to assess its <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> antitumor effects on melanoma cells, and to characterize its mechanisms of action. For these purposes, the chemical constituents were identified by liquid chromatography coupled to high-resolution mass spectrometry. The <jats:italic>in vitro<\/jats:italic> activity of the extract was assessed in the B16F10-Nex2 melanoma cell line using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and based on the apoptotic cell count; DNA fragmentation; necrostatin-1 inhibition; intracellular calcium, pan-caspase, and caspase-3 activation; reactive oxygen species (ROS) levels; and cell cycle arrest. The <jats:italic>in vivo<\/jats:italic> activity of the extract was assessed in models of tumor volume progression and pulmonary nodule formation in C57Bl\/6 mice. The chemical composition results showed that ESVR contains flavonoid derivatives of the catechin, anthraquinone, and piceatannol groups. The extract reduced B16F10-Nex2 cell viability and promoted apoptotic cell death as well as caspase-3 activation, with increased intracellular calcium and ROS levels as well as cell cycle arrest at the sub-G<jats:sub>0<\/jats:sub>\/G<jats:sub>1<\/jats:sub> phase. <jats:italic>In vivo<\/jats:italic>, the tumor volume progression and pulmonary metastasis of ESVR-treated mice decreased over 50%. Combined, these results show that ESVR had <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> antitumor effects, predominantly by apoptosis, thus demonstrating its potential as a therapeutic agent in the treatment of melanoma and other types of cancer.<\/jats:p>","DOI":"10.1155\/2019\/5719483","type":"journal-article","created":{"date-parts":[[2019,6,12]],"date-time":"2019-06-12T19:31:32Z","timestamp":1560367892000},"page":"1-14","source":"Crossref","is-referenced-by-count":14,"title":["Ethanolic Extract of <i>Senna velutina<\/i> Roots: Chemical Composition, <i>In Vitro<\/i> and <i>In Vivo<\/i> Antitumor Effects, and B16F10-Nex2 Melanoma Cell Death Mechanisms"],"prefix":"10.1155","volume":"2019","author":[{"given":"David Tsuyoshi Hiramatsu","family":"Castro","sequence":"first","affiliation":[{"name":"Research Group on Biotechnology and Bioprospecting Applied to Metabolism (GEBBAM), Federal University of Grande Dourados, Dourados, CEP: 79804-970 MS, 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