| Autor: |
Castro DTH; Research Group on Biotechnology and Bioprospecting Applied to Metabolism (GEBBAM), Universidade Federal da Grande Dourados, Dourados 79804-970, Brazil.; Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal da Grande Dourados, Dourados 79804-970, Brazil., Leite DF; Research Group on Biotechnology and Bioprospecting Applied to Metabolism (GEBBAM), Universidade Federal da Grande Dourados, Dourados 79804-970, Brazil., da Silva Baldivia D; Research Group on Biotechnology and Bioprospecting Applied to Metabolism (GEBBAM), Universidade Federal da Grande Dourados, Dourados 79804-970, Brazil., Dos Santos HF; Research Group on Biotechnology and Bioprospecting Applied to Metabolism (GEBBAM), Universidade Federal da Grande Dourados, Dourados 79804-970, Brazil., Balogun SO; Research Group on Biotechnology and Bioprospecting Applied to Metabolism (GEBBAM), Universidade Federal da Grande Dourados, Dourados 79804-970, Brazil.; Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal da Grande Dourados, Dourados 79804-970, Brazil., da Silva DB; Laboratory of Natural Products and Mass Spectrometry, Universidade Federal do Mato Grosso do Sul, Cidade Universitária, Campo Grande 79070-900, Brazil., Carollo CA; Laboratory of Natural Products and Mass Spectrometry, Universidade Federal do Mato Grosso do Sul, Cidade Universitária, Campo Grande 79070-900, Brazil., de Picoli Souza K; Research Group on Biotechnology and Bioprospecting Applied to Metabolism (GEBBAM), Universidade Federal da Grande Dourados, Dourados 79804-970, Brazil.; Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal da Grande Dourados, Dourados 79804-970, Brazil., Dos Santos EL; Research Group on Biotechnology and Bioprospecting Applied to Metabolism (GEBBAM), Universidade Federal da Grande Dourados, Dourados 79804-970, Brazil.; Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal da Grande Dourados, Dourados 79804-970, Brazil. |
| Abstrakt: |
In this study, a novel compound was isolated, identified, and its chemical structure was determined from the extract of the roots of Senna velutina . In addition, we sought to evaluate the anticancer potential of this molecule against melanoma and leukemic cell lines and identify the pathways of cell death involved. To this end, a novel anthraquinone was isolated from the barks of the roots of S. velutina , analyzed by HPLC-DAD, and its molecular structure was determined by nuclear magnetic resonance (NMR). Subsequently, their cytotoxic activity was evaluated by the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) method against non-cancerous, melanoma, and leukemic cells. The migration of melanoma cells was evaluated by the scratch assay. The apoptosis process, caspase-3 activation, analysis of mitochondrial membrane potential, and measurement of ROS were evaluated by flow cytometry technique. In addition, the pharmacological cell death inhibitors NEC-1, RIP-1, BAPTA, Z-VAD, and Z-DEVD were used to confirm the related cell death mechanisms. With the results, it was possible to elucidate the novel compound characterized as 2'-OH-Torosaol I. In normal cells, the compound showed no cytotoxicity in PBMC but reduced the cell viability of all melanoma and leukemic cell lines evaluated. 2'-OH-Torosaol I inhibited chemotaxis of B16F10-Nex2, SK-Mel-19, SK-Mel-28 and SK-Mel-103. The cytotoxicity of the compound was induced by apoptosis via the intrinsic pathway with reduced mitochondrial membrane potential, increased levels of reactive oxygen species, and activation of caspase-3. In addition, the inhibitors demonstrated the involvement of necroptosis and Ca 2+ in the death process and confirmed caspase-dependent apoptosis death as one of the main programmed cell death pathways induced by 2'-OH-Torosaol I. Taken together, the data characterize the novel anthraquinone 2'-OH-Torosaol I, demonstrating its anticancer activity and potential application in cancer therapy. |
