Structural Characterization and Anticancer Activity of a New Anthraquinone from Senna velutina (Fabaceae)

David Tsuyoshi Hiramatsu Castro; Daniel Ferreira Leite; Debora da Silva Baldivia; Helder Freitas Dos Santos; Sikiru Olaitan Balogun; Denise Brentan da Silva; Carlos Alexandre Carollo; Kely de Picoli Souza; Edson Lucas Dos Santos

doi:10.3390/ph16070951

Structural Characterization and Anticancer Activity of a New Anthraquinone from Senna velutina (Fabaceae)

Pharmaceuticals (Basel). 2023 Jul 1;16(7):951. doi: 10.3390/ph16070951.

Affiliations

¹ Research Group on Biotechnology and Bioprospecting Applied to Metabolism (GEBBAM), Universidade Federal da Grande Dourados, Dourados 79804-970, Brazil.
² Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal da Grande Dourados, Dourados 79804-970, Brazil.
³ Laboratory of Natural Products and Mass Spectrometry, Universidade Federal do Mato Grosso do Sul, Cidade Universitária, Campo Grande 79070-900, Brazil.

Abstract

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 Ca²⁺ 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.

Keywords: anthracene; caspase; leukemia; medicinal plants; melanoma.

Grants and funding

This work was supported by institutional funding from the Fundação de Apoio ao Desenvolvimento do Ensino, Ciência e Tecnologia do Estado de Mato Grosso do Sul (FUNDECT, Brazil), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Brazil) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil).