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

被引：8

作者：

Castro, David Tsuyoshi Hiramatsu ^{[1
,2
]}

Leite, Daniel Ferreira ^{[1
]}

Baldivia, Debora da Silva ^{[1
]}

dos Santos, Helder Freitas ^{[1
]}

Balogun, Sikiru Olaitan ^{[1
,2
]}

da Silva, Denise Brentan ^{[3
]}

Carollo, Carlos Alexandre ^{[3
]}

Souza, Kely de Picoli ^{[1
,2
]}

dos Santos, Edson Lucas ^{[1
,2
]}

机构：

[1] Fundacao Univ Fed Grande Dourados, Res Grp Biotechnol & Bioprospecting Appl Metab GEB, BR-79804970 Dourados, Brazil

[2] Fundacao Univ Fed Grande Dourados, Programa Posgrad Ciencias Saude, BR-79804970 Dourados, Brazil

[3] Univ Fed Mato Grosso Do Sul, Lab Nat Prod & Mass Spectrometry, Cidade Univ, BR-79070900 Campo Grande, Brazil

来源：

PHARMACEUTICALS | 2023年 / 16卷 / 07期

关键词：

melanoma; leukemia; medicinal plants; anthracene; caspase; APOPTOSIS; ACTIVATION; MECHANISMS; AGENTS; DEATH; CELLS;

D O I：

10.3390/ph16070951

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 & PRIME;-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 & PRIME;-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 & PRIME;-OH-Torosaol I. Taken together, the data characterize the novel anthraquinone 2 & PRIME;-OH-Torosaol I, demonstrating its anticancer activity and potential application in cancer therapy.

引用

页数：21

共 67 条

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