Almeida Alisson A, Lima Graziela D A, Simão Marcos V R C, Moreira Gabriela A, Siqueira Raoni P, Zanatta Ana C, Vilegas Wagner, Machado-Neves Mariana, Bressan Gustavo C, Leite João P V
Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa, Minas Gerais, Brazil.
Departamento de Biologia Geral, Universidade Federal de Viçosa, Minas Gerais, Brazil.
Int J Exp Pathol. 2020 Jun;101(3-4):106-121. doi: 10.1111/iep.12351. Epub 2020 May 26.
Plant biodiversity is a source of potential natural products for the treatment of many diseases. One of the ways of discovering new drugs is through the cytotoxic screening of extract libraries. The present study evaluated 196 extracts prepared by maceration of Brazilian Atlantic Forest trees with organic solvents and distilled water for cytotoxic and antimetastatic activity. The MTT assay was used to screen the extract activity in MCF-7, HepG2 and B16F10 cancer cells. The highest cytotoxic extract had antimetastatic activity, as determined in in vitro assays and melanoma murine model. The organic extract of the leaves of Athenaea velutina (EAv) significantly inhibited migration, adhesion, invasion and cell colony formation in B16F10 cells. The phenolic compounds and flavonoids in EAv were identified for the first time, using flow injection with electrospray negative ionization-ion trap tandem mass spectrometry analysis (FIA-ESI-IT-MS ). EAv markedly suppressed the development of pulmonary melanomas following the intravenous injection of melanoma cells to C57BL/6 mice. Stereological analysis of the spleen cross-sections showed enlargement of the red pulp area after EAv treatment, which indicated the activation of the haematopoietic system. The treatment of melanoma-bearing mice with EAv did not result in liver damage. In conclusion, these findings suggest that A velutina is a source of natural products with potent antimetastatic activity.
植物生物多样性是治疗多种疾病的潜在天然产物来源。发现新药的方法之一是通过对提取物文库进行细胞毒性筛选。本研究评估了用有机溶剂和蒸馏水浸渍巴西大西洋森林树木制备的196种提取物的细胞毒性和抗转移活性。采用MTT法筛选提取物在MCF-7、HepG2和B16F10癌细胞中的活性。在体外试验和黑色素瘤小鼠模型中确定,细胞毒性最高的提取物具有抗转移活性。天鹅绒雅典娜树叶的有机提取物(EAv)显著抑制B16F10细胞的迁移、粘附、侵袭和细胞集落形成。使用流动注射电喷雾负离子-离子阱串联质谱分析(FIA-ESI-IT-MS)首次鉴定了EAv中的酚类化合物和黄酮类化合物。在将黑色素瘤细胞静脉注射到C57BL/6小鼠后,EAv显著抑制了肺黑色素瘤的发展。脾脏横截面的体视学分析显示,EAv处理后红髓区域增大,这表明造血系统被激活。用EAv治疗荷黑色素瘤小鼠不会导致肝损伤。总之,这些发现表明天鹅绒雅典娜是具有强大抗转移活性的天然产物来源。