RESUMO
Phytochemical investigation of the seeds of Thevetia peruviana resulted in the isolation of seven cardiac glycosides (1-7), including two new compounds (1 and 2). Cytotoxicity of them toward cancer cell lines P15 (human lung cancer cell), MGC-803 (human gastric cancer cells), SW1990 (human pancreatic cancer cells), and normal hepatocyte cell LO2 suggested that compound 1 could selectively inhibit the proliferation of cancer cell lines with IC50 from 0.05 to 0.15 µM. Pro-apoptotic activity revealed that it induced the apoptosis of MGC-803 cancer cells in a dose-dependent manner. Meanwhile, treatment of MGC-803 cancer cells with 1 resulted in diminution of pro-caspases 3 and 9 and activation of caspases 3 and 9, while it increased the Bax/Bcl-2 ratio in a dose-dependent manner. These meant that 1 induced the apoptosis of cancer cells by involving the intrinsic apoptotic pathway. In addition, the cell cycle distribution of MGC-803 cancer cells treated by 1 revealed that it could lead to cell cycle arrest at the G2/M phase. Altogether, this study suggested that compound 1 may exhibit anticancer activity by its capability of induction of intrinsic apoptosis and cell cycle arrest at G2/M phase.
Assuntos
Glicosídeos Cardíacos/isolamento & purificação , Glicosídeos Cardíacos/farmacologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Sementes/química , Thevetia/química , Glicosídeos Cardíacos/química , Caspase 3/metabolismo , Caspases/metabolismo , Ciclo Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Humanos , Estrutura Molecular , Ressonância Magnética Nuclear BiomolecularRESUMO
Investigation of the seeds of Thevetia peruviana resulted in the isolation of 15 new (2-16) and 18 known (1 and 17-33) cardiac glycosides. Eight 19-nor-cardenolides (1-8), including two rare 19-nor-10-hydroperoxycardenolides, were obtained from T. peruviana for the first time. All the structures were characterized by NMR spectroscopy and chemical derivatization. The inhibitory effects of cardiac glycosides 1-33 against three cancer cell lines (human lung cancer cells, P15; human gastric cancer cells, MGC-803; and human pancreatic cancer cells, SW1990) and one normal hepatocyte cell line, LO2, were evaluated, and a preliminary structure-activity relationship is discussed. In addition, cardiac glycosides 1, 22, 26, and 28 were evaluated for their apoptosis-inducing activities in MGC-803 cells, showing IC50 values in the range 0.02-0.53 µM.