RESUMEN
Two new sesquiterpenes deltoiden A (1) and deltoiden B (2), and two new lignans deltoignan A (9) and deltoignan B (10), together with 14 known compounds, including six sesquiterpenes 3-8 and three lignans 11-13, were isolated from the whole plant of Saussurea deltoidea. Compounds 3-8 and 11-17 were isolated for the first time from this plant. Their structures were established by spectroscopic analysis, including 2D-NMR spectroscopic techniques. Cytotoxicities of compounds 1-13 were tested against three cancer cell lines A549, Hela and SMMC-7721. Results showed that 5, 6 and 7 exhibited cytotoxicity against SMMC-7721 with the IC(50) values of 6.49, 9.53, 1.23 µg/ml, 5 and 7 against A549 with the IC(50) values of 4.99 and 5.35 µg/ml, 5, 6, 7, 13 against Hela with the IC(50) values of 1.40, 4.75, 0.93 and 5.42 µg/ml, respectively. The structure-activity relationships of sesquiterpenes 1-8 were discussed on the base of cytotoxic results.
Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Lignanos/uso terapéutico , Neoplasias/tratamiento farmacológico , Fitoterapia , Extractos Vegetales/uso terapéutico , Saussurea/química , Sesquiterpenos/uso terapéutico , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Células HeLa , Humanos , Concentración 50 Inhibidora , Lignanos/aislamiento & purificación , Lignanos/farmacología , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/farmacología , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos/farmacología , Relación Estructura-ActividadRESUMEN
Inula helianthus-aquatica C. Y. Wu is a traditional medicinal plant used to treat some cancers in folk herbal medicine of Yunnan, China. Bigelovin, a sesquiterpene lactone isolated from this herb, potently inhibits the growth of a panel of eight cancer cell lines, especially in human monoblastic leukemia U937 cells with an IC(50) value of 0.47 microM. Characteristic morphological features of apoptosis were observed in U937 cells treated with bigelovin. Annexin V and nuclear DNA content distribution assays showed that the percentage of Annexin V positive cells increased to 8.86% (24 h) with 1 microM bigelovin treatment, and cells treated with bigelovin at this concentration apparently arrested at G(0)/G(1) phase compared with the control. These data suggested that cytotoxic effect of bigelovin on U937 cells involves induction of apoptosis, and the cell cycle is arrested at G(0)/G(1) phase.
Asunto(s)
Apoptosis/efectos de los fármacos , Inula/química , Lactonas/farmacología , Sesquiterpenos/farmacología , Anexina A5 , Antineoplásicos Fitogénicos/farmacología , Ciclo Celular/efectos de los fármacos , Proliferación Celular , Medicamentos Herbarios Chinos/farmacología , Humanos , Células U937RESUMEN
DNA Topoisomerase I can cause DNA breaks and play a key role during cell proliferation and differentiation. It is an important target for anticancer agents. While screening for anticancer compounds, seven natural compounds, 1-7, showed potent cytotoxicities against a panel of ten cancer cell lines. Moreover, an inhibition assay demonstrated that they are also DNA topoisomerase I inhibitors, in which inhibitors 1-5 are new ones.
