RESUMEN
In a previous study, we isolated thyrsiflorin A, a new diterpene with the scopadulane skeleton, from Calceolaria thyrsiflora (Scrophulariaceae family). Experimental evidences on the semisynthetic analogues of scopadulane diterpenes have permitted to hypothesize that a polar substituent is important for the antitumor activity of this class of compounds. Therefore, the present study was undertaken to investigate the effect of the semisynthetic compound, demalonyl thyrsiflorin A, on cell growth and death in two human epithelial cell lines, DU-145 cells (androgen-insensitive prostate cancer cells) and KB cells (oral squamous carcinoma cells). The results obtained, show that our compound, exhibited comparable degrees of antigrowth effect on cancer cells examined as judged by IC(50) values, 9.77 microM (2.73 microg/ml) and 10.86 microM (3.04 microg/ml) in DU-145 and KB cells, respectively, and support the hypothesis that also for diterpenoid compounds an available hydroxyl group is important for decreased cancer cell viability. In addition, we demonstrated an apoptotic response after treatment of DU-145 and KB cells with this semisynthetic compound at 6-12 microM concentrations, together with a necrosis process at higher doses (25-50 microM). Both apoptotic and necrotic pathway implicated in demalonyl thyrsiflorin A-treated cells are correlated with the elevation of ROS generation.
Asunto(s)
Apoptosis/efectos de los fármacos , Diterpenos/toxicidad , Células Epiteliales/efectos de los fármacos , Células Epiteliales/patología , Neoplasias/inducido químicamente , Neoplasias/parasitología , Caspasa 3/metabolismo , Línea Celular Tumoral , Diterpenos/síntesis química , Diterpenos/química , Células Epiteliales/metabolismo , Genoma Humano/genética , Humanos , Hidroliasas/metabolismo , Estructura Molecular , Necrosis/inducido químicamente , Necrosis/patología , Neoplasias/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Chemical examination of the petrol ether (60-80) extract of the aerial parts of Calceolaria alba R. et Pav., collected in Santa Juana, VIII Region, Chile, resulted in the isolation of 3 new diterpenoids. Their structures have been elucidated by a study of their physical and spectral data; in particular using 2 NMR spectroscopy (DEPT, 1H-1H, COSY, NOESY, HMQC and HMBC).
Asunto(s)
Diterpenos/química , Scrophulariaceae/química , Diterpenos/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificaciónRESUMEN
The crude methanolic root extract of Myoschilos oblongum exhibited a significant cytotoxic activity against PZ-HPV-7 human prostate cells. Furthermore, two esters of docosanol were isolated from the CH(2)Cl(2) extract.