RESUMEN
Pomegranate (Punica granatum) seed linolenic acid isomers were evaluated as selective estrogen receptor modulators (SERMs) in vitro. Punicic acid (PA) inhibited (IC(50)) estrogen receptor (ER) alpha at 7.2 microM, ERbeta at 8.8 microM; alpha-eleostearic acid (AEA) inhibited ERalpha/ERbeta at 6.5/7.8 microM. PA (not AEA) agonized ERalpha/ERbeta (EC(50)) at 1.8/2 microM, antagonizing at 101/80 microM. AEA antagonized ERalpha/ERbeta at 150/140 microM. PA and AEA induced ERalpha and ERbeta mRNA expression in MCF-7, but not in MDA-MB-231. Overall, the results show PA and AEA are SERMs.
Asunto(s)
Ácidos Linoleicos/farmacología , Lythraceae/química , Fitoestrógenos/farmacología , Receptores de Estrógenos/efectos de los fármacos , Receptores de Estrógenos/fisiología , Semillas/química , Neoplasias de la Mama , División Celular/efectos de los fármacos , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/metabolismo , Receptor beta de Estrógeno/genética , Receptor beta de Estrógeno/metabolismo , Ácidos Grasos/análisis , Humanos , Isomerismo , Ácidos Linoleicos/química , Ácidos Linoleicos/metabolismo , Ácidos Linoleicos Conjugados/metabolismo , Ácidos Linolénicos/metabolismo , Fitoestrógenos/metabolismo , Aceites de Plantas/química , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Moduladores Selectivos de los Receptores de Estrógeno/metabolismo , Moduladores Selectivos de los Receptores de Estrógeno/farmacologíaRESUMEN
The CKII inhibitory compound was purified from the fruit of Xanthium strumarium by organic solvent extraction and silica gel chromatography. The inhibitory compound was identified as 3,4-dihydroxybenzaldehyde by analysis with FT-IR, FAB-Mass, EI-Mass, (1)H-NMR and (13)C-NMR. 3,4-dihydroxybenzaldehyde inhibited the phosphotransferase activity of CKII with IC(50) of about 783 microM. Steady-state studies revealed that the inhibitor acts as a competitive inhibitor with respect to the substrate ATP. A value of 138.6 microM was obtained for the apparent K(i). Concentration of 300 microM 3,4-dihydroxybenzaldehyde caused 50% growth inhibition of human cancer cell U937. 3,4-dihydroxybenzaldehyde-induced cell death was characterised with the cleavage of poly(ADP-ribose) polymerase and procaspase-3. Furthermore, the inhibitor induced the fragmentation of DNA into multiples of 180 bp, indicating that it triggered apoptosis. This induction of apoptosis by 3,4-dihydroxybenzaldehyde was also confirmed by using flow cytometry analysis. Since CKII is involved in cell proliferation and oncogenesis, these results suggest that 3,4-dihydroxybenzaldehyde may function by inhibiting oncogenic disease, at least in part, through the inhibition of CKII activity.