RESUMEN
Recent studies exhibit that 4-hydroxyphenylretinamide (4HPR) decreases aromatase activity in breast and placental cells. The effect of synthetic 4HPR analogs on aromatase and expression was examined in three breast cancer cell lines. Most derivatives did not decrease cellular aromatase activity. Two of the analogs even stimulated aromatase activity at the transcriptional level. Only one derivative significantly decreased aromatase in all three breast cancer cell lines and also suppressed CYP19 gene expression in one of the cell line. Placental microsomal aromatase assay rule out the possibility that this compound directly inhibits the aromatase enzyme. A non-genomic mechanism in suppression of cellular aromatase activity of this compound is proposed.
Asunto(s)
Inhibidores de la Aromatasa/farmacología , Aromatasa/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/enzimología , Fenretinida/análogos & derivados , Antineoplásicos/química , Antineoplásicos/farmacología , Aromatasa/genética , Inhibidores de la Aromatasa/química , Secuencia de Bases , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Cartilla de ADN/genética , Femenino , Fenretinida/química , Fenretinida/farmacología , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Microsomas/efectos de los fármacos , Microsomas/enzimología , Placenta/enzimología , Embarazo , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismoRESUMEN
Using solid phase-assisted synthesis and purification, a 49 member library of analogs of the mammary tumor chemopreventive retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) has been prepared. After prescreening for growth inhibitory activity in human mammary tumor cells (MCF-7) in culture, most of those analogs which showed activity (12 of them) were assayed for apoptosis-inducing activity in the MCF-7 cells. At least 3 of the analogs (13, 24, and 28) showed activity approaching that of 4-HPR.