Influence of isomerisation on the growth inhibitory effects and cellular activity of 13-cis and all-trans retinoic acid in neuroblastoma cells.

摘要: Treatment with 13-cis retinoic acid (13-cis RA) has been shown to significantly improve the clinical outcome of children high-risk neuroblastoma. Despite large number studies investigating cellular effects retinoids in neuroblastoma cells, influence RA isomerisation and factors that determine extent uptake are unknown. The aim this study was establish extra- intracellular all-trans (ATRA) cell lines, investigate on their growth inhibitory regulation expression binding protein II (CRABP II) RAR-beta. Limited extracellular observed up 72 hr after incubation four lines 10 microM or ATRA. isomer present initially medium accounted for >75% retinoid exposure. By contrast, resulted levels ATRA comparable those RA. This degree not incubations, accounting <10% total retinoids. No differences were sensitivity three N-type either (IC(50): 11.2-13.9 microM) 12.9-14.4 microM), despite 10-fold levels. A decrease (IC(50)=137 as compared (IC(50)=41 S-type line SH S EP. RAR-beta induced a dose-dependent manner SY 5Y cells following ATRA, whereas weaker delayed induction Similarly, greater CRABP these cells. In summary, results indicate an conversion selective suggest may mediate differential activity subtypes.