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Effects of Retinoids at the Cellular Level (Differentiation, Apoptosis, Autophagy, Cell Cycle Regulation, and Senescence)
Published in Ayse Serap Karadag, Berna Aksoy, Lawrence Charles Parish, Retinoids in Dermatology, 2019
The entry of RA into the nucleus, where binding to receptors occurs, depends upon the retinoid binding proteins. These cytosolic proteins include cellular retinol-binding proteins (RBP): RBP1, RBP2, cellular retinoic acid-binding protein 1 and 2 (CRABP1, CRABP2), and fatty acid-binding protein 5 (FABP5), which are responsible for cellular transport of poorly soluble retinoids during uptake, metabolism, and function (5).
All-trans retinoic acid in anticancer therapy: how nanotechnology can enhance its efficacy and resolve its drawbacks
Published in Expert Opinion on Drug Delivery, 2021
Gabriel Silva Marques Borges, Flávia Alves Lima, Guilherme Carneiro, Gisele Assis Castro Goulart, Lucas Antônio Miranda Ferreira
Altered catabolism by the CYP enzymes and ATRA sequestration by the cellular retinoic acid binding proteins (CRABP) are among the reasons listed for these bioavailability issues during the treatment [86]. CRABP1 and CRABP2 are proteins that can bind ATRA with high affinity and allow transportation of the hydrophobic ATRA in the aqueous cellular milieu. CRABP2 transport ATRA from the cytoplasm to the nucleus, allowing its binding to RAR. CRABP1 is related to ATRA catabolism, directing it to CYP enzymes. Several cancer cells less sensitive to ATRA, had enhanced expression of CRABP1 [87–90]. ATRA is metabolized by the CYP enzymes into a variety of polar metabolites and the main metabolism pathway is the 4-hydroxilation. Among the CYP enzymes, CYP26 seems to be to most specific for ATRA, and the subtypes CYP26A1 and CYP26B2 are the most studied ones. Many cancer types, including breast, colorectal, ovarian, and head and neck cancers show increased expression of CYP26 enzymes [87,91].