Induction of the oxidative catabolism of retinoid acid in MCF-7 cells
| Autor: | J. Van Dun, Lieve Dillen, M. D. W. G. Krekels, A. Verhoeven, W. Wouters, C. Van Hove, M.-C. Coene, W. Cools |
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| Jazyk: | angličtina |
| Rok vydání: | 1997 |
| Předmět: |
Cancer Research
Antineoplastic Agents Hormonal medicine.drug_class Retinoic acid Breast Neoplasms Tretinoin Oxidative phosphorylation Biology chemistry.chemical_compound Retinoids Cytosol Keratolytic Agents medicine Tumor Cells Cultured Humans Retinoid Catabolism Retinol Imidazoles Reproducibility of Results Retinol-Binding Proteins Retinol binding protein Retinoic acid receptor Oncology chemistry Biochemistry Female Oxidation-Reduction medicine.drug Research Article |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | Cytochrome P450-dependent oxidation is a pathway for all-trans-retinoic acid (all-trans-RA) catabolism. Induction of this catabolic pathway was studied in MCF-7 breast cancer cells. MCF-7 cells showed low constitutive all-trans-RA catabolism. Concentration-dependent induction was obtained by preincubation of the cells with all-trans-RA (10(-9) to 10(-6) M). Onset of induction was fast, being detectable within 60 min, with maximal induction (45-fold) obtained after 16 h. Enzymatic characterization of induced all-trans-RA catabolism showed an estimated Km value (Michaelis-Menten constant) of 0.33 microM and a Vmax value (maximal velocity of an enzyme-catalysed reaction) of 54.5 fmol polar all-trans-RA metabolites 10(6) cells(-1) h(-1). These kinetic parameters represent the overall formation of polar metabolites from all-trans-RA. Induction of all-trans-RA catabolism was also obtained with other retinoids, CH55 >> 13-cis-RA = all-trans-RA > 9-cis-RA > 4-keto-all-trans-RA > 4-keto-13-cis-RA > retinol. The potency of the retinoids to induce all-trans-RA catabolism was correlated to their retinoic acid receptor affinity (Crettaz et al, 1990; Repa et al, 1990; Sani et al, 1990). Induction of all-trans-RA catabolism was inhibited by actinomycin D. Furthermore, all-trans-RA did not increase cytosolic retinoic acid-binding protein (CRABP) mRNA levels. These data suggest that induction of all-trans-RA catabolism in MCF-7 cells is a retinoic acid receptor-mediated gene transcriptional event. Induced all-trans-RA catabolism was inhibited by various retinoids with decreasing potency in the order: all-trans-RA > 4-keto-all-trans-RA > 13-cis-RA > 9-cis-RA > 4-keto-13-cis-RA > retinol > CH55. The antitumoral compound liarozole-fumarate inhibited all-trans-RA catabolism with a potency similar to that of all-trans-RA. Images Figure 4 |
| Databáze: | OpenAIRE |
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