title: Retinoid metabolism and all-trans retinoic acid-induced growth inhibition in head and neck squamous cell carcinoma cell lines.
abstract: Retinoids can reverse potentially premalignant lesions and prevent second primary tumours in patients with head and neck squamous cell carcinoma (HNSCC). Furthermore, it has been reported that acquired resistance to all-trans retinoic acid (RA) in leukaemia is associated with decreased plasma peak levels, probably the result of enhanced retinoid metabolism. The aim of this study was to investigate the metabolism of retinoids and relate this to growth inhibition in HNSCC. Three HNSCC cell lines were selected on the basis of a large variation in the all-trans RA-induced growth inhibition. Cells were exposed to 9.5 nM (radioactive) for 4 and 24 h, and to 1 and 10 microM (nonradioactive) all-trans RA for 4, 24, 48 and 72 h, and medium and cells were analysed for retinoid metabolites. At all concentrations studied, the amount of growth inhibition was proportional to the extent at which all-trans-, 13- and 9-cis RA disappeared from the medium as well as from the cells. This turnover process coincided with the formation of a group of as yet unidentified polar retinoid metabolites. The level of mRNA of cellular RA-binding protein II (CRABP-II), involved in retinoid homeostasis, was inversely proportional to growth inhibition. These findings indicate that for HNSCC retinoid metabolism may be associated with growth inhibition.
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: B J
authors.initials: BJ
authors.lastname: Braakhuis
authors.forename: I
authors.initials: I
authors.lastname: Klaassen
authors.forename: B M
authors.initials: BM
authors.lastname: van der Leede
authors.forename: J
authors.initials: J
authors.lastname: Cloos
authors.forename: R H
authors.initials: RH
authors.lastname: Brakenhoff
authors.forename: M P
authors.initials: MP
authors.lastname: Copper
authors.forename: T
authors.initials: T
authors.lastname: Teerlink
authors.forename: H F
authors.initials: HF
authors.lastname: Hendriks
authors.forename: P T
authors.initials: PT
authors.lastname: van der Saag
authors.forename: G B
authors.initials: GB
authors.lastname: Snow
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003470:Culture Media / Q000737:chemistry; D006258:Head and Neck Neoplasms / Q000378:metabolism*; D006801:Humans; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis; D012176:Retinoids / Q000378:metabolism*; D014212:Tretinoin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D003470:Culture Media; D018168:Receptors, Retinoic Acid; D012176:Retinoids; C082927:retinoic acid binding protein I, cellular; C082928:retinoic acid binding protein II, cellular; C002202:4-oxoretinoic acid; D014212:Tretinoin