title: Beta-carotene and apocarotenals promote retinoid signaling in BEAS-2B human bronchioepithelial cells.
abstract: High dose beta-carotene supplementation of smokers was associated with increased lung cancer risk in two intervention trials. It was proposed that generation of apocarotenals in smoke-exposed lungs impaired retinoic acid (RA) signaling, leading to squamous metaplasia and cell proliferation. To test this, we compared RA target gene regulation by retinoids, apocarotenals or beta-carotene by transcriptomics in BEAS-2B cells cultured to promote squamous differentiation. Retinoids, beta-carotene as well as apocarotenals induced known RA target genes. Retinoids upregulated involucrin, indicating that retinoids did not rescue BEAS-2B cells from squamous differentiation. Muc5AC, a marker for mucous differentiation, was transiently induced. beta-Carotene and apocarotenals less strongly induced involucrin and did not induce muc5AC. In summary, apocarotenals or beta-carotene upregulated RA target genes suggesting promotion, not inhibition, of RA signaling in BEAS-2B cells. Furthermore, apocarotenals and beta-carotene regulated gene expression independently of RA signaling. Squamous differentiation is not unequivocally linked to RA deficiency in BEAS-2B cells.
authors.affiliation: DSM Nutritional Products, R&D, Human Nutrition and Health, P. O. Box 3255, CH-4002 Basel, Switzerland.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Kuntz
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hoeller
authors.forename: Brad
authors.initials: B
authors.lastname: Greatrix
authors.forename: Christopher
authors.initials: C
authors.lastname: Lankin
authors.forename: Nicole
authors.initials: N
authors.lastname: Seifert
authors.forename: Samir
authors.initials: S
authors.lastname: Acharya
authors.forename: Georges
authors.initials: G
authors.lastname: Riss
authors.forename: Petra
authors.initials: P
authors.lastname: Buchwald-Hunziker
authors.forename: Willi
authors.initials: W
authors.lastname: Hunziker
authors.forename: Regina
authors.initials: R
authors.lastname: Goralczyk
authors.forename: Karin
authors.initials: K
authors.lastname: Wertz
mesh_terms: D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002338:Carotenoids / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D016000:Cluster Analysis; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012176:Retinoids / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D019207:beta Carotene / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D012333:RNA, Messenger; D012176:Retinoids; D019207:beta Carotene; D002338:Carotenoids; C004984:apocarotenal