title: Hydroxytyrosyl ethyl ether exhibits stronger intestinal anticarcinogenic potency and effects on transcript profiles compared to hydroxytyrosol.
abstract: The anticarcinogenic activity of hydroxytyrosyl ethyl ether (HTy-Et) compared to its precursor hydroxytyrosol (HTy) has been studied in human Caco-2 colon adenocarcinoma cells. 451 and 977 genes were differentially expressed in Caco-2 cells exposed to HTy or HTy-Et for 24h, respectively, compared with untreated cells (P<0.005; FDR=0), using Affymetrix microarrays. Results showed that both HTy and HTy-Et inhibited cell proliferation and arrested the cell cycle by up-regulating p21 and CCNG2 and down-regulating CCNB1 protein expression. HTy and HTy-Et also altered the transcription of specific genes involved in apoptosis, as suggested by the up-regulation of BNIP3, BNIP3L, PDCD4 and ATF3 and the activation of caspase-3. Moreover, these polyphenols up-regulated xenobiotic metabolizing enzymes UGT1A10 and CYP1A1, enhancing carcinogen detoxification. In conclusion, these results highlight that HTy and its derivative HTy-Et modulate molecular mechanisms involved in colon cancer, with HTy-Et being more effective than HTy.
authors: Institute of Food Research, Norwich Research Park, Colney Lane, Norwich NR4 7UA, UK.
authors: G
authors: G
authors: Pereira-Caro
authors: R
authors: R
authors: Mateos
authors: M H
authors: MH
authors: Traka
authors: J R
authors: JR
authors: Bacon
authors: R
authors: R
authors: Bongaerts
authors: B
authors: B
authors: Sarriá
authors: L
authors: L
authors: Bravo
authors: P A
authors: PA
authors: Kroon
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D018938:Caco-2 Cells; D002396:Catechols / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D059467:Transcriptome / Q000187:drug effects
chemical_list: D016588:Anticarcinogenic Agents; D002396:Catechols; C000605802:ethyl hydroxytyrosyl ether; C005975:3,4-dihydroxyphenylethanol; D010626:Phenylethyl Alcohol