Hydroxytyrosyl ethyl ether exhibits stronger intestinal anticarcinogenic potency and effects on transcript profiles compared to hydroxytyrosol

• Published in: Food chemistry Vol. 138; no. 2-3; pp. 1172 - 1182
• Main Authors: Pereira-Caro, G., Mateos, R., Traka, M.H., Bacon, J.R., Bongaerts, R., Sarriá, B., Bravo, L., Kroon, P.A.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.06.2013; Elsevier
• Subjects: Anticarcinogenic Agents - pharmacology; Apoptosis - drug effects; Biological and medical sciences; Caco-2 Cells; Catechols - pharmacology; Cell Cycle Checkpoints - drug effects; Colonic Neoplasms - drug therapy; Colonic Neoplasms - genetics; Colonic Neoplasms - metabolism; Fat industries; Food industries; Fundamental and applied biological sciences. Psychology; Gene expression; Humans; Hydroxytyrosol; Hydroxytyrosyl ethers; Intestines - drug effects; Intestines - metabolism; Microarrays; Phenylethyl Alcohol - analogs & derivatives; Phenylethyl Alcohol - pharmacology; Transcriptome - drug effects; Transcriptome analysis; Virgin olive oil phenols; Hydroxytyrosol; Transcriptome analysis; Caco-2 cells; Virgin olive oil phenols; Microarrays; Hydroxytyrosyl ethers; Gene expression; Ether; Digestive system; Gut; Vegetable oil; Olive oil; Edible oil; Profile; Virgin oil; Phenol; Messenger RNA; Analysis; Phenols; Comparative study
• ISSN: 0308-8146; 1873-7072
• DOI: 10.1016/j.foodchem.2012.11.118

► Hydroxytyrosol and hydroxytyrosyl ethyl ether alter genes related with colon cancer prevention in a dose dependent manner. ► Both polyphenols arrest cell cycle, induce apoptosis and enhance carcinogen detoxification. ► Hydroxytyrosyl ethyl ether shows more anticarcinogenic colorectal activity than its precursor, hydroxytyrosol. 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.