title: Dietary ω-3 Polyunsaturated Fatty Acids Inhibit Tumor Growth in Transgenic ApcMin/+Mice, Correlating with CB1 Receptor Up-Regulation.
abstract: Mediterranean diet components, such as olive oil and ω-3 polyunsaturated fatty acids (ω-3 PUFAs), can arrest cell growth and promote cell apoptosis. Recently, olive oil has been demonstrated to modulate type-1 cannabinoid (CB1) receptor gene expression in both human colon cancer cells and rat colon. The aim of this study was to investigate a possible link between olive oil and ω-3 PUFAs effects and CB1 receptor expression in both intestinal and adipose tissue of ApcMin/+mice. To confirm the role for the CB1 receptor as a negative modulator of cell proliferation in human colon cancer,CB1receptor gene expression was also detected in tumor tissue and in surrounding normal mucosa of patients with colorectal cancer (CRC). Dietary ω-3 PUFAs significantly inhibited intestinal polyp growth in mice, correlating withCB1receptor gene and protein expression induction.CB1receptor gene up-regulation was also detected in adipose tissue, suggesting a close communication between cancer cells and the surrounding environment. Tissue CB1 receptor induction was associated with a concurrent inactivation of the Wnt/β-catenin pathway. Moreover, there was a significant reduction inCB1receptor gene expression levels in cancer tissue compared to normal surrounding mucosa of patients with CRC, confirming that in cancer the "protective" action of the CB1 receptor is lost.
authors.affiliation: National Institute of Gastroenterology "S. de Bellis", Research Hospital, Castellana Grotte, Bari 70013, Italy. maria.notarnicola@irccsdebellis.it.
authors.forename: Maria
authors.initials: M
authors.lastname: Notarnicola
authors.affiliation: National Institute of Gastroenterology "S. de Bellis", Research Hospital, Castellana Grotte, Bari 70013, Italy. valeria.tutino@irccsdebellis.it.
authors.forename: Valeria
authors.initials: V
authors.lastname: Tutino
authors.affiliation: National Institute of Gastroenterology "S. de Bellis", Research Hospital, Castellana Grotte, Bari 70013, Italy. valentinadx@hotmail.it.
authors.forename: Valentina
authors.initials: V
authors.lastname: De Nunzio
authors.affiliation: National Institute of Gastroenterology "S. de Bellis", Research Hospital, Castellana Grotte, Bari 70013, Italy. francesco.dituri@irccsdebellis.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Dituri
authors.affiliation: National Institute of Gastroenterology "S. de Bellis", Research Hospital, Castellana Grotte, Bari 70013, Italy. gabriella.caruso@irccsdebellis.it.
authors.forename: Maria Gabriella
authors.initials: MG
authors.lastname: Caruso
authors.affiliation: National Institute of Gastroenterology "S. de Bellis", Research Hospital, Castellana Grotte, Bari 70013, Italy. gianluigi.giannelli@irccsdebellis.it.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Giannelli
mesh_terms: D000821:Animal Feed; D000818:Animals; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000378:metabolism*; D015870:Gene Expression; D017491:Genes, APC; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D015525:Fatty Acids, Omega-3; D043884:Receptor, Cannabinoid, CB1
keywords: CB1 receptor; colon cancer; olive oil; transgenic ApcMin/+ mice; ω-3 polyunsaturated fatty acids