title: Antitumor effects of saffron-derived carotenoids in prostate cancer cell models.
abstract: Crocus sativus L. extracts (saffron) are rich in carotenoids. Preclinical studies have shown that dietary intake of carotenoids has antitumor effects suggesting their potential preventive and/or therapeutic roles. We have recently reported that saffron (SE) and crocin (CR) exhibit anticancer activity by promoting cell cycle arrest in prostate cancer (PCa) cells. It has also been demonstrated that crocetin esters are produced after SE gastrointestinal digestion by CR hydrolysis. The aim of the present report was to investigate if SE, crocetin (CCT), and CR affected in vivo tumor growth of two aggressive PCa cell lines (PC3 and 22rv1) which were xenografted in male nude mice treated by oral gavage with SE, CR, and CCT. We demonstrated that the antitumor effects of CCT were higher when compared to CR and SE and treatments reverted the epithelial-mesenchymal transdifferentiation (EMT) as attested by the significant reduction of N-cadherin and beta-catenin expression and the increased expression of E-cadherin. Additionally, SE, CR, and CCT inhibited PCa cell invasion and migration through the downmodulation of metalloproteinase and urokinase expression/activity suggesting that these agents may affect metastatic processes. Our findings suggest that CR and CCT may be dietary phytochemicals with potential antitumor effects in biologically aggressive PCa cells.
authors.affiliation: Laboratory of Radiobiology, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, 67100 L'Aquila, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Festuccia
authors.affiliation: Laboratory of Radiobiology, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, 67100 L'Aquila, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mancini
authors.affiliation: Laboratory of Radiobiology, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, 67100 L'Aquila, Italy ; Section of Medical Pathophysiology, Food Science and Endocrinology, Department of Experimental Medicine, University of Rome "La Sapienza", 00161 Rome, Italy.
authors.forename: Giovanni Luca
authors.initials: GL
authors.lastname: Gravina
authors.affiliation: Laboratory of Radiobiology, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, 67100 L'Aquila, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Scarsella
authors.affiliation: Area of Physiology, Department of Medical Sciences, School of Medicine and Regional Centre for Biomedical Research (CRIB), University of Castilla-La Mancha, 02006 Albacete, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Llorens
authors.affiliation: Cátedra Química Agricola, Universidad de Castilla-La Mancha, Avenida de España s/n., 02071 Albacete, Spain.
authors.forename: Gonzalo L
authors.initials: GL
authors.lastname: Alonso
authors.affiliation: Department of Health Sciences, University of L'Aquila, 67100 L'Aquila, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Tatone
authors.affiliation: Department of Biotechnological and Applied Clinical Sciences, Division of Radiotherapy, San Salvatore Hospital, University of L'Aquila, 67100 L'Aquila, Italy.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Di Cesare
authors.affiliation: Department of Clinical and Applied Sciences and Biotechnologies, School of Sexology, University of L'Aquila, 67100 L'Aquila, Italy.
authors.forename: Emmanuele A
authors.initials: EA
authors.lastname: Jannini
authors.affiliation: Section of Medical Pathophysiology, Food Science and Endocrinology, Department of Experimental Medicine, University of Rome "La Sapienza", 00161 Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Lenzi
authors.affiliation: Department of Biotechnological and Applied Clinical Sciences, Division of Radiotherapy, San Salvatore Hospital, University of L'Aquila, 67100 L'Aquila, Italy.
authors.forename: Anna M
authors.initials: AM
authors.lastname: D'Alessandro
authors.affiliation: Cátedra Química Agricola, Universidad de Castilla-La Mancha, Avenida de España s/n., 02071 Albacete, Spain ; Albacete Science and Technology Park, Avenida de la Innovacion, 02006 Albacete, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Carmona
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D015820:Cadherins / Q000378:metabolism; D002338:Carotenoids / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D054338:Cell Transdifferentiation / Q000187:drug effects; D027622:Crocus / Q000737:chemistry*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D014801:Vitamin A / Q000031:analogs & derivatives; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D015820:Cadherins; D010936:Plant Extracts; D051176:beta Catenin; C487773:trans-sodium crocetinate; D014801:Vitamin A; D002338:Carotenoids; C029036:crocin