title: Chemoprevention of Colorectal Cancer by Artocarpin, a Dietary Phytochemical from Artocarpus heterophyllus.
abstract: Artocarpus heterophyllus is an evergreen tree distributed in tropical regions, and its fruit (jackfruit) is well-known as the world's largest tree-borne fruit. Although A. heterophyllus has been widely used in folk medicines against inflammation, its potential in cancer chemoprevention remains unclear. Herein we identified artocarpin from A. heterophyllus as a promising colorectal cancer chemopreventive agent by targeting Akt kinase. Phenotypically, artocarpin exhibited selective cytotoxicity against human colon cancer cells. Artocarpin impaired the anchorage-independent growth capability, suppressed colon cancer cell growth, and induced a G1 phase cell cycle arrest which was followed by apoptotic as well as autophagic cell death. Mechanistic studies revealed that artocarpin directly targeted Akt 1 and 2 kinase activity evidenced by in vitro kinase assay, ex vivo binding assay as well as Akt downstream cellular signal transduction. Importantly, oral administration of artocarpin attenuated colitis-associated colorectal tumorigenesis in mice. Taken together, artocarpin, a bioactive component of A. heterophyllus, might merit investigation as a potential colorectal cancer chemopreventive agent.
authors.affiliation: School of Food Science and Technology, Jiangnan University , Wuxi 214122, China.
authors.forename: Guochuan
authors.initials: G
authors.lastname: Sun
authors.affiliation: School of Food Science and Technology, Jiangnan University , Wuxi 214122, China.
authors.forename: Zongping
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: The Hormel Institute, University of Minnesota , Austin 55912, United States.
authors.forename: Mee-Hyun
authors.initials: MH
authors.lastname: Lee
authors.affiliation: School of Food Science and Technology, Jiangnan University , Wuxi 214122, China.
authors.forename: Yijuan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: The Hormel Institute, University of Minnesota , Austin 55912, United States.
authors.forename: Soouk
authors.initials: S
authors.lastname: Kang
authors.affiliation: The Hormel Institute, University of Minnesota , Austin 55912, United States.
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
authors.affiliation: School of Biological Sciences, The University of Hong Kong , Hong Kong, China.
authors.forename: Mingfu
authors.initials: M
authors.lastname: Wang
authors.affiliation: School of Food Science and Technology, Jiangnan University , Wuxi 214122, China.
authors.forename: Zhennan
authors.initials: Z
authors.lastname: Gu
authors.affiliation: School of Food Science and Technology, Jiangnan University , Wuxi 214122, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Li
authors.affiliation: School of Food Science and Technology, Jiangnan University , Wuxi 214122, China.|Beijing Innovation Centre of Food Nutrition and Human Health, Beijing Technology & Business University , Beijing 100048, China.
authors.forename: Wei
authors.identifier: http://orcid.org/0000-0003-3348-4710
authors.initials: W
authors.lastname: Chen
mesh_terms: D000818:Animals; D031622:Artocarpus / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D008297:Male; D037241:Mannose-Binding Lectins / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D064209:Phytochemicals / Q000008:administration & dosage*; D010936:Plant Extracts / Q000008:administration & dosage*; D037121:Plant Lectins / Q000008:administration & dosage*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism
chemical_list: D037241:Mannose-Binding Lectins; D064209:Phytochemicals; D010936:Plant Extracts; D037121:Plant Lectins; C090683:artocarpin lectin; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt; Artocarpus heterophyllus; artocarpin; colorectal cancer