title: Aralin, a type II ribosome-inactivating protein from Aralia elata, exhibits selective anticancer activity through the processed form of a 110-kDa high-density lipoprotein-binding protein: a promising anticancer drug.
abstract: Aralin from Aralia elata is a newly identified type II ribosome- inactivating protein, which preferentially induces apoptosis in cancer cells. In this study, we identified that the aralin receptor is a 110-kDa high-density lipoprotein-binding protein (HDLBP), which functions as a HDL receptor. The sensitivities of tumor cell lines to aralin were dependent on the expression levels of the 110-kDa HDLBP and its forced expression in aralin-resistant Huh7 cells conferred aralin sensitivity. HDLBP-knockdown HeLa cells showed a significant aralin resistance in vitro and in vivo. Conversely, ectopic expression of the 150-kDa HDLBP resulted in increased aralin sensitivity in vivo, accompanying enhanced expression of the 110-kDa HDLBP. Thus, these results showed that the 110-kDa HDLBP in lipid rafts acted as an aralin receptor and that its expression levels determined aralin sensitivity, suggesting that aralin could be a promising anticancer drug for HDLBP-overexpressing tumors.
authors.affiliation: Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Tokyo 125-8585, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Otsuka
authors.affiliation: Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Tokyo 125-8585, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Gotoh
authors.affiliation: Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Tokyo 125-8585, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Komeno
authors.affiliation: Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Tokyo 125-8585, Japan.
authors.forename: Takahide
authors.initials: T
authors.lastname: Ono
authors.affiliation: Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Tokyo 125-8585, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kawasaki
authors.affiliation: Division of Biochemistry, School of Pharmaceutical Science, Kitasato University, Tokyo 108-8641, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Iida
authors.affiliation: Division of Biochemistry, School of Pharmaceutical Science, Kitasato University, Tokyo 108-8641, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Shibagaki
authors.affiliation: Division of Biochemistry, School of Pharmaceutical Science, Kitasato University, Tokyo 108-8641, Japan.
authors.forename: Seisuke
authors.initials: S
authors.lastname: Hattori
authors.affiliation: Akita Research Institute of Food and Brewing (ARIF), Akita 010-1623, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tomatsu
authors.affiliation: Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Tokyo 125-8585, Japan.
authors.forename: Hirotada
authors.initials: H
authors.lastname: Akiyama
authors.affiliation: Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Tokyo 125-8585, Japan. Electronic address: ftashir@rs.noda.tus.ac.jp.
authors.forename: Fumio
authors.initials: F
authors.lastname: Tashiro
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D027983:Aralia / Q000737:chemistry; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D008075:Lipoproteins, HDL / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism; D008819:Mice, Nude; D008970:Molecular Weight; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018110:Receptors, Lipoprotein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D054790:Ribosome Inactivating Proteins, Type 2 / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008075:Lipoproteins, HDL; D016601:RNA-Binding Proteins; D018110:Receptors, Lipoprotein; D011994:Recombinant Proteins; D054790:Ribosome Inactivating Proteins, Type 2; C488031:aralin; C031616:high density lipoprotein receptors; C075197:high density lipoprotein binding protein
keywords: Anticancer drug; Aralia elata; Aralin; High-density lipoprotein-binding protein (HDLBP); Ribosome-inactivating protein (RIP)