title: Furospinosulin-1, Marine Spongean Furanosesterterpene, Suppresses the Growth of Hypoxia-Adapted Cancer Cells by Binding to Transcriptional Regulators p54(nrb) and LEDGF/p75.
abstract: Hypoxia-adapted cancer cells in tumors contribute to the pathological progression of cancer. Cancer research has therefore focused on the identification of molecules responsible for hypoxia adaptation in cancer cells, as well as the development of new compounds with action against hypoxia-adapted cancer cells. The marine natural product furospinosulin-1 (1) has displayed hypoxia-selective growth inhibition against cultured cancer cells, and has shown in vivo anti-tumor activity, although its precise mode of action and molecular targets remain unclear. In this study, we found that 1 is selectively effective against hypoxic regions of tumors, and that it directly binds to the transcriptional regulators p54(nrb) and LEDGF/p75, which have not been previously identified as mediators of hypoxia adaptation in cancer cells.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka, 565-0871, Japan. araim@phs.osaka-u.ac.jp.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Arai
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka, 565-0871, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kawachi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka, 565-0871, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kotoku
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka, 565-0871, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Nakata
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka, 565-0871, Japan.|National Institute of Biomedical Innovation, 7-6-8 Saitoasagi, Ibaraki, Osaka, 567-0085, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Kamada
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka, 565-0871, Japan.|National Institute of Biomedical Innovation, 7-6-8 Saitoasagi, Ibaraki, Osaka, 567-0085, Japan.
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Tsunoda
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka, 565-0871, Japan.|National Institute of Biomedical Innovation, 7-6-8 Saitoasagi, Ibaraki, Osaka, 567-0085, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Tsutsumi
authors.affiliation: Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka, 537-8511, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Endo
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka, 565-0871, Japan.|Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka, 537-8511, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Inoue
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka, 565-0871, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sato
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka, 565-0871, Japan. kobayasi@phs.osaka-u.ac.jp.
authors.forename: Motomasa
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D015687:Cell Hypoxia / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use; D004268:DNA-Binding Proteins; D005455:Fluorescent Antibody Technique; D055785:Gene Knockdown Techniques; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000235:genetics; D051379:Mice; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy; D034521:Nuclear Matrix-Associated Proteins / Q000737:chemistry*; D050810:Octamer Transcription Factors / Q000737:chemistry*; D011485:Protein Binding / Q000187:drug effects; D016601:RNA-Binding Proteins / Q000737:chemistry*; D054830:Sesterterpenes / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D004268:DNA-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C083214:NONO protein, human; D034521:Nuclear Matrix-Associated Proteins; D050810:Octamer Transcription Factors; D016601:RNA-Binding Proteins; D054830:Sesterterpenes; C555679:furospinosulin-1; C119380:lens epithelium-derived growth factor; D002945:Cisplatin
keywords: anticancer agents; binding protein; cancer; furospinosulin-1; hypoxia; natural products