title: Hedgehog inhibitors from Artocarpus communis and Hyptis suaveolens.
abstract: The hedgehog (Hh) signaling pathway plays crucial roles in cell maintenance and proliferation during embryonic development. Naturally occurring Hh inhibitors were isolated from Artocarpus communis and Hyptis suaveolens using our previously constructed cell-based assay system. Bioactivity guided fractionation led to the isolation of 15 compounds, including seven new compounds (4, 5, 6, 7, and 9-11). The isolated compounds showed cytotoxicity against a cancer cell line (PANC1) in which Hh signaling was abnormally activated. Several compounds (12-14; GLI1 transcriptional inhibition IC50=7.6, 4.7, and 4.0 μM, respectively) inhibited Hh related protein (BCL2) expression. Moreover, compounds 1, 12, and 13 disrupted GLI1 and DNA complex formation.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan. Electronic address: midori_arai@chiba-u.jp.
authors.forename: Midori A
authors.initials: MA
authors.lastname: Arai
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Uchida
authors.affiliation: Pharmacy Discipline, Life Science School, Khulna University, Khulna 9208, Bangladesh.
authors.forename: Samir K
authors.initials: SK
authors.lastname: Sadhu
authors.affiliation: Department of Pharmaceutical Chemistry, University of Dhaka, Dhaka 1000, Bangladesh.
authors.forename: Firoj
authors.initials: F
authors.lastname: Ahmed
authors.affiliation: Temko Corporation, 4-27-4 Honcho, Nakano, Tokyo 164-0012, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Koyano
authors.affiliation: Faculty of Agriculture, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Thaworn
authors.initials: T
authors.lastname: Kowithayakorn
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan. Electronic address: mish@chiba-u.jp.
authors.forename: Masami
authors.initials: M
authors.lastname: Ishibashi
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000494:pharmacology*; D031622:Artocarpus / Q000737:chemistry*; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D024202:Electrophoretic Mobility Shift Assay; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D031331:Hyptis / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001688:Biological Products; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D004247:DNA
keywords: Artocarpus communis; Hedgehog signal; Hyptis suaveolens; Inhibitor; Natural products