title: Hedgehog/GLI-mediated transcriptional activity inhibitors from Crinum asiaticum.
abstract: The inhibition of the hedgehog (Hh) signaling pathway has emerged as an attractive anti-cancer strategy. As part of our continuing search for natural inhibitors of the Hh/GLI1 signaling pathway, we isolated three alkaloids (1-3) from Crinum asiaticum. Compounds 1 and 3 showed potent Hh/GLI1-mediated transcriptional inhibitory activity and exhibited cytotoxicity against human pancreatic (PANC1) and prostate (DU145) cancer cells. Our data revealed that compounds 1 and 3 clearly inhibited the Hh signaling pathway by down-regulating the expression of GLI-related proteins (PTCH and BCL2) in DU145 cells.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8675, Japan, midori_arai@chiba-u.jp.
authors.forename: Midori A
authors.initials: MA
authors.lastname: Arai
authors.forename: Ryuta
authors.initials: R
authors.lastname: Akamine
authors.forename: Samir K
authors.initials: SK
authors.lastname: Sadhu
authors.forename: Firoj
authors.initials: F
authors.lastname: Ahmed
authors.forename: Masami
authors.initials: M
authors.lastname: Ishibashi
mesh_terms: D031407:Crinum / Q000737:chemistry*; D015536:Down-Regulation; D053823:Hedgehog Proteins / Q000737:chemistry*; D006801:Humans; D010946:Plants, Medicinal / Q000737:chemistry*; D015398:Signal Transduction; D014157:Transcription Factors / Q000737:chemistry*; D015533:Transcriptional Activation; D000071676:Zinc Finger Protein GLI1
chemical_list: C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1