TY - JOUR
T1 - Isolation and evaluation of hedgehog inhibitors from christmas grass (themeda arguens)
AU - Yoneyama, Tatsuro
AU - Arai, Midori A.
AU - Koyano, Takashi
AU - Kowithayakorn, Thaworn
AU - Ishibashi, Masami
N1 - Publisher Copyright:
© 2017 The Japan Institute of Heterocyclic Chemistry Received.
PY - 2017
Y1 - 2017
N2 - The hedgehog (Hh) signaling pathway is an important regulator of embryonic development, tissue patterning, cellular proliferation and differentiation. However, aberrant activation of the pathway is associated with tumorigenesis. In this study, the Hh signal inhibitory activity of plant extracts was measured with a cell-based assay system that targets GLI1-mediated transcription. Activity guided analysis of MeOH extracts of christmas grass (Themeda arguens) led to the isolation of four inhibitory compounds: Aciculatin (1), 7-de-O-methylaciculatin (2), 8-C-D-boivinopyranosylapigenin (3) and aciculatinone (4). Compound 1 strongly inhibited Hh/GLI1-mediated transcriptional activity with an IC50 value of 1.8 ΓM, and disrupted the formation of the GLI1-DNA complex by EMSA. 1 and 3 were cytotoxic for human prostate (DU-145) and breast (MCF-7) cancer cells. These compounds may serve as new tools for the molecular dissection of Hh pathway activation.
AB - The hedgehog (Hh) signaling pathway is an important regulator of embryonic development, tissue patterning, cellular proliferation and differentiation. However, aberrant activation of the pathway is associated with tumorigenesis. In this study, the Hh signal inhibitory activity of plant extracts was measured with a cell-based assay system that targets GLI1-mediated transcription. Activity guided analysis of MeOH extracts of christmas grass (Themeda arguens) led to the isolation of four inhibitory compounds: Aciculatin (1), 7-de-O-methylaciculatin (2), 8-C-D-boivinopyranosylapigenin (3) and aciculatinone (4). Compound 1 strongly inhibited Hh/GLI1-mediated transcriptional activity with an IC50 value of 1.8 ΓM, and disrupted the formation of the GLI1-DNA complex by EMSA. 1 and 3 were cytotoxic for human prostate (DU-145) and breast (MCF-7) cancer cells. These compounds may serve as new tools for the molecular dissection of Hh pathway activation.
UR - http://www.scopus.com/inward/record.url?scp=85025621888&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85025621888&partnerID=8YFLogxK
U2 - 10.3987/COM-16-S(S)4
DO - 10.3987/COM-16-S(S)4
M3 - Article
AN - SCOPUS:85025621888
SN - 0385-5414
VL - 95
SP - 210
EP - 222
JO - Heterocycles
JF - Heterocycles
IS - 1
ER -
