TY - JOUR
T1 - Hedgehog inhibitors from Artocarpus communis and Hyptis suaveolens
AU - Arai, Midori A.
AU - Uchida, Kyoko
AU - Sadhu, Samir K.
AU - Ahmed, Firoj
AU - Koyano, Takashi
AU - Kowithayakorn, Thaworn
AU - Ishibashi, Masami
N1 - Funding Information:
This study was supported by a Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS), a Grant-in-Aid for Scientific Research on Innovative Areas ‘Chemical Biology of Natural Products’ from The Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT), Terumo Life Science Foundation and the Tokyo Biochemical Research Foundation (TBRF).
Publisher Copyright:
© 2015 Elsevier Ltd. All rights reserved. All rights reserved.
PY - 2015/7/23
Y1 - 2015/7/23
N2 - 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.
AB - 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.
KW - Artocarpus communis
KW - Hedgehog signal
KW - Hyptis suaveolens
KW - Inhibitor
KW - Natural products
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U2 - 10.1016/j.bmc.2015.06.058
DO - 10.1016/j.bmc.2015.06.058
M3 - Article
C2 - 26178912
AN - SCOPUS:84937514259
VL - 23
SP - 4150
EP - 4154
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
SN - 0968-0896
IS - 15
ER -