A screening of natural products using a luciferase assay targeting the Wnt signaling pathway was carried out, and the bioassay-guided fractionation of Excoecaria indica (Euphorbiaceae) collected from Bangladesh afforded three phorbol esters (1 – 3). These compounds exhibited Wnt signal-augmenting effects with 1 causing a 25-fold increase in TCF/β-catenin (TOP) transcriptional activity at 95 nM.
AngersS, MoonRT. (2009) Proximal events in Wnt signal transduction. Nature Reviews Molecular Cell Biology, 10, 468–477.
2.
MoonRT, KohnAD, De FerrariGV, KaykasA. (2004) Wnt and β-catenin signaling: diseases and therapies. Nature Reviews Genetics, 5, 689–699.
3.
TakebeN, HarrisPJ, WarrenRQ, IvySP. (2011) Targeting cancer stem cells by inhibiting Wnt, Notch, and Hedgehog pathways. Nature Reviews Clinical Oncology, 8, 97–106.
4.
EmamiKH, NguyenC, MaH, KimDH, JeongKW, EguchiM, MoonRT, TeoJL, KimHY, MoonSH, HaJR, KahnM. (2004) A small molecule inhibitor of beta-catenin/CREB-binding protein transcription [corrected]. Proceedings of the National Academy of Sciences of the United States of America, 101, 12682–12687.
ChenB, DodgeME, TangW, LuJ, MaZ, FanCW, WeiS, HaoW, KilgoreJ, WilliamsNS, RothMG, AmatrudaJF, ChenC, LumL. (2009) Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer. Nature Chemical Biology, 5, 100–107.
7.
CurtinJC, LorenziMV (2010) Drug discovery approaches to target Wnt signaling in cancer stem cells. Oncotarget, 1, 552–566.
8.
YaoH, AshiharaE, MaekawaT. (2011) Targeting the Wnt/β-catenin signaling pathway in human cancers. Expert Opinion on Therapeutic Targets, 15, 873–887.
9.
IshibashiM, AraiMA. (2009) Search for bioactive natural products targeting cancer-related signaling pathways. Journal of Synthetic Organic Chemistry, Japan, 297, 1094–1103.
10.
LiX, OhtsukiT, KoyanoT, KowithayakornT, IshibashiM. (2009) New Wnt/β-catenin signaling inhibitors isolated from Eleutherine palmifolia. Chemistry an Asian Journal, 4, 540–547.
11.
MoriN, ToumeK, AraiMA, KoyanoT, KowithayakornT, IshibashiM. (2011) 2-Methoxy-1,4-naphthoquinone isolated from Impatiens balsamina in a screening program for activity to inhibit Wnt signaling. Journal of Natural Medicines, 65, 234–236.
12.
AhmedF, SadhuSK, IshibashiM. (2010) Search for bioactive natural products from medicinal plants of Bangladesh. Journal of Natural Medicines, 64, 393–401.
13.
ChumkaewP, KaralaiC, PonglimanontC, ChantraprommaK. (2003) Antimycobacterial activity of phorbol esters from the fruits of Sapium indicum. Journal of Natural Products, 66, 540–543.
14.
ChenRH, DingWV, McCormickF. (2000) Wnt signaling to beta-catenin involves two interactive components. Glycogen synthase kinase-3beta inhibition and activation of protein kinase C. The Journal of Biological Chemistry, 275, 17894–17899.
15.
BrooksG, EvansAT, AitkenA, EvansFJ. (1989) Tumor-promoting and hyperplastic effects of phorbol and daphnane esters in CD-1 mouse skin and a synergistic effect of calcium ionophore with the non-promoting activator of protein kinase C, sapintoxin A. Carcinogenesis, 10, 283–288.
