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Inhibition of β‐Catenin Signaling by 3‐Acetylaltholactone in Cancer Cells
Author(s) -
Boonmuen Nittaya,
Chairoungdua Arthit,
Tuchinda Patoomratana,
Piyachaturawat Pawinee
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1227.6
Subject(s) - wnt signaling pathway , cancer research , signal transduction , catenin , microbiology and biotechnology , transcription factor , cancer cell , biology , lrp6 , cell growth , chemistry , cancer , gene , biochemistry , genetics
Wnt/β‐catenin signaling pathway is a complex protein interaction network which plays important functions in cell proliferation, survival and differentiation during animal development and in disease conditions. In Wnt pathway, binding of Wnt ligand to its receptors at the plasma membrane results in inactivation of the β‐catenin destruction complex and promotes the accumulation of β‐catenin translocation from cytoplasm into the nucleus to initiate the transcription of Wnt‐responsive gene expression by binding with TCF/LEF transcription factor. The aberrant regulation of Wnt/β‐catenin signaling has been found to associate with many human diseases including cancers. Therefore, it has been highlighted as a promising target for anti‐cancer drugs. In the present study, we reported the inhibitory effect of 3‐acetylaltholactone, a plant‐derived compound from Goniothalamus sp on the Wnt/β‐catenin signaling pathway in cancer cells. The compound inhibited growth of breast cancers (MCF‐7, and MDA‐MB‐231) and endometrial adenocarcinoma (Ishikawa cell lines). It effectively decreased the expression of β‐catenin protein in breast cancer cells and inhibited TCF/LEF mediated transcriptional activity in HEK293 cells. In addition, 3‐acetylaltholactone also decreased the mRNA expressions of Wnt signaling target genes in MCF‐7 cells. Moreover, it inhibited cell migration by using wound healing assay in MDA‐MB‐231 cells, a highly metastatic human breast carcinoma cell line. In conclusion, these results suggest that 3‐acetylaltholactone mediates anticancer effect on breast cancer cells through inhibition of the Wnt/β‐catenin signaling pathway. Support or Funding Information Supported by Mahidol University, TRF through RGJ‐ Ph.D. Program (PHD/0170/2552 to PP and NB), and IRN58W0004.