TY - JOUR
T1 - 5-Acetyl goniothalamin suppresses proliferation of breast cancer cells via Wnt/β-catenin signaling
AU - Boonmuen, Nittaya
AU - Thongon, Natthakan
AU - Chairoungdua, Arthit
AU - Suksen, Kanoknetr
AU - Pompimon, Wilart
AU - Tuchinda, Patoomratana
AU - Reutrakul, Vichai
AU - Piyachaturawat, Pawinee
N1 - Funding Information:
This research project is supported by the Thailand Research Fund (TRF)-Mahidol University through the Royal Golden Jubilee Ph.D. Program (PHD/0170/2552 to PP and NB), the research grants from Mahidol University, and the TRF through the International Research Network (IRN-58W0004), and the plant compounds from the Center of Excellence for Innovation in Chemistry (PERCH-CIC). We are grateful to Prof. Chumpol Pholpramool for his critical reading of the manuscript.
Publisher Copyright:
© 2016 Elsevier B.V.
PY - 2016
Y1 - 2016
N2 - Styryl lactones are plant-derived compounds from genus Goniothalamus with promising anti-proliferation and anticancer properties. However, the exact mechanism and the target for their activities remained unclear. In the present study, we investigated the effect of 5-acetyl goniothalamin (5GTN) from Goniothalamus marcanii on Wnt/β-catenin signaling pathway which is a key regulator in controlling cell proliferation in breast cancer cells (MCF-7 and MDA-MB-231). 5GTN, a naturally occurring derivative of goniothalamin (GTN) mediated the toxicity to MCF-7 and MDA-MB-231 cells in a dose- and time- related manner, and was more potent than that of GTN. 5GTN strongly inhibited cell proliferation and markedly suppressed transcriptional activity induced by β-catenin in luciferase reporter gene assay. In consistent with this view, the expression of Wnt/β-catenin signaling target genes including c-Myc, cyclin D1 and Axin2 in MCF-7 and MDA-MB-231 cells were suppressed after treatment with 5GTN. It was concomitant with cell cycle arrest at G1phase and cell apoptosis in MCF-7 cells. In addition, 5GTN enhanced glycogen synthase kinase (GSK-3β) activity and therefore reduced the expression of active form of β-catenin protein in MCF-7 and MDA-MB-231 cells. Taken together, 5GTN exhibited a promising anticancer effect against breast cancer cells through an inhibition of Wnt/β-catenin signaling. This pathway may be served as a potential chemotherapeutic target for breast cancer by 5GTN.
AB - Styryl lactones are plant-derived compounds from genus Goniothalamus with promising anti-proliferation and anticancer properties. However, the exact mechanism and the target for their activities remained unclear. In the present study, we investigated the effect of 5-acetyl goniothalamin (5GTN) from Goniothalamus marcanii on Wnt/β-catenin signaling pathway which is a key regulator in controlling cell proliferation in breast cancer cells (MCF-7 and MDA-MB-231). 5GTN, a naturally occurring derivative of goniothalamin (GTN) mediated the toxicity to MCF-7 and MDA-MB-231 cells in a dose- and time- related manner, and was more potent than that of GTN. 5GTN strongly inhibited cell proliferation and markedly suppressed transcriptional activity induced by β-catenin in luciferase reporter gene assay. In consistent with this view, the expression of Wnt/β-catenin signaling target genes including c-Myc, cyclin D1 and Axin2 in MCF-7 and MDA-MB-231 cells were suppressed after treatment with 5GTN. It was concomitant with cell cycle arrest at G1phase and cell apoptosis in MCF-7 cells. In addition, 5GTN enhanced glycogen synthase kinase (GSK-3β) activity and therefore reduced the expression of active form of β-catenin protein in MCF-7 and MDA-MB-231 cells. Taken together, 5GTN exhibited a promising anticancer effect against breast cancer cells through an inhibition of Wnt/β-catenin signaling. This pathway may be served as a potential chemotherapeutic target for breast cancer by 5GTN.
KW - 5-Acetyl goniothalamin
KW - Anticancer
KW - Antiproliferation
KW - Breast cancer
KW - Styryl lactone
KW - Wnt signaling
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U2 - 10.1016/j.ejphar.2016.09.024
DO - 10.1016/j.ejphar.2016.09.024
M3 - Article
C2 - 27640746
AN - SCOPUS:84988486919
SN - 0014-2999
VL - 791
SP - 455
EP - 464
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
ER -