5-Acetyl goniothalamin suppresses proliferation of breast cancer cells via Wnt/β-catenin signaling.

Abstract

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 G1 phase 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.

• Authors: Nittaya Boonmuen, Natthakan Thongon, Arthit Chairoungdua, Kanoknetr Suksen, Wilart Pompimon, Patoomratana Tuchinda, Vichai Reutrakul, Pawinee Piyachaturawat
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 791 Pg. 455-464 (Nov 15 2016) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 27640746 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical References

• 5-acetyl goniothalamin
• Antineoplastic Agents
• Lactones
• Pyrones
• TCF Transcription Factors
• goniothalamin

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Breast Neoplasms (pathology)
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Goniothalamus (chemistry)
• Humans
• Lactones (chemistry, pharmacology)
• Pyrones (pharmacology)
• TCF Transcription Factors (metabolism)
• Transcription, Genetic (drug effects)
• Wnt Signaling Pathway (drug effects)