title: 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 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.
authors.affiliation: Department of Physiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Nittaya
authors.initials: N
authors.lastname: Boonmuen
authors.affiliation: Department of Physiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Natthakan
authors.initials: N
authors.lastname: Thongon
authors.affiliation: Department of Physiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Arthit
authors.initials: A
authors.lastname: Chairoungdua
authors.affiliation: Department of Physiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Kanoknetr
authors.initials: K
authors.lastname: Suksen
authors.affiliation: Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Lampang Rajabhat University, Lampang 52100, Thailand.
authors.forename: Wilart
authors.initials: W
authors.lastname: Pompimon
authors.affiliation: Department of Chemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Patoomratana
authors.initials: P
authors.lastname: Tuchinda
authors.affiliation: Department of Chemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand; Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Vichai
authors.initials: V
authors.lastname: Reutrakul
authors.affiliation: Department of Physiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand; Chakri Naruebodindra Medical Institute, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand. Electronic address: pawinee.pia@mahidol.ac.th.
authors.forename: Pawinee
authors.initials: P
authors.lastname: Piyachaturawat
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D054335:Goniothalamus / Q000737:chemistry; D006801:Humans; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology; D011753:Pyrones / Q000494:pharmacology*; D051820:TCF Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D060449:Wnt Signaling Pathway / Q000187:drug effects*
chemical_list: C000616292:5-acetyl goniothalamin; D000970:Antineoplastic Agents; D007783:Lactones; D011753:Pyrones; D051820:TCF Transcription Factors; C103280:goniothalamin
keywords: 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) (PubChem CID:64965); 5-Acetyl goniothalamin; 5-bromo-2′-deoxyuridine (BrdU) (PubChem CID: 6035); Anticancer; Antiproliferation; Breast cancer; Doxorubicin (PubChem CID: 31703); Ellipticine (PubChem CID:3213); Propidium iodide (PI) (PubChem CID: 104981); Styryl lactone; Wnt signaling