Boonmuen Nittaya, Thongon Natthakan, Chairoungdua Arthit, Suksen Kanoknetr, Pompimon Wilart, Tuchinda Patoomratana, Reutrakul Vichai, Piyachaturawat Pawinee
Department of Physiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Lampang Rajabhat University, Lampang 52100, Thailand.
Eur J Pharmacol. 2016 Nov 15;791:455-464. doi: 10.1016/j.ejphar.2016.09.024. Epub 2016 Sep 16.
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 G 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.
苯乙烯基内酯是一种从哥纳香属植物中提取的化合物，具有良好的抗增殖和抗癌特性。然而，其确切的作用机制和靶点仍不清楚。在本研究中，我们研究了来自大叶哥纳香的5-乙酰哥纳甜素（5GTN）对Wnt/β-连环蛋白信号通路的影响，该信号通路是控制乳腺癌细胞（MCF-7和MDA-MB-231）增殖的关键调节因子。5GTN是哥纳甜素（GTN）的天然衍生物，以剂量和时间相关的方式介导对MCF-7和MDA-MB-231细胞的毒性，且比GTN更有效。在荧光素酶报告基因检测中，5GTN强烈抑制细胞增殖并显著抑制β-连环蛋白诱导的转录活性。与此观点一致，用5GTN处理后，MCF-7和MDA-MB-231细胞中包括c-Myc、细胞周期蛋白D1和Axin2在内的Wnt/β-连环蛋白信号靶基因的表达受到抑制。这与MCF-7细胞在G期的细胞周期停滞和细胞凋亡相伴。此外，5GTN增强了糖原合酶激酶（GSK-3β）的活性，因此降低了MCF-7和MDA-MB-231细胞中活性形式的β-连环蛋白的表达。综上所述，5GTN通过抑制Wnt/β-连环蛋白信号通路对乳腺癌细胞表现出有前景的抗癌作用。该通路可能是5GTN治疗乳腺癌的潜在化疗靶点。
