Weng Jing-Ru, Bai Li-Yuan, Lin Wei-Yu
Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, 80424, Taiwan.
Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung, 40447, Taiwan.
Phytother Res. 2017 Nov;31(11):1722-1730. doi: 10.1002/ptr.5900. Epub 2017 Aug 30.
Peroxisome proliferator-activated receptor γ (PPARγ), one of the transcription factors that regulate lipid metabolism and energy use in tumor cells, is a viable target for cancer therapy. In our search for potential PPARγ activator, extracts from five Formosan plants were tested. Among them, Momordica charantia L. showed the highest ability to activate PPARγ, which led us to identify its potential constituents. Among the seven compounds isolated from M. charantia, a triterpenoid, 5β,19-epoxy-19-methoxycucurbita-6,23-dien-3β,25-diol (compound 1), was identified as a PPARγ activator with an IC of 10 μM in breast cancer MCF-7 cells. Flow cytometric analysis indicated that compound 1 induced G1 cell cycle arrest which might be attributable to the modulation of phosphorylation and expression of numerous key signaling effectors, including cyclin D1, CDK6, and p53. Notably, compound 1 downregulated the expression of histone deacetylase 1, leading to increased histone H3 acetylation. Taken together, these findings suggest that compound 1 may have therapeutic applications in cancer treatment through PPARγ activation. Copyright © 2017 John Wiley & Sons, Ltd.
过氧化物酶体增殖物激活受体γ（PPARγ）是调节肿瘤细胞脂质代谢和能量利用的转录因子之一，是癌症治疗的一个可行靶点。在我们寻找潜在的PPARγ激活剂的过程中，对五种台湾植物的提取物进行了测试。其中，苦瓜表现出最高的激活PPARγ的能力，这促使我们确定其潜在成分。在从苦瓜中分离出的七种化合物中，一种三萜类化合物，5β,19-环氧-19-甲氧基葫芦巴-6,23-二烯-3β,25-二醇（化合物1），被鉴定为在乳腺癌MCF-7细胞中IC为10μM的PPARγ激活剂。流式细胞术分析表明，化合物1诱导G1期细胞周期停滞，这可能归因于对包括细胞周期蛋白D1、细胞周期蛋白依赖性激酶6和p53在内的众多关键信号效应器的磷酸化和表达的调节。值得注意的是，化合物1下调组蛋白去乙酰化酶1的表达，导致组蛋白H3乙酰化增加。综上所述，这些发现表明化合物1可能通过激活PPARγ在癌症治疗中具有治疗应用。版权所有©2017约翰威立父子有限公司。
