Life Sciences, 2014, 100(2):75-84.

Nonsteroidal anti-inflammatory drug activated gene-1 (NAG-1) modulators from natural products as anti-cancer agents

Min Hye Yang, Jinwoong Kim, Ikhlas A. Khan, et al

National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, MS 38677, USA; et al

Natural products are rich sources of gene modulators that may be useful in prevention and treatment of cancer. Recently, nonsteroidal anti-inflammatory drug (NSAID) activated gene-1 (NAG-1) has been focused as a target of action against diverse cancers like colorectal, pancreatic, prostate, and breast. A variety of natural agents have been reported to play a pivotal role in regulation of NAG-1 through multiple transcriptional mechanisms. The aim of this paper is to review the NAG-1 modulators derived from natural products including plants, marine organisms, and microorganisms. Plant extracts belonging to the families of Fabaceae (Astragalus membranaceus), Ranunculaceae (Coptis chinensis), Menispermaceae (Coscinium fenestratum), Umbelliferae (Pleurospermum kamtschaticum), Lamiaceae (Marubium vulgare), and Rosaceae (Prunus serotina) increased the protein expression of NAG-1 in human colon cancer or hepatocarcinoma cells. Phytochemicals in the class of flavonoids (apigenin, quercetin, isoliquiritigenin, and 2'-hydroxyflavanone), isoflavonoids (formononetin and genistein), catechins (epigallocatechin gallate and epicatechin gallate), stilbenoids (resveratrol and pinosylvin), phenolics (6-gingerol), phloroglucinols (rottlerin and aspidin PB), terpenoids (18 α-glycyrrhetinic acid, platycodin D, pseudolaric acid B, and xanthorrhizol), alkaloids (berberine, capsaicin, and indole-3-carbinol), lignans (isochaihulactone), anthraquinones (damnacanthal), and allyl sulfides (diallyl disulfide) elicited NAG-1 overexpression in various cancer cells. Pectenotoxin-2 from marine organisms and prodigiosin and anisomycin from microorganisms were also reported as NAG-1 modulators. Several transcription factors including EGR-1, p53, ATF-3, Sp1 and PPARγ were involved in natural products-induced NAG-1 transcriptional signaling pathway.

荷兰《生命科学》，2014年4月

来自天然产物的非甾体类抗炎药物激活的基因1(NAG-1) 调制器作为抗癌药物

杨敏慧，金进雄，艾库哈拉斯 A 科寒，等

美国密西西比大学药学院药学研究所天然产物国家研究中心等

天然产物是一种资源丰富的基因调节剂，可用于预防和治疗癌症。最近，非甾体类抗炎药 (NSAID) 激活的基因-1 (NAG-1)已经被作为对抗不同癌症如大肠癌、 胰腺癌、 前列腺癌和乳腺癌的明确靶标。多种天然药物被报道在调节NAG-1方面通过多种转录机制调节发挥着举足轻重的作用。本文的目的是综述衍生自植物、 海洋生物和微生物等天然产物的NAG-1 调节剂。植物提取物属于豆科 （黄芪），毛茛科 （黄连），防己科 （防己），伞形科 （养心草） ，唇形科 （茴香） 和蔷薇科（樱桃），可以增强 NAG-1在 人体结肠肿瘤或肝癌细胞中的蛋白表达。植物中的黄酮类化合物 （芹菜、 槲皮素、 异甘草素和 2'-羟基黄烷酮），异黄酮类化合物 （芒柄花黄素和金雀异黄素），儿茶素 （儿茶素没食子酸和表儿茶素没食子酸）、 芪类化合物 （白藜芦醇和赤松素）、 酚类物质 （6-姜酚）、间苯三酚类（粗糠柴苦素和鳞毛蕨素 PB）、 萜类化合物 （18 α-甘草次酸、 桔梗皂苷 D、 土荆皮酸 B 和黄根醇）、 生物碱 （盐酸小檗碱、 辣椒素和吲哚-3-甲醇）、 木脂素 （异柴胡内酯）、 蒽醌 （虎刺醛）和烯丙基硫化物 （二烯丙基二硫醚）等，在多种肿瘤细胞中可以诱导 NAG-1过度表达。来自海洋生物的扇贝毒素-2和来自微生物的灵菌红素与茴香毒素也被报告可以作为 NAG-1的调节剂。包括EGR-1 、p53、ATF 3、 Sp1 和 PPARγ的几种转录因子， 参与了天然产物诱导的 NAG-1 转录信号通路。