Metabolic profiling-based data-mining for an effective chemical combination to induce apoptosis of cancer cells.
Metabolic profiling-based data-mining for an effective chemical combination to induce apoptosis of cancer cells.
复制标题
DOI：
10.1038/srep09474
复制
发表时间：
2015-03-31
影响因子：
4.6
通讯作者：
Tachibana H
中科院分区：
文献类型：
--
作者：
Kumazoe M;Fujimura Y;Hidaka S;Kim Y;Murayama K;Takai M;Huang Y;Yamashita S;Murata M;Miura D;Wariishi H;Maeda-Yamamoto M;Tachibana H
绿茶提取物（GTE）在不影响正常细胞的情况下诱导癌细胞凋亡。一些临床试验报道GTE耐受性良好，具有潜在的抗癌功效。表没食子儿茶素-3- o -没食子酸酯（EGCG）是GTE抗癌作用的主要化合物；然而，EGCG单独的作用是有限的。为了鉴定能够增强EGCG生物活性的GTE化合物，我们使用液相色谱-质谱（LC-MS）对43个绿茶品种进行了代谢谱分析。在体外和小鼠肿瘤模型中，我们发现多酚戊二醇通过增强EGCG诱导的67-kDa层粘连蛋白受体(67LR)/蛋白激酶B/内皮型一氧化氮合酶/蛋白激酶C δ /酸性鞘磷脂酶信号通路的激活，显著增强了EGCG诱导的细胞凋亡。我们的研究结果表明，代谢谱是一种有效的化学挖掘方法，用于鉴定具有治疗多发性骨髓瘤潜力的植物性药物。基于代谢谱的数据挖掘可能是筛选其他生物活性化合物和确定有效化学组合的有效策略。
Green tea extract (GTE) induces apoptosis of cancer cells without adversely affecting normal cells. Several clinical trials reported that GTE was well tolerated and had potential anti-cancer efficacy. Epigallocatechin-3-O-gallate (EGCG) is the primary compound responsible for the anti-cancer effect of GTE; however, the effect of EGCG alone is limited. To identify GTE compounds capable of potentiating EGCG bioactivity, we performed metabolic profiling of 43 green tea cultivar panels by liquid chromatography–mass spectrometry (LC–MS). Here, we revealed the polyphenol eriodictyol significantly potentiated apoptosis induction by EGCG in vitro and in a mouse tumour model by amplifying EGCG-induced activation of the 67-kDa laminin receptor (67LR)/protein kinase B/endothelial nitric oxide synthase/protein kinase C delta/acid sphingomyelinase signalling pathway. Our results show that metabolic profiling is an effective chemical-mining approach for identifying botanical drugs with therapeutic potential against multiple myeloma. Metabolic profiling-based data mining could be an efficient strategy for screening additional bioactive compounds and identifying effective chemical combinations.
登录
查看更多内容
影响因子：
3.8
作者：
Goodacre, R;York, EV;Scott, IM
通讯作者：
Scott, IM
影响因子：
3.7
作者：
Lee, Ju Hye;Kishikawa, Mutsumi;Tachibana, Hirofumi
通讯作者：
Tachibana, Hirofumi
影响因子：
7.4
作者：
Cuadros-Inostroza, Alvaro;Giavalisco, Patrick;Pena-Cortes, Hugo
通讯作者：
Pena-Cortes, Hugo
影响因子：
3.9
作者：
Punyasiri, PAN;Abeysinghe, ISB;Fischer, TC
通讯作者：
Fischer, TC
影响因子：
3.6
作者：
Dunn, W. B.;Overy, S.;Quick, W. P.
通讯作者：
Quick, W. P.