Lodi Alessia, Saha Achinto, Lu Xiyuan, Wang Bo, Sentandreu Enrique, Collins Meghan, Kolonin Mikhail G, DiGiovanni John, Tiziani Stefano
Department of Nutritional Sciences, The University of Texas at Austin, Austin, TX, USA.
Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX, USA.
NPJ Precis Oncol. 2017;1. doi: 10.1038/s41698-017-0024-z. Epub 2017 Jun 5.
High-throughput screening of a natural compound library was performed to identify the most efficacious combinatorial treatment on prostate cancer. Ursolic acid, curcumin and resveratrol were selected for further analyses and administered in vivo via the diet, either alone or in combination, in a mouse allograft model of prostate cancer. All possible combinations of these natural compounds produced synergistic effects on tumor size and weight, as predicted in the screens. A subsequent untargeted metabolomics and metabolic flux analysis using isotopically labeled glutamine indicated that the compound combinations modulated glutamine metabolism. In addition, ASCT2 levels and STAT3, mTORC1 and AMPK activity were modulated to a greater extent by the combinations compared to the individual compounds. Overall, this approach can be useful for identifying synergistic combinations of natural compounds for chemopreventive and therapeutic interventions.
为了确定对前列腺癌最有效的联合治疗方法，对一个天然化合物文库进行了高通量筛选。选择了熊果酸、姜黄素和白藜芦醇进行进一步分析，并在前列腺癌小鼠异种移植模型中通过饮食单独或联合给药。如筛选中所预测的，这些天然化合物的所有可能组合对肿瘤大小和重量产生了协同作用。随后使用同位素标记的谷氨酰胺进行的非靶向代谢组学和代谢通量分析表明，化合物组合调节了谷氨酰胺代谢。此外，与单个化合物相比，组合对ASCT2水平以及STAT3、mTORC1和AMPK活性的调节作用更大。总体而言，这种方法对于识别用于化学预防和治疗干预的天然化合物协同组合可能是有用的。
