Abstract 4867: The metabolomic signature of Rhodiola rosea L. extracts- (SHR-5) treated mouse bladder cancer in the UPII-mutant Ha-ras transgenic model

Rhodiola rosea has been used for centuries in the traditional medicine for reducing depression, enhancing work performance, and preventing high altitude sickness. We have recently shown that Rhodiola rosea L. extract, SHR-5, markedly inhibited the growth of bladder cancer and the survival of mice in the UP-II-mutant Ha-ras transgenic model via inhibition of the mTOR pathway. The purpose of this study was to further investigate the effects of SHR-5 on bladder tumor metabolism. The global metabolic profiles were compared for bladder tumors from mice that were fed with normal drinking water (n=7), 1.25 (n=7) or 6.25 (n=7) mg/ml SHR-5 in water for about five months. The analysis was conducted at Metabolon Inc. with a combination of high-throughput LC- and GC-based MS method. From a metabolomics library consisting of more than 2,000 standards, a total of 341 named metabolites were detected. Phenolic metabolites, such as phenylpropionylglycine, hydroxycinnamate and catechol sulfate, were increased, while prostaglandin metabolites, such as prostaglandins A2, D2 and E2, were decreased in tumors treated with SHR-5. This observation suggested the potential anti-inflammation effect of SHR-5 in bladder tumors. Neurotransmitters GABA, taurine, NAA and 2-oxoindole-3-acetate was more abundant; whereas kynurenine, histamine and aminoadipate were less abundant with SHR-5 treatment. This result is consistent with mood-improving effects of SHR-5. In addition, SHR-5 treatment resulted in increased levels of glucose and glycogen metabolites (e.g. maltotriose, maltose), as well as two glycolysis intermediates (3-phosphoglycerate and 2-phosphoglycerate) and the citric acid cycle (TCA) intermediates (fumarate and malate) compared to control treatment. These patterns suggest that SHR-5 may increase mobilization of glycogen for energy production in glycolysis and TCA cycle. These effects of SHR-5 may be mediated by differential effects on the mTOR pathway. Taken together, we show that global metabolomic profiling provides a unique and efficient tool for studying mechanisms of complex herb extracts’ action. Citation Format: Zhongbo Liu, Christopher A. Blair, Xiaolin Zi. The metabolomic signature of Rhodiola rosea L. extracts- (SHR-5) treated mouse bladder cancer in the UPII-mutant Ha-ras transgenic model. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(