Abstract 163: Metabolomic profiling reveals a protective modulation on fatty acid metabolism in colorectal cancer patients following consumption of freeze-dried black raspberries.

Metabolic reprogramming which refers to altered nutrient uptake and use is thought to be essential for rapid cancer cell proliferation. Accelerated phospholipid biosynthesis is another metabolic signature of cancer because proliferating cells have a significant need for membrane production. Fatty acids that compose the hydrophobic tails of membrane phospholipids can regulate gene transcription through enzyme-mediated pathways, e.g., cyclooxygenase, lipoxygenase, and changing lipid raft composition that affect receptor-mediated signalings. We previously showed that dietary intervention with freeze-dried black raspberries (BRBs) decreased cell proliferation in colorectal tumors and IL-8, a pro-inflammatory cytokine, in plasma in colorectal cancer patients. The goal of the current study was to determine if BRBs affect fatty acid metabolism which may contribute to their anti-proliferative and anti-inflammatory activities. Plasma samples were collected from 28 colorectal cancer patients before and after oral consumption of BRB powder (60g/day) for 1-to-9 wks for metabolomic profiling analysis. 421 biochemicals were analyzed using UHPLC/Gas chromatography and mass spectrometry. When data from all 28 patients were combined, the top 30 ranking biochemicals suggest that berry intervention led to alterations mostly in lipids, following by carbohydrates, amino acids, and cofactors and vitamins. Both monounsaturated fatty acids (MUFAs), e.g., eicosenoate (20:1n9 or 11), and polyunsaturated fatty acids (PUFAs), e.g., linoleate (18:2n6), arachidonate (20:4n6), were lower in the post plasma samples. PUFAs can be synthesized from linoleate and they also can be released by phospholipase A from phospholipid membrane. Therefore, berry intervention might alter activities of phospholipase A, elongases, and desaturases which in turn reduce levels of PUFAs. Alternatively, berry intervention increased secondary bile acids, e.g., glycodeoxycholate, produced by the action of enzymes existing in the microbial flora of the colonic environment, suggesting dietary BRBs could alter colonic microflora. Berry intervention associated alternations in bile acid metabolism could affect fat absorption and subsequently impact fatty acid metabolism. In conclusion, our results suggest that dietary berry consumption protectively modulates enzymes associated with fatty acid metabolism in the host as well as in gut microflora leading to decreased proliferation and inflammation in colorectal cancer patients. Supported by R01 CA148818 to L-S Wang Citation Format: Li-Shu Wang, Matthew Young, Chieh-Ti Kuo, Mark Arnold, Edward Martin, Christine Sardo, Gary Stoner. Metabolomic profiling reveals a protective modulation on fatty acid metabolism in colorectal cancer patients following consumption of freeze-dried black raspberries. [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(8 Suppl):Abstract nr 163. doi:10.1158/1538-7445.AM2013-163