Rosemary polyphenols induce unfolded protein response and changes in cholesterol metabolism in colon cancer cells

Several studies have demonstrated that rosemary polyphenols exert changes in the lipid metabolism in adipose and hepatic cells. In this work, the effects of a polyphenol-enriched supercritical rosemary extract (SC-RE) and carnosic acid (CA) on the transcriptome and cholesterol metabolism in HT-29 colon cancer cells were examined using a Foodomics approach. Targeted metabolomics analysis indicated that the SC-RE treatment induced cholesterol accumulation after 24 h. Transcriptomic analysis suggested that most of the changes induced by the SC-RE and CA were orchestrated by unfolded protein response (UPR) and triggered by endoplasmic reticulum stress. Results suggested up-regulation of VLDLR gene as the principal contributor to the observed cholesterol accumulation in SC-RE-treated cells. In addition, the SC-RE attenuated the activity of E2F transcription factor, down-regulating several genes involved in G1-S transition of the cell cycle.This work was supported by an AGL2011-29857-C03-01 project (Ministerio de Educacion y Ciencia, Spain) and S2013/ABI-2728 (Comunidad de Madrid). A.V. thanks the Ministerio de Economía y Competitividad for his FPI pre-doctoral fellowship (BES-2012-057014).Peer Reviewe