TY - JOUR T1 - Novel Polyphenols That Inhibit Colon Cancer Cell Growth Affecting Cancer Cell Metabolism JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 377 LP - 389 DO - 10.1124/jpet.118.248278 VL - 366 IS - 2 AU - Marta Gómez de Cedrón AU - Teodoro Vargas AU - Andrés Madrona AU - Aranza Jiménez AU - María-Jesús Pérez-Pérez AU - José-Carlos Quintela AU - Guillermo Reglero AU - Ana San-Félix AU - Ana Ramírez de Molina Y1 - 2018/08/01 UR - http://jpet.aspetjournals.org/content/366/2/377.abstract N2 - New series of polyphenols with a hydrophilic galloyl-based head and a hydrophobic N-acyl tail, linked through a serinol moiety, have been synthesized and tested against colon cancer cell growth. Our structure activity relationship studies revealed that galloyl moieties are essential for growth inhibition. Moreover, the length of the N-acyl chain is crucial for the activity. Introduction of a (Z) double bond in the acyl chain increased the anticancer properties. Our findings demonstrate that 16, the most potent compound within this series, has inhibitory effects on colon cancer cell growth and metabolism (glycolysis and mitochondrial respiration) at the same time that it activates 5′AMP-activated kinase (AMPK) and induces apoptotic cell death. Based on these results, we propose that 16 might reprogram colon cancer cell metabolism through AMPK activation. This might lead to alterations on cancer cell bioenergy compromising cancer cell viability. Importantly, these antiproliferative and proapoptotic effects are selective for cancer cells. Accordingly, these results indicate that 16, with an unsaturated C18 chain, might be a useful prototype for the development of novel colon cancer cell growth inhibitors affecting cell metabolism. ER -