PT  - JOURNAL ARTICLE
AU  - Gómez de Cedrón, Marta
AU  - Vargas, Teodoro
AU  - Madrona, Andrés
AU  - Jiménez, Aranza
AU  - Pérez-Pérez, María-Jesús
AU  - Quintela, José-Carlos
AU  - Reglero, Guillermo
AU  - San-Félix, Ana
AU  - Ramírez de Molina, Ana
TI  - Novel Polyphenols That Inhibit Colon Cancer Cell Growth Affecting Cancer Cell Metabolism
AID  - 10.1124/jpet.118.248278
DP  - 2018 Aug 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 377--389
VI  - 366
IP  - 2
4099  - http://jpet.aspetjournals.org/content/366/2/377.short
4100  - http://jpet.aspetjournals.org/content/366/2/377.full
SO  - J Pharmacol Exp Ther2018 Aug 01; 366
AB  - 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.