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Title

Novel polyphenols that inhibit colon cancer cell growth affecting cancer cell metabolisms

AuthorsGómez de Cedrón, Marta; Vargas, Teodoro; Madrona, A.; Jiménez, A.; Peréz-Pérez, María-Jesús ; Quintela, J. C.; Reglero, Guillermo ; San-Félix, Ana ; Ramírez de Molina, Ana
Issue Date2018
PublisherAmerican Society for Pharmacology and Experimental Therapeutics
CitationJournal of Pharmacology and Experimental Therapeutics 366: 377-389 (2018)
AbstractNew 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 59AMP-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.
Publisher version (URL)http://dx.doi.org/10.1124/jpet.118.248278
URIhttp://hdl.handle.net/10261/178440
Identifiersdoi: 10.1124/jpet.118.248278
issn: 0022-3565
e-issn: 1521-0103
Appears in Collections:(IQM) Artículos
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