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J Pharmacol Exp Ther. 2018 Jun 5. pii: jpet.118.248278. doi: 10.1124/jpet.118.248278. [Epub ahead of print]

NOVEL POLYPHENOLS THAT INHIBIT COLON CANCER CELL GROWTH AFFECTING CANCER CELL METABOLISM.

Author information

1
IMDEA Food Institute.
2
IQM-CSIC.
3
Natac Biotech.
4
IMDEA-FOOD.
5
IMDEA Food Institute; ana.ramirez@imdea.org anarosa@iqm.csic.es.

Abstract

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 anti-cancer 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 activates 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 anti-proliferative and pro-apoptotic 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.

KEYWORDS:

cancer chemotherapy; cell growth; chemotherapy; colon; drug development

PMID:
29871992
DOI:
10.1124/jpet.118.248278
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