Novel Polyphenols That Inhibit Colon Cancer Cell Growth Affecting Cancer Cell Metabolism

Abstract

New series of polyphenols with a hydrophilic galloyl-based head and a hydrophobic -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-acyl chain is crucial for the activity. Introduction of a () double bond in the acyl chain increased the anticancer properties. Our findings demonstrate that , 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 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 , with an unsaturated C18 chain, might be a useful prototype for the development of novel colon cancer cell growth inhibitors affecting cell metabolism.

Cancer Glycolytic Dependence as a New Target of Olive Leaf Extract

“…In line with our results, Sharma and colleagues showed that morin and/or esculetin impaired glycolysis and glutaminolysis preventing colon carcinogenesis [31]. Moreover, Gomez de Cedron and colleagues identified a new series of polyphenols characterized by a galloyl based "head" and a hydrophobic N-acyl "tail", able to inhibit glycolysis and mitochondrial respiration in colon cancer cells [32].…”

“…The K M value of GLUT1 for glucose is near 1 mM, a significantly less amount compared to the normal glucose level found in serum, allowing a relentless glucose transport into the cells. Of interest, GLUT1 represents the predominant glucose transporter isoform of fetus tissues, which exhibit a higher growth rate than adult ones, at comparable levels to those observed in tumor cells, requiring an increased supply of energy-producing substrates [32]. After birth, GLUT1 expression levels decrease and, even though the reasons behind its decline are not yet clear, it could occur a possible switch form a carbohydrate to a fat source of fuel that may induce this change in some organs [33].…”

A Novel Class of Cationic and Non-Peptidic Small Molecules as Hits for the Development of Antimicrobial Agents

“…According to the general procedure serinol 4 (150 mg, 1.64 mmol) was treated with 9-octadecenoyl chloride (oleoyl chloride) (541.6 mg, 0.6 mL) and TEA (0.4 mL) to give 375 mg (64%) of 8 as an amorphous white solid. Spectroscopic data of this compound are consistent with those found in the literature [ 33 ].…”

Biologically active metabolite(s) from haemolymph of red-headed centipede Scolopendra subspinipes possess broad spectrum antibacterial activity

“…Similar structure: anti-inflammatory and pain-relieving effects (Britti et al 2017), useful in the treatment of inflammatory and neurodegenerative disorders (Barbierato et al 2018), anticancer activity against colon cancer cell growth (de Cedrón et al 2018), beneficial in the treatment of HIV-1 associated neurocognitive disorders (HAND) (Hermes et al 2018), anticancer activity against endometrial cancer (Fonseca et al 2018), useful in the treatment of intestinal barrier dysfunction (Antón et al 2018)…”