Molecular Oncology and Nutritional Genomics of Cancer, IMDEA-Food Institute, CEI UAM+CSIC, Madrid, Spain (M.G.d.C., T.V., G.R., A.R.d.M.); Instituto de Química Médica (IQM, CSIC), Juan de la Cierva 3, Madrid, Spain (A.M., A.J., M.-J.P.-P., A.S.-F.); and Natac Biotech S.L., Parque Científico de Madrid, Campus de Cantoblanco, Madrid, Spain (J.-C.Q.).
Molecular Oncology and Nutritional Genomics of Cancer, IMDEA-Food Institute, CEI UAM+CSIC, Madrid, Spain (M.G.d.C., T.V., G.R., A.R.d.M.); Instituto de Química Médica (IQM, CSIC), Juan de la Cierva 3, Madrid, Spain (A.M., A.J., M.-J.P.-P., A.S.-F.); and Natac Biotech S.L., Parque Científico de Madrid, Campus de Cantoblanco, Madrid, Spain (J.-C.Q.)
J Pharmacol Exp Ther. 2018 Aug;366(2):377-389. doi: 10.1124/jpet.118.248278. Epub 2018 Jun 5.
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.
已合成了一系列具有亲水没食子酰基头部和疏水酰基尾部的新型多酚，通过丝氨醇部分连接，并用其测试对结肠癌细胞生长的抑制作用。我们的结构活性关系研究表明，没食子酰基是抑制生长所必需的。此外，酰基链的长度对活性至关重要。在酰链中引入（）双键会增加抗癌特性。我们的研究结果表明，该系列中最有效的化合物 ，同时对结肠癌细胞生长和代谢（糖酵解和线粒体呼吸）具有抑制作用，同时激活 5'AMP 激活的蛋白激酶（AMPK）并诱导细胞凋亡。基于这些结果，我们提出 可能通过 AMPK 激活重新编程结肠癌细胞代谢。这可能导致癌症细胞生物能量的改变，从而损害癌症细胞的活力。重要的是，这些抗增殖和促凋亡作用对癌细胞是特异的。因此，这些结果表明，具有不饱和 C18 链的 ，可能是开发影响细胞代谢的新型结肠癌细胞生长抑制剂的有用原型。
