Fact, based on its capacity to modulate O2 availability and to enhance mitochondrial respiratory metabolism, we wondered if CF could influence cancer cell metabolism generating cells susceptible to apoptosis. Solutions: Three leukemic cell lines, Jurkat, U937, and K562, have been treated with CF 5 l/ml up to 72 hours. Cell viability, apoptosis (i.e. caspase-3 activity and DNA fragmentation), hypoxia inducible factor 1 alpha (HIF-1) concentration, glucose transporter 1 (GLUT-1) expression, lactate dehydrogenase (LDH) activity and lactate release within the culture medium had been detected and compared with untreated cells. Results: CF significantly inhibited leukemic cell viability by promoting cell apoptosis, as revealed by caspase-3 activation and DNA laddering. In particular, CF treated cells showed decrease HIF-1 levels and reduce GLUT-1 expression as in comparison with untreated cells. At the very same time, CF was able to decrease LDH activity and, consequently, the volume of lactate released within the extracellular atmosphere. Conclusions: We supplied evidence for an antiproliferative impact of CF on leukemia cell lines by inducing cell death by means of an apoptotic mechanism and by altering cancer cell metabolism by way of HIF-1 and GLUT-1 regulation. Because of its antioxidative and proapoptotic properties, CF could be a very good candidate for cancer prevention. Keyword phrases: Apoptosis, CellfoodTM, Glucose transporter 1, Hypoxia inducible factor 1 alpha, Lactate dehydrogenase, Leukemic cells, Tumor metabolismBackground Cell proliferation, that represents the essence of cancer illness, involves not just a deregulated manage of cell cycle but in addition adjustments of energy metabolism so as to fuel cell development and division. In actual fact, proliferation of cancer cells is accompanied by glycolysis activation and this altered glucose metabolism is one of the* Correspondence: [email protected] 1 Department of Biomolecular Sciences, Section of Clinical Biochemistry and Cellular Biology, University of Urbino “Carlo Bo”, By way of Ubaldini 7, 61029 Urbino, PU, Italy Full list of author information and facts is obtainable in the end on the articlemost common hallmark of cancer [1,2]. Roughly 60 to 90 of cancers show a metabolic profile, the so-called Warburg phenotype, characterized by their dependence upon glycolysis because the major supply of power, irrespective with the oxygen level [3]. In accordance with the Warburg impact, cancer cells up-regulate glucose transporters, notably GLUT-1, and convert pyruvate, the end-product of glycolysis, into lactate by lactate dehydrogenase (LDH), instead of oxidizing it in mitochondria [4-6]. In this context, the hypoxia inducible factor 1 (HIF-1) has been shown to play a fundamental part [7,8]. HIF-1 can be a transcription factor that consists of an O2-regulated?2013 Catalani et al.4-(Difluoromethyl)-3-fluorobenzoic acid Chemscene ; licensee BioMed Central Ltd.Buy178432-48-9 That is an Open Access post distributed under the terms from the Inventive Commons Attribution License (http://creativecommons.PMID:23819239 org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, supplied the original operate is correctly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies towards the data made accessible in this report, unless otherwise stated.Catalani et al. Journal of Experimental Clinical Cancer Investigation 2013, 32:63 http://jeccr/content/32/1/Page two ofHIF-1 as well as a constitutively expressed HIF-1 subunit. In cancer cells, HIF-1 is up-regulated and, in.