Dietary factors and growth and metabolism in experimental tumors

• Published in: The Journal of nutritional biochemistry 2007-10, Vol.18 (10), p.637-649
• Main Authors: Sauer, Leonard A., Blask, David E., Dauchy, Robert T.
• Format: Article
• Language: English
• Subjects: Amino Acids - metabolism; animal models; Animals; anticarcinogenic activity; Biological and medical sciences; Blood Glucose - metabolism; CLA isomers; conjugated linoleic acid; diet; dietary fat; Dietary Fats, Unsaturated - administration & dosage; Dietary fish oil; disease prevention; docosahexaenoic acid; eicosapentaenoic acid; Feeding. Feeding behavior; fish oils; Fish Oils - administration & dosage; Fundamental and applied biological sciences. Psychology; health foods; Humans; Ketone Bodies - metabolism; Lactic Acid - metabolism; Linoleic acid; Linoleic Acid - metabolism; Linoleic Acids - metabolism; Linoleic Acids, Conjugated - pharmacology; Male; mechanism of action; Melatonin; Melatonin - physiology; n-3 Fatty acids; Neoplasm Transplantation; neoplasms; Neoplasms, Experimental - diet therapy; Neoplasms, Experimental - physiopathology; nutrition-genotype interaction; nutritional adequacy; nutritional intervention; omega-3 fatty acids; omega-6 fatty acids; optimal nutrition; Rats; Signal Transduction - drug effects; stereoisomers; Trans Fatty Acids - pharmacology; Transplantation, Heterologous; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 0955-2863; 1873-4847
• DOI: 10.1016/j.jnutbio.2006.12.009

Development of a diet that provides adequate nutrition and effective cancer prevention is an important goal in nutrition and cancer research. A confounding aspect of dietary control of tumor growth is the fact that some nutrients may up-regulate tumor growth, whereas other nutrients and nonnutrients down-regulate growth. Both up- and down-regulators may be present in the same foodstuff. Identification of these substances, determination of their mechanisms of action and potencies, as well as the interactions among the different mechanisms are topics of ongoing research. In this review, we describe results obtained in vivo or during perfusion in situ using solid tissue-isolated rodent tumors and human cancer xenografts in nude rats. Linoleic acid (LA), an essential n-6 polyunsaturated fatty acid (PUFA), was identified as an agent in dietary fat that is responsible for an up-regulation of tumor growth in vivo. Tumor LA uptake, mediated by high intratumor cAMP, stimulated formation of the mitogen, 13-hydroxyoctadecadienoic acid (13-HODE) and also increased ERK1/2 phosphorylation, [ 3H]thymidine incorporation and growth. A mechanism for control of this growth-promoting pathway was revealed during studies of the effects of dietary nutrients and nonnutrients known to inhibit tumor growth. These included four groups of lipophilic agents: n-3 fatty acids, melatonin, conjugated LA isomers and trans fatty acids. Each of these agents activated an inhibitory G protein-coupled receptor-mediated pathway that specifically suppressed tumor uptake of saturated, monounsaturated and n-6 PUFAs, thereby inhibiting an early step in the LA-dependent growth-promoting pathway.