Many byproducts and wastes generated by agroindustries contain polyphenols with potential application as food antioxidants and preventive agents against skin cancer and other diseases. The performance of polyphenolic fractions from Parellada grape (Vitis vinifera) pomace as antioxidants in different physicochemical environments was tested. Fractions containing oligomers with mean degree of polymerization between 3 and 4 and percentage galloylation ca. 30% were the most potent free radical scavengers and efficient antioxidants in an oil-in-water emulsion. A fraction including glycosylated flavonols was also efficient in the emulsion. All the fractions showed low aquatic toxicity and weak influence on proliferation of human melanoma cells.

Metabolic control analysis (MCA) provides a quantitative description of substrate flux in response to changes in system parameters of complex enzyme systems. Medical applications of the approach include the following: understanding the threshold effect in the manifestation of metabolic diseases; investigating the gene dose effect of aneuploidy in inducing phenotypic transformation in cancer; correlating the contributions of individual genes and phenotypic characteristics in metabolic disease (e.g., diabetes); identifying candidate enzymes in pathways suitable as targets for cancer therapy; and elucidating the function of "silent" genes by identifying metabolic features shared with genes of known pathways. MCA complements current studies of genomics and proteomics, providing a link between biochemistry and functional genomics that relates the expression of genes and gene products to cellular biochemical and physiological events. Thus, it is an important tool for the study of genotype-phenotype correlations. It allows genes to be ranked according to their importance in controlling and regulating cellular metabolic networks. We can expect that MCA will have an increasing impact on the choice of targets for intervention in drug discovery.

Thiamine deficiency frequently occurs in patients with advanced cancer and therefore thiamine supplementation is used as nutritional support. Thiamine (vitamin B1) is metabolized to thiamine pyrophosphate, the cofactor of transketolase, which is involved in ribose synthesis, necessary for cell replication. Thus, it is important to determine whether the benefits of thiamine supplementation outweigh the risks of tumor proliferation. Using oxythiamine (an irreversible inhibitor of transketolase) and metabolic control analysis (MCA) methods, we measured an in vivo tumour growth control coefficient of 0.9 for the thiamine-transketolase complex in mice with Ehrlich's ascites tumour. Thus, transketolase enzyme and thiamine clearly determine cell proliferation in the Ehrlich's ascites tumour model. This high control coefficient allows us to predict that in advanced tumours, which are commonly thiamine deficient, supplementation of thiamine could significantly increase tumour growth through transketolase activation. The effect of thiamine supplementation on tumour proliferation was demonstrated by in vivo experiments in mice with the ascites tumour. Thiamine supplementation in doses between 12.5 and 250 times the recommended dietary allowance (RDA) for mice were administered starting on day four of tumour inoculation. We observed a high stimulatory effect on tumour growth of 164% compared to controls at a thiamine dose of 25 times the RDA. This growth stimulatory effect was predicted on the basis of correction of the pre-existing level of thiamine deficiency (42%), as assayed by the cofactor/ enzyme ratio. Interestingly, at very high overdoses of thiamine, < 2500 times the RDA, thiamine supplementation had the opposite effect and caused 10% inhibition of tumour growth. This effect was heightened, resulting in a 36% decrease, when thiamine supplementation was administered from the 7th day prior to tumour inoculation. Our results show that thiamine supplementation sufficient to correct existing thiamine deficiency stimulates tumour proliferation as predicted by MCA. The tumour inhibitory effect at high doses of thiamine is unexplained and merits further study.Keywords: transketolase; thiamine; Ehrlich's ascites tumour; metabolic control analysis.One of the most disturbing facts about cancer is that prevalence rates are still rising despite the resources that have been developed over the last three decades for understanding and controlling it more efficiently [1]. Cancer is currently seen as a complex genetic phenomenon characterized by breakdown in the integrity or function of cellular growth-regulating genes and their signalling pathways [2,3]. The increasing worldwide cancer epidemic raises the need for novel approaches to treating it, not only as a genetic abnormality but also as a metabolic disease. As tumour cells are metabolically unbalanced with respect to surrounding tissue, an alternative approach to new cancer drug development is the analysis of metabolic reaction network in tumour cells and determining the contr...