Mn bioavailability by polarized Caco-2 cells: comparison between Mn gluconate and Mn oxyprolinate

<p>Abstract</p> <p>Background</p> <p>Micronutrient inadequate intake is responsible of pathological deficiencies and there is a need of assessing the effectiveness of metal supplementation, frequently proposed to rebalance poor diets. Manganese (Mn) is present in many enzymatic intracellular systems crucial for the regulation of cell metabolism, and is contained in commercially available metal supplements.</p> <p>Methods</p> <p>We compared the effects of two different commercial Mn forms, gluconate (MnGluc) and oxyprolinate (MnOxP). For this purpose we used the polarized Caco-2 cells cultured on transwell filters, an established in vitro model of intestinal epithelium. Since micronutrient deficiency may accelerate mitochondrial efficiency, the mitochondrial response of these cells, in the presence of MnGluc and MnOxP, by microscopy methods and by ATP luminescence assay was used.</p> <p>Results</p> <p>In the presence of both MnOxP and MnGluc a sustained mitochondrial activity was shown by mitoTraker labeling (indicative of mitochondrial respiration), but ATP intracellular content remained comparable to untreated cells only in the presence of MnOxP. In addition MnOxP transiently up-regulated the antioxidant enzyme Mn superoxide dismutase more efficiently than MnGluc. Both metal treatments preserved NADH and βNADPH diaphorase oxidative activity, avoided mitochondrial dysfunction, as assessed by the absence of a sustained phosphoERK activation, and were able to maintain cell viability.</p> <p>Conclusions</p> <p>Collectively, our data indicate that MnOxP and MnGluc, and primarily the former, produce a moderate and safe modification of Caco-2 cell metabolism, by activating positive enzymatic mechanisms, thus could contribute to long-term maintenance of cell homeostasis.</p

Cancer metabolism: current perspectives and future directions

Cellular metabolism influences life and death decisions. An emerging theme in cancer biology is that metabolic regulation is intricately linked to cancer progression. In part, this is due to the fact that proliferation is tightly regulated by availability of nutrients. Mitogenic signals promote nutrient uptake and synthesis of DNA, RNA, proteins and lipids. Therefore, it seems straight-forward that oncogenes, that often promote proliferation, also promote metabolic changes. In this review we summarize our current understanding of how ‘metabolic transformation' is linked to oncogenic transformation, and why inhibition of metabolism may prove a cancer′s ‘Achilles' heel'. On one hand, mutation of metabolic enzymes and metabolic stress sensors confers synthetic lethality with inhibitors of metabolism. On the other hand, hyperactivation of oncogenic pathways makes tumors more susceptible to metabolic inhibition. Conversely, an adequate nutrient supply and active metabolism regulates Bcl-2 family proteins and inhibits susceptibility to apoptosis. Here, we provide an overview of the metabolic pathways that represent anti-cancer targets and the cell death pathways engaged by metabolic inhibitors. Additionally, we will detail the similarities between metabolism of cancer cells and metabolism of proliferating cells