H(2)O(2)-mediated cytotoxicity of pharmacologic ascorbate concentrations to neuroblastoma cells: potential role of lactate and ferritin.

By intravenous (but not oral) application of ascorbate, millimolar serum concentrations can be reached, which are preferentially cytotoxic to cancer cells. Cytotoxicity is mediated by transition metal-dependent generation of H(2)O(2) in the interstitial space. In this study, the sensitivity of neuroblastoma cells (Kelly, SK-N-SH) to ascorbate and H(2)O(2) and their defense mechanisms against H(2)O(2) were investigated. Since aerobic glycolysis (the Warburg effect) is a feature of many tumour cells, their glucose consumption and lactate production were monitored. Furthermore, synthesis and release of ferritin by neuroblastoma cells were analysed in order to examine whether ferritin is possibly an iron source for H(2)O(2) generation. Ascorbate (0.6-5.0 mM) and H(2)O(2) (25-100 muM) were found to be similarly cytotoxic to Kelly and SK-N-SH cells. In each case, cytotoxicity increased if cell concentrations decreased, in accordance with low cell concentrations having lower capacities to detoxify H(2)O(2). Kelly and SK-N-SH cells produced and released remarkable amounts of lactate and ferritin. We propose the selective cytotoxicity of high dose ascorbate to tumour cells to be due to the preferential generation of H(2)O(2) in the acidic and ferritin-rich tumour microenvironment, combined with reduced defense systems against H(2)O(2) as a consequence of aerobic glycolysis.

Differential effects of tomato (Lycopersicon esculentum mill) matrix on the volatility of important aroma compounds.

Significant tomato matrix effects on the volatility of certain fresh tomato odorants were found. The concentrations of odorants such as (E,E)-2,4-decadienal, beta-damascenone, and beta-ionone, in crushed fresh tomato fruit obtained by solid-phase microextraction (SPME), resulting from a tomato matrix calibration curve were 5.5-, 2-, and 12-fold higher, respectively, than those calculated by calibration based on buffer solutions. Static headspace analyses indicated that, in most cases, the tomato matrix significantly retains the odorants relative to the buffer solution. Thus, the concentration of odorants in the headspace of tomato is lower than expected compared to a simple matrix such as buffer. CaCl(2), although needed in crushed fruit tissue to block enzymatic activity, was found to interact specifically with 2-isobutylthiazole, reducing its content in the headspace by at least 6-fold. If a matrix effect is found, analysis of the odorant molecule contents in the headspace rather than in the food is recommended in order to better evaluate their access to the olfactory receptors.