Amino acid metabolism as a therapeutic target in cancer: a review

Malignant cells often demonstrate a proliferative advantage when compared to non-malignant cells. However, the rapid growth and metabolism required for survival can also highlight vulnerabilities specific to these malignant cells. One such vulnerability exhibited by cancer is an increased demand for amino acids (AAs), which often results in a dependency on exogenous sources of AAs or requires upregulation of de novo synthesis. These metabolic alterations can be exploited by therapy, which aims to improve treatment outcome and decrease relapse and reoccurrence. One clinically utilised strategy targeting AA dependency is the use of asparaginase in the treatment of acute lymphoblastic leukaemia (ALL), which results in a depletion of exogenous asparagine and subsequent cancer cell death. Examples of other successful strategies include the exploitation of arginine deiminase and methioninase, nutrient restriction of methionine and the inhibition of glutaminase. In this review, we summarise these treatment strategies into three promising avenues: AA restriction, enzymatic depletion and inhibition of metabolism. This review provides an insight into the complexity of metabolism in cancer, whilst highlighting these three current research avenues that have support in both preclinical and clinical settings.

An imaging approach for determining the mechanism of enhancement of intestinal absorption of an L-theanine supplement

Background & objective Theanine (L-glutamylethylamide) contained in green tea is a functional food component that has been attracting attention due to its relaxation effect. It was shown that the ingredients added to the theanine formulations increased the absorption of theanine. If this mechanism can be elucidated, it would be possible to contribute to development of evidence-based formulations. In this study, we investigated the effect of ingredients in the formulations on the absorption of theanine in detail. Main methods After oral administration of a mixture of theanine and additional components to Wistar rats the plasma concentration was determined by an HPLC and the pharmacokinetic parameters were calculated. In addition, a new system for evaluating intestinal blood flow was developed since the involvement of intestinal blood flow was considered as a factor that increased absorption of theanine. Key findings Plasma concentration of theanine increased significantly in the combined use group with eight ingredients containing piperine as compared with theanine only group. Piperine would increase theanine absorption by increased blood flow, not an inhibition of metabolism. We succeeded to develop a visual and quantitative system to evaluate the effect of these ingredients directly including piperine on the intestinal blood flow using indocyanine green while maintaining physiological conditions. Significance Increased intestinal blood flow by these ingredients including piperine enhanced the absorption of theanine. Other mechanisms may also be considered as the mechanism by which theanine absorption is increased in addition to increased blood flow.

Bacterial Toxicity of Functionalized Polystyrene Latex Nanoparticles Toward Escherichia coli

Nanotechnology has the potential to produce a variety of new materials in the coming years, as a result of the design of novel nanoparticles with new physicochemical characteristics. However, their potential to adversely affect the environment and human health must be addressed. The toxicity of polystyrene latex (PSL) nanoparticles with various functional groups toward Escherichia coli KP7600 strain was investigated using the colony count method, and confocal microscopy observations. It was found that the positively charged PSL nanoparticles led to the death of the bacterial cells. Confocal observations of the bacterial cells after 1 h of exposure to the amine-modified, positively-charged PSL nanoparticles in an aqueous NaCl solution showed that the surfaces of the dead cells were almost entirely covered with the nanoparticles. No uptake of the nanoparticles into the bacterial cells was observed, regardless of the cell viability. It is likely that the adhesion of the positively charged nanoparticles onto the surface of the bacterial cells (due to the electrostatic attractive force) caused a decrease in the fluidity of the cell membrane, and the inhibition of metabolism through the cell membrane led to the death of the bacterial cells.