A Selective Competitive Inhibitor of Aldehyde Dehydrogenase 1A3 Hinders Cancer Cell Growth, Invasiveness and Stemness In Vitro.

Aldehyde dehydrogenase 1A3 (ALDH1A3) belongs to an enzymatic superfamily composed by 19 different isoforms, with a scavenger role, involved in the oxidation of a plethora of aldehydes to the respective carboxylic acids, through a NAD+-dependent reaction. Previous clinical studies highlighted the high expression of ALDH1A3 in cancer stem cells (CSCs) correlated to a higher risk of cancer relapses, chemoresistance and a poor clinical outcome. We report on the structural, biochemical, and cellular characterization of NR6, a new selective ALDH1A3 inhibitor derived from an already published ALDH non-selective inhibitor with cytotoxic activity on glioblastoma and colorectal cancer cells. Crystal structure, through X-Ray analysis, showed that NR6 binds a non-conserved tyrosine residue of ALDH1A3 which drives the selectivity towards this isoform, as supported by computational binding simulations. Moreover, NR6 shows anti-metastatic activity in wound healing and invasion assays and induces the downregulation of cancer stem cell markers. Overall, our work confirms the role of ALDH1A3 as an important target in glioblastoma and colorectal cells and propose NR6 as a promising molecule for future preclinical studies.

Palatability and stability of shortbread made with low saturated fat content.

High consumption of saturated fatty acids (SFA) is associated with increased risk of cardiovascular disease and the European Food Safety Agency has called for lower SFA intake. This study assessed the formulation of low SFA shortbreads by replacing 60% and 70% of the butter content with high oleic sunflower oil and water. The quality of the low SFA shortbreads was evaluated through acidity, peroxide value, moisture, ash content, water activity, pH, protein, fat content, and fatty acid profiles. A sensory evaluation was performed to ascertain the effect on flavor. Stability of the new formulations was assessed by conducting accelerated shelf-life studies. The high oleic sunflower oil replacement of butter at levels of 60% and 70% decreased the final SFA content by 52% and 61%, respectively. On the other hand, monounsaturated fat content increased 55% on average while polyunsaturated fat content increased by 40%. Furthermore the new formulations possess quality parameters similar to those of traditional shortbreads (TSs). The study of the shelf life of the products showed that there are no significant variations in peroxide values, malondialdehyde content, or fatty acid profiles in biscuits over time, confirming their high stability. The quantitative descriptive analysis showed that the TS and low SFA shortbreads have similar sensory profiles, and the consumer tests indicated that the low SFA shortbreads were well liked.