Spectroscopic and Chemometric Investigations into the Modes of Action of Anti-Diabetic and Anti-Cancer Drugs

Abstract

Metabolic disorders such as Diabetes Mellitus, as a result of added sugars in form of fructose in the Western diet, are reaching epidemic proportions and better understanding on how to treat individuals with such disorders is required. The use of vanadium-derived complexes as dietary supplements offers one such approach due to their purported antidiabetic and anti-cancer effects; however, their mode(s) of action are still not completely understood. Fourier-transform infrared (FTIR) microspectroscopy/imaging in combination with Chemometrics was used to gain insights into biochemical changes induced by sugars and vanadium treatments at the cellular level. The insulin-responsive cell lines 3T3-L1 mouse adipocyte and HepG2 (hepatocarcinoma) were used as they are representative models of diabetes and its complications. Interpretation of results revealed that vanadate-fructose treatments increased oxidative stress in all cell types and resulted in apoptotic pathways that were characterised by lipid synthesis and peroxidation, resulting in lipotoxicity. Increased cell viability at low vanadate concentration and glucose resulted in protein synthesis rather than de novo lipid synthesis. At higher concentrations of vanadate, protein aggregation and the possible transition of HepG2 cells from an epithelial to a mesenchymal phenotype occurred. These cells may revert back to an epithelial phenotype when treated with normal supplemented media. Synchrotron and laboratory based hyperspectral imaging studies revealed common biochemical processes in adipocytes associated with all treatments, where various membrane and interior lipid compositions partitioned and lipid/fatty acid compartmentalisation was observed in chemical images, providing insights into the way these cells store lipids and fatty acids into specialised compartments.