Tracking the Biochemistry of Cancer Cells and Dynamics of Physical Systems Using Nuclear Magnetic Resonance

Nuclear magnetic resonance (NMR) spectroscopy, providing a versatile technique for analyzing cancer metabolism based on 13C NMR analysis, is one of the most important tools for biological and more specifically cancer study purposes. The chemical shifts for 13C nuclei in organic molecules are spread out up to 200 ppm, enabling signal from each carbon in a compound be seen as a distinct peak. The relatively weak signals obtained from the NMR spectroscopy enables probing sensitive physical systems such as living systems without significantly disturbing them. In this dissertation, we have tracked 13C metabolism in different type of cancers, specially Glioblastoma Multiforme (GBM). GBM is an aggressive type of the Central Nervous System (CNS) tumor that grows within the brain tissue. In this study, we have investigated how the individually used fructose and glucose sugars and there combinations as high fructose corn syrup (HFCS) are metabolized in cultured SFxL glioblastoma and Huh-7 hepatocellular carcinoma cells as probed by 13C NMR spectroscopy. To understand more about cancer metabolism we did more study in glycolysis activity and pentose phosphate pathway (PPP). We used [1,2-13C] glucose to investigate the amount of lactate that could be produced from glycolysis versus PPP as the alternative route. Furthermore, we have investigated the metabolism of [1,2-13C] glucose with inhibitors of Lactate dehydrogenase A (LHDA) and sodium oxamate in GBM cells. LDHA is an important enzyme that is active in most of tissues. LDHA catalyzes the reversible conversion of pyruvate to lactate. Moreover, we have investigated the spin-lattice relaxation time (T1) of water-glycerol mixtures at the earth magnetic field. The water 1H T1s at various ratios of water-glycerol contents were measured at different temperatures ranging from 253.15 K to 353.15 K. In summary, this PhD dissertation presents and discusses a unique tool for deciphering cancer metabolism in vitro using NMR spectroscopy.