Abstract
Metabolic profiles of hydrophilic and lipophilic cell extracts from three cancer cell lines, Miapaca-2, Panc-1 and AsPC-1, and a non-cancerous pancreatic ductal epithelial cell line, H6C7, were examined by proton nuclear magnetic resonance spectroscopy. Over twenty five hydrophilic metabolites were identified by principal component and statistical significance analyses as distinguishing the four cell types. Fifteen metabolites were identified with significantly altered concentrations in all cancer cells, e.g. absence of phosphatidylgrycerol and phosphatidylcholine, and increased phosphatidylethanolamine and cholesterols. Altered concentrations of metabolites involved in glycerophospholipid metabolism, lipopolysaccharide and fatty acid biosynthesis indicated differences in cellular membrane composition between non-cancerous and cancer cells. In addition to cancer specific metabolites, several metabolite changes were unique to each cancer cell line. Increased N-acetyl groups in AsPC-1, octanoic acids in Panc-1, and UDP species in Miapaca-2 indicated differences in cellular membrane composition between the cancer cell lines. Induced glutamine metabolism and protein synthesis in cancer cells were indicated by absence of glutamine other metabolites such as acetate, lactate, serine, branched amino acids, and succinate. Knowledge of the specifically altered metabolic pathways identified in these pancreatic cancer cell lines may be useful for identifying new therapeutic targets and studying the effects of potential new therapeutic drugs.
Highlights
Pancreatic cancer is one of the most lethal human cancers
Several metabolites involved in glycerophospholipid metabolism, lipopolysaccharide biosynthesis, fatty acid biosynthesis, and N-acetyl glycoprotein/glycolipids metabolism were different between all cancer cell types and non-cancerous H6C7 cells indicating differences in cellular membrane composition in highly proliferative cells
Increased levels of cholesterol and polysaturated fatty acids were observed in all cancer cells, suggesting the presence of higher membrane fluidity in pancreatic cancer cells compared to normal cells
Summary
Pancreatic cancer is one of the most lethal human cancers. According to the cancer statistics from 2010, more than 40 thousand patients are expected to be diagnosed in coming year [1]. Pancreatic cancer has the lowest five-year survival rate among all types of cancers. Most diagnoses occur after the cancer has progressed to an advanced stage when a surgical cure is not feasible. Tomography scans, endoscopic ultrasound and endoscopic retrograde cholangiopancreatography are some of the current detection and diagnostic methods for pancreatic cancer [2,3]. These methods are highly invasive and not suitable for general population screening. Development of an early detection method for pancreatic cancer is essential in order to improve the likelihood that diagnosis will occur before the cancer is at a stage that is too advanced to treat
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