Enhanced Citrate Synthase Activity in Human Pancreatic Cancer

Objectives: Assuming that a high flux of carbohydrate is strictly connected with lipid synthesis in neoplastic cells, one can hypothesize that the activity of citrate synthase, which plays an important role in glucose to lipid conversion, is enhanced in pancreatic cancer. The aim of the present study was to verify this hypothesis. Methods: The activity of citrate synthase (as well as lactate and glucose 6-phosphate dehydrogenases) was measured using tissue extract prepared from specimens (pancreatic cancer and control specimens taken from the adjacent pancreatic normal tissue) obtained from 24 patients with ductal carcinoma who underwent pancreatoduodenectomy or total pancreatomy. Results: The average of citrate synthase activity in human pancreatic ductal carcinoma is significantly higher comparing with adjacent nonneoplastic tissue: 40.2 ± 27.2 and 18.3 ± 13.6 nmole/min/mg protein, respectively (P = 0.001). The lactate dehydrogenase and glucose 6-phosphate dehydrogenase activity in human pancreatic ductal carcinoma were also higher than in adjacent nonneoplastic tissues. Conclusion: It is likely that enhanced citrate synthase activity contributes to the conversion of glucose to lipids in pancreatic cancer providing substrate for membrane lipids synthesis.

[1]  S. Piantadosi,et al.  Haptoglobin-related protein (Hpr) epitopes in breast cancer as a predictor of recurrence of the disease. , 1989, The New England journal of medicine.

[2]  L. Jacobs,et al.  Fatty acid synthesis: a potential selective target for antineoplastic therapy. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[3]  T. Tang,et al.  Human glucose‐6‐phosphate dehydrogenase (G6PD) gene transforms NIH 3T3 cells and induces tumors in nude mice , 2000, International journal of cancer.

[4]  A. Rashid,et al.  Elevated expression of fatty acid synthase and fatty acid synthetic activity in colorectal neoplasia. , 1997, The American journal of pathology.

[5]  G. Semenza,et al.  Oncogenic alterations of metabolism. , 1999, Trends in biochemical sciences.

[6]  M. Cascante,et al.  Oxythiamine and dehydroepiandrosterone induce a G1 phase cycle arrest in Ehrlich's tumor cells through inhibition of the pentose cycle , 1999, FEBS letters.

[7]  S. Jackowski,et al.  Activity of the phosphatidylcholine biosynthetic pathway modulates the distribution of fatty acids into glycerolipids in proliferating cells. , 2000, Biochimica et biophysica acta.

[8]  D. Mayer,et al.  Hepatocellular glycogenosis and hepatocarcinogenesis. , 1980, Biochimica et biophysica acta.

[9]  S. Jackowski Coordination of membrane phospholipid synthesis with the cell cycle. , 1994, The Journal of biological chemistry.

[10]  L. Baert,et al.  Selective activation of the fatty acid synthesis pathway in human prostate cancer , 2000, International journal of cancer.

[11]  G. Weber Enzymology of cancer cells (second of two parts). , 1977, The New England journal of medicine.

[12]  J. Świerczyński,et al.  Intracellular distribution of fumarase in rat skeletal muscle. , 1983, Biochimica et biophysica acta.

[13]  T. Pretlow,et al.  Glucose‐6‐phosphate dehydrogenase: A possible clinical indicator for prostatic carcinoma , 1982, Cancer.

[14]  R. Kurman,et al.  Fatty acid synthase expression in endometrial carcinoma , 1998, Cancer.

[15]  P. Visca,et al.  Expression of fatty acid synthase (FAS) as a predictor of recurrence in stage I breast carcinoma patients , 1996, Cancer.

[16]  Marta Martínez,et al.  Alteration of the bioenergetic phenotype of mitochondria is a hallmark of breast, gastric, lung and oesophageal cancer. , 2004, The Biochemical journal.

[17]  S. Bassilian,et al.  Isotopomer study of lipogenesis in human hepatoma cells in culture: contribution of carbon and hydrogen atoms from glucose. , 1995, Analytical biochemistry.

[18]  Kathy Pfeiffer,et al.  Low mitochondrial respiratory chain content correlates with tumor aggressiveness in renal cell carcinoma. , 2002, Carcinogenesis.

[19]  M. Cascante,et al.  Transforming growth factor beta2 promotes glucose carbon incorporation into nucleic acid ribose through the nonoxidative pentose cycle in lung epithelial carcinoma cells. , 2000, Cancer research.

[20]  P. Visca,et al.  Immunohistochemical study of fatty acid synthase in ovarian neoplasms. , 2000, Oncology reports.

[21]  L. Boros,et al.  Genistein Inhibits Nonoxidative Ribose Synthesis in MIA Pancreatic Adenocarcinoma Cells: A New Mechanism of Controlling Tumor Growth , 2001, Pancreas.

[22]  M Cascante,et al.  Wheat Germ Extract Decreases Glucose Uptake and RNA Ribose Formation but Increases Fatty Acid Synthesis in MIA Pancreatic Adenocarcinoma Cells , 2001, Pancreas.

[23]  C. Chiodino,et al.  Enhancement of cholesterol synthesis and pentose phosphate pathway activity in proliferating hepatocyte nodules. , 1985, Carcinogenesis.

[24]  M Cascante,et al.  Gleevec (STI571) influences metabolic enzyme activities and glucose carbon flow toward nucleic acid and fatty acid synthesis in myeloid tumor cells. , 2001, The Journal of biological chemistry.

[25]  S. Jackowski Cell Cycle Regulation of Membrane Phospholipid Metabolism* , 1996, The Journal of Biological Chemistry.

[26]  M. Matuszewski,et al.  Increased activity of glycerol 3-phosphate dehydrogenase and other lipogenic enzymes in human bladder cancer. , 2003, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[27]  G. Peterson,et al.  A simplification of the protein assay method of Lowry et al. which is more generally applicable. , 1977, Analytical biochemistry.