![]()
|
|
||||||||
(Received for publication, October 12, 1995; and in revised form, December 7, 1995) The effect of 6-aminonicotinamide on the metabolism of RIF-1
tumor cells was investigated using
Volume 271,
Number 8,
Issue of February 23, 1996 pp. 4113-4119
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
C
and
P NMR Investigation of Effect of 6-Aminonicotinamide
on Metabolism of RIF-1 Tumor Cells in Vitro
C and
P
NMR spectroscopy. 6-Aminonicotinamide can be metabolized to
6-amino-NAD(P), a competitive inhibitor of NAD(P)-requiring processes.
40 µM 6-aminonicotinamide led to an inhibition of
6-phosphogluconate dehydrogenase and an accumulation of
6-phosphogluconate. A subsequent accumulation of the 6-phosphogluconate
precursor 6-phosphoglucono-
-lactone was observed in the
C NMR spectrum. These metabolites were shown to be
intracellular, although a small amount of leakage of
6-phosphoglucono-
-lactone occurred. The intracellular
concentrations of 6-phosphogluconate and 6-phosphoglucono-
-lactone
were 1.9 ± 0.8 µmol/10
cells (±1 standard
deviation) and 0.8 ± 0.4 µmol/10
cells,
respectively, after 15 h. Glucose utilization and lactate production
were significantly inhibited by 6-aminonicotinamide (both p < 0.05), indicating inhibition of glycolysis. P
NMR data showed that phosphocreatine was significantly depleted in
cells exposed to 6-aminonicotinamide (p < 0.05). Exposure
of RIF-1 cells to 6-aminonicotinamide prior to 3- or 6-Gy x-irradiation
induced a supra-additive cell kill, indicating that 6-aminonicotinamide
is acting as a radiosensitizer. There was no effect of
6-aminonicotinamide alone or when the drug was given postradiation,
suggesting that its mechanism of action may be by inhibition of
radiation-induced repair.
![]()
CiteULike
Complore
Connotea
Del.icio.us
Digg
Reddit
Technorati What's this?
This article has been cited by other articles:
![]() |
P. A. Nguewa, M. A. Fuertes, C. Alonso, and J. M. Perez Pharmacological Modulation of Poly(ADP-ribose) Polymerase-Mediated Cell Death: Exploitation in Cancer Chemotherapy Mol. Pharmacol., November 1, 2003; 64(5): 1007 - 1014. [Full Text] [PDF] |
||||
![]() |
D. S. Martin, J. R. Bertino, and J. A. Koutcher ATP Depletion + Pyrimidine Depletion Can Markedly Enhance Cancer Therapy: Fresh Insight for a New Approach Cancer Res., December 1, 2000; 60(24): 6776 - 6783. [Full Text] |
||||
![]() |
P. M. J. McSheehy, M. O. Leach, I. R. Judson, and J. R. Griffiths Metabolites of 2'-Fluoro-2'-deoxy-D-glucose Detected by 19F Magnetic Resonance Spectroscopy in Vivo Predict Response of Murine RIF-1 Tumors to 5-Fluorouracil Cancer Res., April 1, 2000; 60(8): 2122 - 2127. [Abstract] [Full Text] |
||||
![]() |
I. I. Budihardjo, S. A. Boerner, S. Eckdahl, P. A. Svingen, R. Rios, M. M. Ames, and S. H. Kaufmann Effect of 6-Aminonicotinamide and Other Protein Synthesis Inhibitors on Formation of Platinum-DNA Adducts and Cisplatin Sensitivity Mol. Pharmacol., March 1, 2000; 57(3): 529 - 538. [Abstract] [Full Text] |
||||
![]() |
W.-N. Tian, L. D. Braunstein, K. Apse, J. Pang, M. Rose, X. Tian, and R. C. Stanton Importance of glucose-6-phosphate dehydrogenase activity in cell death Am J Physiol Cell Physiol, May 1, 1999; 276(5): C1121 - C1131. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. M. Jorgensen, O. N. Jensen, H. U. Holst, J.-J. Hansen, T. J. Corydon, P. Bross, L. Bolund, and N. Gregersen Grp78 Is Involved in Retention of Mutant Low Density Lipoprotein Receptor Protein in the Endoplasmic Reticulum J. Biol. Chem., October 20, 2000; 275(43): 33861 - 33868. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Massillon Regulation of the Glucose-6-phosphatase Gene by Glucose Occurs by Transcriptional and Post-transcriptional Mechanisms. DIFFERENTIAL EFFECT OF GLUCOSE AND XYLITOL J. Biol. Chem., February 2, 2001; 276(6): 4055 - 4062. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |