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Magnetic resonance detects metabolic changes associated with chemotherapy-induced apoptosis
- Source :
- British journal of cancer, vol 80, iss 7, British Journal of Cancer
- Publication Year :
- 1999
- Publisher :
- Springer Science and Business Media LLC, 1999.
-
Abstract
- Apoptosis was induced by treating L1210 leukaemia cells with mechlorethamine, and SW620 colorectal cells with doxorubicin. The onset and progression of apoptosis were monitored by assessing caspase activation, mitochondrial transmembrane potential, phosphatidylserine externalization, DNA fragmentation and cell morphology. In parallel, 31P magnetic resonance (MR) spectra of cell extracts were recorded. In L1210 cells, caspase activation was detected at 4 h. By 3 h, the MR spectra showed a steady decrease in NTP and NAD, and a significant build-up of fructose 1,6-bisphosphate (F-1,6-P) dihydroxyacetonephosphate and glycerol-3-phosphate, indicating modulation of glycolysis. Treatment with iodoacetate also induced a build-up of F-1,6-P, while preincubation with two poly(ADP-ribose) polymerase inhibitors, 3-aminobenzamide and nicotinamide, prevented the drop in NAD and the build-up of glycolytic intermediates. This suggested that our results were due to inhibition of glyceraldehyde-3-phosphate dehydrogenase, possibly as a consequence of NAD depletion following poly(ADP-ribose) polymerase activation. Doxorubicin treatment of the adherent SW620 cells caused cells committed to apoptosis to detach. F-1,6-P was observed in detached cells, but not in treated cells that remained attached. This indicated that our observations were not cell line- or treatment-specific, but were correlated with the appearance of apoptotic cells following drug treatment. The 31P MR spectrum of tumours responding to chemotherapy could be modulated by similar effects. © 1999 Cancer Research Campaign
- Subjects :
- Cancer Research
Magnetic Resonance Spectroscopy
Apoptosis
chemotherapy
Cell morphology
Tumor Cells, Cultured
Fructosediphosphates
2.1 Biological and endogenous factors
Aetiology
Leukemia L1210
Caspase
Cancer
Cultured
biology
apoptosis
Regular Article
glycolysis
poly(ADP-ribose) polymerase
Tumor Cells
magnetic resonance spectroscopy (MRS)
Oncology
Biochemistry
5.1 Pharmaceuticals
Dihydroxyacetone Phosphate
6.1 Pharmaceuticals
Caspases
Glycerophosphates
Benzamides
Public Health and Health Services
DNA fragmentation
Development of treatments and therapeutic interventions
Colorectal Neoplasms
Niacinamide
Programmed cell death
Cell Survival
Oncology and Carcinogenesis
Iodoacetates
Antineoplastic Agents
Animals
Humans
Mechlorethamine
Oncology & Carcinogenesis
Evaluation of treatments and therapeutic interventions
NAD
Molecular biology
Doxorubicin
Cell culture
biology.protein
L1210 cells
NAD+ kinase
Digestive Diseases
poly(ADP-ribose) polymerase (PARP)
Subjects
Details
- ISSN :
- 15321827 and 00070920
- Volume :
- 80
- Database :
- OpenAIRE
- Journal :
- British Journal of Cancer
- Accession number :
- edsair.doi.dedup.....755bf36a0172b0c685f95ef6f50daa20