Pentose phosphate pathway alterations in multi-drug resistant leukemic T-cells: 31P NMR and enzymatic studies.
31P NMR studies were carried out on the parental drug-sensitive human T-lymphoblastoid cell line CCRI-CEM (CEM) and its multi-drug-resistant (MDR) CEM-VBL100 variants, to assess the role of the pentose phosphate (PP) in MDR expression. CEM and CEM-VBL100 were incubated in the presence of 2-deoxyglucose, as recently proposed by our group (Clin. Chim. Acta 208: 39, 1992). Accumulation of 2-deoxyglucose 6-phosphate was much lower in the drug-resistant than in sensitive cells, indicating PP shunt activation in the MDR variants. This result was confirmed by enzymatic analyses, which demonstrated that, with respect to the parental line, the MDR variant was characterized by a) unaltered hexokinase activity; b) higher glucose 6-phosphate dehydrogenase activity; c) increased levels of reduced glutathione and marked increase of glutathione peroxidase activity after cell exposure to an oxidizing agent (tert-butylhydroperoxide). These results support the view that cell detoxification mechanisms mediated by the pentose phosphate pathway may contribute to the expression of MDR in tumours.
Ferretti
A
A
Laboratory of Cellular Biology, Istituto Superiore di Sanità, Rome, Italy.
Chen
L L
LL
Di Vito
M
M
Barca
S
S
Tombesi
M
M
Cianfriglia
M
M
Bozzi
A
A
Strom
R
R
Podo
F
F
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000032:analysis / Q000096:biosynthesis; D003609:Dactinomycin / Q000633:toxicity; D004317:Doxorubicin / Q000633:toxicity; D004351:Drug Resistance / Q000235:genetics / Q000502:physiology*; D014644:Genetic Variation; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives*; D005958:Glucosephosphates / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008562:Membrane Glycoproteins / Q000032:analysis / Q000096:biosynthesis; D010427:Pentose Phosphate Pathway; D010758:Phosphorus; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma; D013601:T-Lymphocytes; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000633:toxicity
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D005958:Glucosephosphates; D008562:Membrane Glycoproteins; D003609:Dactinomycin; D010758:Phosphorus; C015785:2-deoxyglucose-6-phosphate; D019298:Glucose-6-Phosphate; D014747:Vinblastine; D004317:Doxorubicin