RT Journal Article
SR Electronic
T1 Biochemical Changes and Cytotoxicity Associated with Methionine Depletion in Paediatric Central Nervous System Tumour Cell Lines
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 2971
OP 2976
VO 29
IS 8
A1 N. NAJIM
A1 I.D. PODMORE
A1 A. MCGOWN
A1 E.J. ESTLIN
YR 2009
UL http://ar.iiarjournals.org/content/29/8/2971.abstract
AB Background: The aim of this study was to investigate the importance of the extent and duration of methionine depletion as a cause of cytotoxicity for CNS tumour cell lines, and also to investigate the associated in vitro cellular biochemical responses. Materials and Methods: Cell growth inhibition was assayed by the SRB assay. Intracellular methionine levels were measured by GC/MS following dervatization with MTBSTFA. After methionine depletion, methionine synthase and MGMT activities were also determined. Glutathione levels were assayed by HPLC after derivatization with OPA. Results: Medulloblastoma (Daoy) and glioma (D54) cells were found to be methionine dependent and effects on proliferation, apoptosis and clonogenic survival were dependent on time and degree of methionine depletion. Methionine depletion also caused a demonstrable decrease in L-methionine levels and an increase in glutathione levels for both cell lines, with a decrease in MGMT activity for Daoy cells. Conclusion: Daoy and D54 cells are methionine dependent; the degree and duration of methionine depletion is related to cell death. The associated biochemical changes in MGMT and glutathione may be expected to modulate chemosensitivity and this will be investigated in future studies.