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Published on: January 11, 2019
Methionine restriction reduces the chemosensitivity of central nervous system tumour cell lines
N Najim1, I D Podmore, A McGown
1Kidscan Children's Cancer Research Centre, Biomedical Sciences Research Institute, School of Environment and Life Sciences, University of Salford, Salford M54WT, UK.
Background:
The aim of this study was to investigate the effects of methionine depletion with cytotoxic agents that are potentially influenced by depletion of methionine, and are known to have a role in CNS tumour treatments for children.
Materials And Methods:
Cytotoxicity studies and synergistic interactions were assayed by SRB assay. Glutathione levels were assayed by HPLC after derivatization with OPA. MGMT activity was determined by a restriction endonuclease inhibition assay.
Results:
Methionine depletion causes a demonstrable increase in glutathione levels for medulloblastoma (Daoy) and glioma (D54) cells, with a decrease in MGMT activity for Daoy cells. For both cell lines, methionine depletion reduces their sensitivity to a range of chemotherapy agents that interface at the level of methionine metabolism, namely temozolomide, cisplatin and methotrexate.
Conclusion:
The results show that methionine depletion increases the resistance of tumour cells to the chemotherapeutic agents tested. However, in methionine-replete conditions, we have demonstrated synergistic activity for various combinations of chemotherapeutic agents that are hitherto unreported and may have clinical utility for the treatment of children with CNS tumours.
