Glutathione levels are associated with methotrexate resistance in acute lymphoblastic leukemia cell lines.

ABSTRACT:

Introduction

Methotrexate (MTX), a folic acid antagonist and nucleotide synthesis inhibitor, is a cornerstone drug used against acute lymphoblastic leukemia (ALL), but its mechanism of action and resistance continues to be unraveled even after decades of clinical use.

Methods

To better understand the mechanisms of this drug, we accessed the intracellular metabolic content of 13 ALL cell lines treated with MTX by 1H-NMR, and correlated metabolome data with cell proliferation and gene expression. Further, we validated these findings by inhibiting the cellular antioxidant system of the cells in vitro and in vivo in the presence of MTX.

Results

MTX altered the concentration of 31 out of 70 metabolites analyzed, suggesting inhibition of the glycine cleavage system, the pen

SUBMITTER: Canevarolo RR 

PROVIDER: S-EPMC9751399 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature