Metabolic reprogramming is increasingly being viewed as a hallmark of
cancer. Accordingly, metabolic readouts can serve as
biomarkers of response to
therapy. The goal of this study was to investigate some of the MRS-detectable metabolic consequences of
mitogen-activated protein kinase kinase (
MEK) inhibition. We investigated PC3
prostate cancer, MCF-7
breast cancer and A375
melanoma cells, and determined that, consistent with previous studies, MRS-detectable levels of
phosphocholine decreased significantly in all cell lines (to 63%, 50% and 18% of the control, respectively) following
MEK inhibition with
U0126. This effect was mediated by a decrease in the expression of
choline kinase α, the
enzyme that catalyzes the phosphorylation of
choline. In contrast, the impact of
MEK inhibition on glycolysis was cell line dependent. A375 cells, which express mutant BRAF, demonstrated significant decreases in
glucose uptake (to 36% of control) and
lactate production (to 42% of control) in line with positron emission tomography data. In contrast, in PC3 and MCF-7 cells, increases in
glucose uptake (to 198% and 192% of control, respectively) and
lactate production (to 177% and 212% of control, respectively) were observed, in line with a previous hyperpolarized (13) C MRS study. This effect is probably mediated by the activation of the
phosphoinositide 3-kinase pathway and
AMP-activated protein kinase. Our findings demonstrate the value of translatable non-invasive MRS methods for the provision of information on cellular metabolism as an indication of the activation of potential feedback loops following
MEK inhibition.