Fig. 8

Schematic model for regulation of stem-like side population cells by glutamine. Glutamine is a precursor for glutamine synthesis and is important in maintaining redox balance. Depletion of glutamine would result in a decrease in GSH, and subsequently causes an accumulation of ROS, which in turn induces phosphorylation of β-catenin and thus inactivate this pathway, lead to loss of stemness. Targeting glutamine metabolism either by enzymatic elimination of glutamine in the tumor microenvironment using L-ASP or by inhibition of intracellular conversion of glutamine to glutamate using glutaminase (GLS) inhibitors such as BPTES and compound 968 may decrease cancer stem cells through increasing ROS and attenuation of the beta-catenin activity