Figure 4 - Delta-Tocotrienol Modulates Glutamine Dependence by Inhibiting ASCT2 and LAT1 Transporters in Non-Small Cell Lung Cancer (NSCLC) Cells: A Metabolomic Approach
δT inhibits glutamine transporters (LAT-1 and ASCT2) and the mTOR pathway in A549 and H1299 cells. (A) The expressions of LAT-1, ASCT2, p-mTOR, mTOR, p-4EBP-1, 4EBP1, and β-actin proteins were detected by Western blot analysis in A549 and H1299 after treating with 0 µM and 30 µM concentrations of δT for 72 h. (B) The fate of glutamine uptake in A549 and H1299 involving metabolites (purple), associated key proteins (pink), and functions (orange). Glutamine in cancer facilitates exchanging of EAAs (essential amino acids) into proliferating cells via glutamine transporters (LAT1 and ASCT2), which induces mTOR activation in A549 and H1299. Activated mTOR then promotes protein translation and cell growth via activation of its downstream genes 4EBP1. The black arrows indicate pathway direction, while the red downward arrows indicate inhibition.