Abstract:
Glioblastoma multiforme is considered a highly aggressive, malignant, and lethal brain tumor. It originates from astrocytoma and is classified as grade IV, with a poor prognosis and limited effective treatments. The high nutrient demand of tumor cells led to the exploration of amino acid deprivation therapy. Enzymotherapy, a promising approach, was specifically engineered to deplete cells of amino acids like asparagine, methionine, and arginine. In our study, we utilized [HuArgI (Co) PEG5000] as targeted therapy, which was found to induce autophagy-dependent cell death. Autophagy is a cellular recycling mechanism that maintains homeostasis by breaking down damaged components. This mechanism could either protect or kill cancer cells, depending on the tumor stage and its microenvironment. Our study aimed to test the effect of arginase on autophagy and investigate the pathways involved in cancer metastasis by evaluating the migration, invasion, and adhesion of U87. Cells were treated with arginase, an autophagy inducer, and in combination with chloroquine, an autophagic flux inhibitor. Results revealed that the migration of U87 was not mediated through autophagy, and its decrease was associated with the inactivation of Rho A, a key RhoGTPase. Additionally, arginine deprivation did not significantly affect the invasion of this cell line or the expression of metalloproteinases. Therefore, further research is needed to gain a comprehensive understanding of the relationship between autophagy, Rho GTPases, and cancer metastasis.
