The in vitro anti‐cancer synergy of neurokinin‐1 receptor antagonist, aprepitant, and 5‐aminolevulinic acid in glioblastoma

Abstract

AbstractGlioblastoma multiforme (GBM) is the most malignant type of cerebral neoplasm in adults with a poor prognosis. Currently, combination therapy with different anti‐cancer agents is at the forefront of GBM research. Hence, this study aims to evaluate the potential anti‐cancer synergy of a clinically approved neurokinin‐1 receptor antagonist, aprepitant, and 5‐aminolevulinic acid (5‐ALA), a prodrug that elicits fluorescent porphyrins in gliomas on U‐87 human GBM cells. We found that aprepitant and 5‐ALA effectively inhibited GBM cell viability. The combinatorial treatment of these drugs exerted potent synergistic growth inhibitory effects on GBM cells. Moreover, aprepitant and 5‐ALA induced apoptosis and altered the levels of apoptotic genes (up‐regulation of Bax and P53 along with downregulation of Bcl‐2). Furthermore, aprepitant and 5‐ALA increased the accumulation of protoporphyrin IX, a highly pro‐apoptotic and fluorescent photosensitizer. Aprepitant and 5‐ALA significantly inhibited GBM cell migration and reduced matrix metalloproteinases (MMP‐2 and MMP‐9) activities. Importantly, all these effects were more prominent following aprepitant–5‐ALA combination treatment than either drug alone. Collectively, the combination of aprepitant and 5‐ALA leads to considerable synergistic anti‐proliferative, pro‐apoptotic, and anti‐migratory effects on GBM cells and provides a firm basis for further evaluation of this combination as a novel therapeutic approach for GBM.