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

Our findings revealed that combining aprepitant and 5-ALA synergistically regulates the proliferation and invasiveness of glioblastoma cells by altering the levels of apoptosis-related genes and intracellular PpIX levels, inhibiting cell migration, and reducing MMP-2 and MMP-9 activities. These findings suggest that the concurrent combination of aprepitant and 5-ALA may be ideal for further evaluation in the clinical setting. 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...
Source: BioFactors - Category: Biochemistry Authors: Tags: RESEARCH ARTICLE Source Type: research