Antitumor Effects of 5-Aminolevulinic Acid on Human Malignant Glioblastoma Cells

Abstract

5-Aminolevulinic acid (5-ALA) is a naturally occurring non-proteinogenic amino acid, which contributes to the diagnosis and therapeutic approaches of various cancers, including glioblastoma (GBM). In the present study, we aimed to investigate whether 5-ALA exerted cytotoxic effects on GBM cells. We assessed cell viability, apoptosis rate, mRNA expressions of various apoptosis-related genes, generation of reactive oxygen species (ROS), and migration ability of the human U-87 malignant GBM cell line (U87MG) treated with 5-ALA at different doses. The half-maximal inhibitory concentration of 5-ALA on U87MG cells was 500 μg/mL after 7 days; 5-ALA was not toxic for human optic cells and NIH-3T3 cells at this concentration. The application of 5-ALA led to a significant increase in apoptotic cells, enhancement of Bax and p53 expressions, reduction in Bcl-2 expression, and an increase in ROS generation. Furthermore, the application of 5-ALA increased the accumulation of U87MG cells in the SUB-G1 population, decreased the expression of cyclin D1, and reduced the migration ability of U87MG cells. Our data indicate the potential cytotoxic effects of 5-ALA on U87MG cells. Further studies are required to determine the spectrum of the antitumor activity of 5-ALA on GBM.

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

“…Thus, a better understanding of the 5‐ALA‐mediated tumor‐regulatory mechanism brings significant benefits to patients with GBM by improving the efficacy of 5‐ALA‐based therapies. In a previous study, we demonstrated the direct tumor inhibitory effects of 5‐ALA through the regulation of proliferation, apoptosis, and migration in the U‐87 human GBM cells 39 . Consistently, in this study, we observed similar pro‐apoptotic, anti‐proliferative and anti‐migratory effects of 5‐ALA in GBM cells.…”

“…In a previous study, we demonstrated the direct tumor inhibitory effects of 5-ALA through the regulation of proliferation, apoptosis, and migration in the U-87 human GBM cells. 39 Consistently, in this study, we observed similar pro-apoptotic, antiproliferative and anti-migratory effects of 5-ALA in GBM cells. In addition, 5-ALA increased the accumulation of intracellular PpIX in GBM cells, which is consistent with several other studies.…”

Inhibition of glioblastoma proliferation, invasion, and migration by Urolithin B through inducing G0/G1 arrest and targeting MMP‐2/‐9 expression and activity

“…Apoptosis and necrosis of U87 cells induced by UB (30 μM) were detected using the Annexin V-FITC staining kit as described previously. 20 A flow cytometric assessment was carried out on 10,000 stained U87 cells using a BD FACSCALIBUR™ FLOW CYTOMETER (Becton Dickinson). The program FlowJo V10 was used to examine the results.…”

Mechanisms of Cell Cycle Arrest and Apoptosis in Glioblastoma

“…5-Aminolevulinic acid (5-ALA), which induces accumulation of the protoporphyrin IX in GBM cells, is well known as the main diagnostic agent that differentiates the tumorinfiltrated tissue from adjacent healthy brain parenchyma during fluorescence-guided brain surgery [100]. Recently 5-ALA has been assigned a new role either in the context of photodynamic therapy [101] or as a direct cytotoxic agent for GBM [120]. Jalili-Nik et al report a reduction in Bcl-2 and an increase in Bax and p53 expression, and therefore an increase in apoptotic cells, in the U87MG GBM cell line after in vitro application of 5-ALA [120].…”

“…Recently 5-ALA has been assigned a new role either in the context of photodynamic therapy [101] or as a direct cytotoxic agent for GBM [120]. Jalili-Nik et al report a reduction in Bcl-2 and an increase in Bax and p53 expression, and therefore an increase in apoptotic cells, in the U87MG GBM cell line after in vitro application of 5-ALA [120].…”