Astaxanthin Sensitizes Low SOD2-Expressing GBM Cell Lines to TRAIL Treatment via Pathway Involving Mitochondrial Membrane Depolarization

Abstract

Carotenoids have been suggested to have either anti- or pro-oxidative effects in several cancer cells, and those effects can trigger an unbalanced reactive oxygen species (ROS) production resulting in an apoptotic response. Our study aimed to evaluate the effect of the well-known carotenoid 3, 3′-dihydroxy-β, β’-carotene-4, 4-dione (astaxanthin, AXT) on glioblastoma multiforme (GBM) cells, especially as a pretreatment of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), that was previously shown to increase ROS and to induce apoptosis in cancer cells. We found that AXT by itself did not trigger apoptosis in four investigated GBM cell lines upon a 24 h treatment at various concentrations from 2.5 to 50 µM. However, in U251-MG and T98-MG GBM cells, pretreatment of 2.5 to 10 µM AXT sensitized cells to TRAIL treatment in a statistically significant manner (p p < 0.05) while less effective in U251-MG. We found that in U251-MG, superoxide dismutase (SOD) 2 expression and enzymatic activity were lower compared to CRT-MG and that overexpression of SOD2 in U251-MG abolished AXT sensitization to TRAIL treatment. Taken together, these results suggest that while AXT acts as an ROS scavenger in GBM cell lines, it also has some role in decreasing mitochondrial potential together with TRAIL in a pathway that can be inhibited by SOD2.

Keywords

• astaxanthin
• glioblastoma multiforme
• reactive oxygen species
• mitochondrial potential
• apoptosis