Alpha lipoic acid attenuates hypoxia-induced apoptosis, inflammation and mitochondrial oxidative stress via inhibition of TRPA1 channel in human glioblastoma cell line

Apoptosis, overload Ca²⁺ entry and oxidative stress are induced in neurons by hypoxia. Drug-resistant cancer cells are killed by hypoxic conditions. α-Lipoic acid (ALA) has antioxidant and pro-oxidant functions. The TRPA1 channel is activated by oxidative stress and pro-oxidant ALA may have a regulator role in the TRPA1 activity in the human glioblastoma (DBTRG) cells. The aim of this study was to evaluate if a combination therapy of ALA with a hypoxia can alter the effect of this hypoxia through TRPA1 activation in the DBTRG cells. The DBTRG cells were divided into four treatment groups as control, ALA (50 μM), and hypoxia and hypoxia + ALA. Hypoxia in the cells was induced by CoCl₂ (200 μM). Apoptosis, Annexin V, mitochondrial membrane depolarization (JC-1), reactive oxygen species (ROS) production, IL-1β, IL-18, caspase 3 and 9 values were increased through activation of TRPA1 (cinnamaldehyde) in the cells by the hypoxia induction, although cell viability, reduced glutathione and glutathione peroxidase values were decreased by the treatments. The values were modulated in the cells by TRPA1 blocker (AP18) and ALA treatments. Involvements of TRPA1 activity on values in the cells were also confirmed by patch-clamp and laser confocal microscopy analyses. In conclusion, apoptotic, inflammatory and oxidant effects of hypoxia were increased by activation of TRPA1, but its action on the values was decreased by the ALA treatment. ALA treatment could be used as an effective strategy in the treatment of hypoxia-induced oxidative stress, apoptosis and inflammation in the neurons.