Alpha lipoic acid decreases hypoxia-induced apoptosis, inflammation and mitochondrial oxidative stress through inhibition of TRPA1 and TRPV1 channels in human glioma cell.

DEVECİ, Haci Ahmet; AKYUVA, Yener; NUR, Gökhan; NAZIROĞLU, Mustafa

Apoptosis, overload Ca2 entry and oxidative stress are induced by hypoxic conditions. Cancer stem cells and drug-resistant tumor cells are killed by hypoxic conditions. α-Lipoic acid (ALA) has antioxidant and oxidant properties. Recently we observed increased level of apoptosis, oxidative stress and TRPV1 activation in breast cancer cells by the ALA treatment. The aim of this study was to evaluate if a combination therapy of ALA with hypoxia can alter the effect of this hypoxia in the human glioblastoma (DBTRG) cells. The DBTRG cells were divided into four treatment groups as control, ALA (50 mM), and hypoxia and hypoxia ALA. Hypoxia in the cells was induced by CoCl2 (200 mM). Apoptosis, mitochondrial membrane depolarization (JC1), reactive oxygen species (ROS) production, IL-1b, IL-18, caspase 3 and 9 levels are increased through activating TRPA1 and TRPV1 in the cells by the hypoxia induction, although cell viability, reduced glutathione (GSH) and glutathione peroxidase (GSH-Px) values were decreased by the treatments. However, the cell viability, GSH and GSH-Px values were decreased in the cells by TRPA1 (AP18) and TRPV1 (capsazepine) blockers, and ALA treatments, although ROS, JC1, apoptosis, IL-18, caspase 3 and 9 levels were decreased by the ALA treatment. In conclusion, apoptosis, inflammatory and oxidant effects of hypoxia were increased by activation of TRPA1 and TRPV1 channels, 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 and inflammation.

OXIDATIVE stress; APOPTOSIS; LIPOIC acid; OXIDATION-reduction reaction; ANTIOXIDANTS

Journal of Cellular Neuroscience & Oxidative Stress, 2018, Vol 10, Issue 2, p737

2149-7222

Academic Journal