Selenium enhances TRPA1 channel-mediated activity of temozolomide in SH-SY5Y neuroblastoma cells.

Purpose: Neuroblastoma is a malignant solid tumor that originates from the sympathetic nervous system in early childhood. Temozolomide is used for treatment in high-risk groups with low treatment response of neuroblastomas. TRPA1 channels in neuroblastoma cells are calcium permeable channels that can be activated by reactive oxygen species (ROT). In this study, we aimed to evaluate the level of activity of temozolomide and selenium in neuroblastoma cells via TRPA1 channels.

Method: Seven main groups were formed using SH-SY5Y neuroblastoma cells. The control was divided into temozolomide (TMZ) (100 μM, 24 h), TMZ+SEL+AP18, SEL (sodium selenite, 100 μM, 24 h), and SEL+AP18 groups. Intergroup calcium signaling, intracellular reactive oxygen species, caspase-3 and caspase-9, and mitochondrial depolarization analyses were performed by channel activation with TRPA1 agonist cinnamaldehyde in all groups.

Results: Cytosolic calcium concentration, apoptosis, caspase-3 and caspase-9 activation, mitochondrial membrane depolarization, and ROT levels were higher in TMZ (p < 0.001), TMZ+SEL (p < 0.001), and SEL (p < 0.05) groups than the control group. TRPA1 was lower in TTMZ+AP18, TMZ+SEL+AP18, and SEL+AP18 groups with channel blockers than respectively TMZ, TMZ+SEL, and SEL groups without channel blockers (p < 0.05).

Conclusion: The use of selenium with temozolomide increased the apoptotic efficacy of temozolomide via TRPA1 channels on tumor cells.