Erlotinib and Melatonin Treatment Reduce Proliferation of the Neural Tumor Cells (SH-SY5Y) by Mediating TRPV1 Channel Function

Author : Birol Özkal - İshak Suat Övey, Ömer Çelik
Number of pages : 130-139

Abstract

Neuroblastoma, which is caused by the precursors of the sympathetic nervous system, is the most commonly encountered extracranial solid tumor in the pediatric age group. TRPV1 channels, which are a subchannel of the TRP channel family in the cell membrane, are channel permeable to calcium that are known to have increased expression based on increased free radicals. They were reported to lead to apoptosis based on increased amount of intracellular free calcium when they are excessively stimulated. With this study, we purposed to determine the effect levels of erlotinib and melatonin on neuroblastoma cells through TRPV1 channels. SH-SY5Y neuroblastoma cells were used in the study. The cell series were divided into 7 main groups as Control, Erlotinib (ERLT) (5 µM, 24 hours), MEL (1 mM, 24 hours), ERLT+CPZ, MEL+CPZ, ERLT+MEL and ERLT+MEL+CPZ. TRPV1 channel activation in all groups was achieved by capsaicin. The calcium signals, intracellular reactive oxygen types, caspase-3 and -9 and mitochondrial membrane depolarization levels were analyzed in the groups, and the groups were compared to each other. Cytosolic calcium concentration, apoptosis, mitochondrial membrane depolarization caspase-3 and caspase-9 activation, and reactive oxygen species levels were importantly higher in comparison to the control group in the ERLT (p<0.001), ERLT+MEL (p<0.001) and MEL (p<0.05; p<0.001) groups. In the comparison of the groups that used TRPV1 channel blocker (ERLT+CPZ, ERLT+MEL+CPZ, MEL+CPZ) and the groups that did not use channel blocker (ERLT, ERLT+MEL, MEL), all values were lower in the group that used the blocker (p<0.05). Using melatonin and erlotinib together in neuroblastoma tumor cells increased apoptotic pathway activity through TRPV1 channels.

Keywords

Erlotinib; Melatonin; Neuroblastoma; Oxidative Stress; TRPV1

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