Downregulation of TRPM8 channels induce cell death in human DBTRG glioblastoma cells

Abstract

The calcium ion (Ca²⁺) is among the most important second messengers for cellular metabolic processes. Cytosolic calcium concentration ([Ca²⁺]c) is regulated by calcium signals and that are driven by different kinds of cation channels including the Transient Receptor Potential (TRP) channels. The TRPM8 cation channels are calcium ion (Ca²⁺) permeable non-selective cation channels belongs TRP superfamily. The TRPM8 is expressed in central and peripheral nervous system components especially in pain and cold sensation related nerve endings. Glioblastoma is the most potent cancer type of the human brain, and patients has less survival time after the detection of disease. Recently, TRPM8 cation channels involved in several types of cancers including glioblastoma because of high expression levels in cancer tissues. Hence, [Ca²⁺]c may change depend on TRPM8 activations from extracellular liquid to cytosol and it can be targeted for prevention of cancer progression. Therefore, we have investigated effects of downregulation of TRPM8 cation channels by siRNA transfections and pharmacological blockade of the channels with its specific antagonist on apoptosis and cell viability, intracellular reactive oxygen species production (iROS), mitochondrial membrane depolarization levels (MMD), caspase 3 and caspase 9 enzyme activity values in DBTRG glioblastoma cells. We have found that TRPM8 cation channels has crucial role in cancer progression and uncontrolled cell proliferation, however TRPM8 cation channels’ pharmacologically blockade, or prevention of the channel expression may induce cell death and cellular apoptotic processes. In conclusion, TRPM8 cation channel blockers or downregulation of the channels by genetic manipulations can be useful and potential therapeutic approach against to glioblastoma progression.