Role of TRPV1 Channels in Glioma Cell Viability and Survival

Abstract

High grade primary brain tumors are among the deadliest malignancies known to medicine. Anaplastic gliomas (WHO grade 3) and Glioblastoma Multiforme, or GBM, (WHO grade 4) are prevalent primary brain tumors in adults. Exploration of new avenues in treatment of GBM is absolutely crucial when taking into consideration the short (12-17 months) survival time after the diagnosis. Annually there are around 20,000 new cases, including over 4,000 pediatric (age 0-19) cases. The heat and capsaicin receptor TRPV1 is highly expressed in malignant gliomas, where the channels are thought to play a role in inducing apoptotic cell death. We evaluated TRPV1 expression in different glioma cell lines and determined the correlation of the protein expression with age and sex in the tissue samples obtained from patients with GMB. We found that age dependent correlation of TRPV1 expression is more characteristic for male patients with GBM than for females. However, in both groups TRPV1 expression was higher in patients of age 35-55 years old.We also investigated the sensitivity of different glioma cell lines to the TRPV1 agonists, including endovanilloid NADA and capsaicin. We found that 50 μM of capsaicin inhibited the cell growth and proliferation of U87 but not U251 glioma cells. The presence of TRPV1 on the plasma membrane was higher in U87 cells in comparison to U251, as confirmed by biotinylation, and may account for the effect of capsaicin on the cell viability. These results indicate that TRPV1 could play an important role in regulating Ca2+ homeostasis of primary brain tumors.