The Effect of SP/NK1R on the Expression and Activity of Catalase and Superoxide Dismutase in Glioblastoma Cancer Cells.

Faranak Korfi,Reza Assaran Darban,Seyed Isaac Hashemy,Hossein Javid,Zubeyir Huyut

doi:10.1155/2021/6620708

Abstract

Introduction Glioblastoma is the most malignant brain tumor with different therapeutic protocols, including surgery, radiotherapy, and chemotherapy. Substance P (SP), a peptide released by sensory nerves, increases cellular excitability by activating the neurokinin-1 receptor (NK1R) in several human tumor cells. Aprepitant is a potent and long-lasting NK1R antagonist, considered a new agent for inhibiting proliferation and induction of apoptosis in malignant cells. This study aimed to evaluate the effects of the SP/NK1R system on the expression and activity of catalase and superoxide dismutase (SOD) in the glioblastoma U87 cancer cell line. Methods Cytotoxicity was measured by the resazurin test, 24 hours after treatment, with increasing aprepitant concentrations. The production of reactive oxygen species (ROS) was also measured 24 hours after treatment with SP and aprepitant. Enzymes activity of catalase and SOD was measured using the corresponding assay kits. Real-time PCR also measured their expression. Results Aprepitant significantly reduced the viability of U87 cells in a concentration-dependent manner. ROS production was significantly reduced, and the activity of catalase and SOD increased after treatment with aprepitant. The expression of catalase and SOD enzymes also increased significantly in the presence of aprepitant. Conclusion The present study showed that aprepitant inhibited SP's oxidizing effects via inducing the antioxidant effects of catalase and SOD in the U87 cell line. Therefore, this drug might be introduced as a potential candidate for controlling glioblastoma cancer in animal models and clinical trials.

Highlights

Glioblastoma is the most malignant brain tumor with different therapeutic protocols, including surgery, radiotherapy, and chemotherapy
We investigated the Substance P (SP)/neurokinin-1 receptor (NK1R) system’s effect on the expression and activity of catalase and superoxide dismutase in glioblastoma cancer. e results showed that substance P induced the production of reactive oxygen species (ROS) by binding to the NK1 receptor in these cells
It is known that the tachykinin (TK) system, which plays a crucial role in the transmission of neural messages in the central and peripheral nervous systems, may be involved in the progression of cancers. e biological activities of SP, the most basic member of the mammalian TK peptides, are mediated through a G-protein coupled receptor (GPCR) named neurokinin-1 receptor, and it is known that the SP/NK1R system is involved in survival, proliferation, progression, and metastasis of several human tumor cells [21, 53]

Summary

Introduction

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor worldwide, and its occurrence is increasing [1, 2] It is the third leading cause of death from cancer and overall in individuals aged 15–39 years [3]. Several studies have recently demonstrated that SP induces a series of signaling pathways through NK1R that mediate cellular excitability in several human tumor cells. It has important roles in forming and spreading various tumor cells via migration, angiogenesis, and metastasis [11,12,13,14,15,16]. This study aimed to explore the possible effect of the SP/NK1R system and aprepitant, a potent NK1R antagonist, on the expression and activity of catalase and superoxide dismutase enzymes, two of the most well-known antioxidant enzymes, in U87 glioblastoma cancer cells

Materials and Methods

Discussion

Findings

Conclusion