The Emerging Role of Neurokinin-1 Receptor Blockade Using Aprepitant in the Redox System of Esophageal Squamous Cell Carcinoma

Objectives Oxidative stress contributes to many diseases' pathogenesis, including esophageal squamous cell carcinoma (ESCC). Substance P (SP), a member of the tachykinins family, has a crucial role in regulating cellular oxidative stress by interacting with its specific receptor, called neurokinin-1 receptor (NK1R). On the other hand, the blockade of NK1R through Aprepitant has been shown as an antioxidant factor in various clinical diseases. Since SP/NK1R and Aprepitant's exact impact on the redox system in ESCC cells is not fully clarified, we aimed to study these research gaps. Methods The resazurin assay was conducted to detect the aprepitant's impact on the viability of two ESCC cell lines (YM1 and KYSE-30). Next, the levels of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) as an index of oxidative stress were measured after treating the cells by SP and Aprepitant. Also, we studied superoxide dismutase, catalase, thioredoxin system (thioredoxin and thioredoxin reductase), glutaredoxin activities, the level of the thiol group, and total antioxidant capacity to assess the effect of the SP/NK1R system on the antioxidant property of ESCC cell lines. Results SP enhanced intracellular ROS and MDA levels in ESCC, whereas aprepitant significantly decreased these markers. Moreover, aprepitant showed an excellent antioxidant effect in ESCC cell lines by restoring SP-inhibited antioxidant markers' activities. Conclusions The induction of NK1R by SP has a vital role in developing ESCC by promoting oxidative stress, which aprepitant can inhibit. Towards this end, it is suggested that targeting NK1R with Aprepitant may modulate oxidation in patients with ESCC.