Selenium Effects on Oxidative Stress-Induced Calcium Signaling Pathways in Parkinson�s Disease

Parkinson�s disease (PD) is a neurological disorder in which oxidative stress and reactive oxygen species productions are proposed to be involved in its pathogenesis. Despite considerable advancement in Selenium�s (Se) molecular biology and metabolism, we do not know much about the cell type-specific pattern of Se distribution in the brain of PD humans and experimental animals. Although, there is plenty of evidence around the role of Se deficiency in PD�s pathogenesis impacting lipid peroxidation and reducing glutathione (GSH) and glutathione peroxidase (GPX). It has been suggested that Se has an inducible role in selenium-dependent GPX activity in PD animals and humans. However, calcium as a second messenger regulates the neuron cells� essential activities, but its overloading leads to cellular oxidative stress and apoptosis. Therefore, Se�s antioxidant role can affect calcium signaling and alleviate its complications. There are signs of Se and Selenoproteins incorporation in protecting stress oxidative in various pathways. In conclusion, there is convincing proof for the crucial role of Se and Calcium in PD pathogenesis. © 2022, The Author(s), under exclusive licence to Association of Clinical Biochemists of India

The role of substance P/neurokinin 1 receptor in the pathogenesis of esophageal squamous cell carcinoma through constitutively active PI3K/Akt/NF-κB signal transduction pathways

One of the most prevalent malignancies is esophageal squamous cell carcinoma (ESCC), which is associated with high morbidity and mortality. Substance P (SP), as one of the peptides released from sensory nerves, causes the enhancement of cellular excitability through the activation of the neurokinin-1 (NK1) receptor in several human tumor cells. Aprepitant, a specific, potent, and long-acting NK1 receptor antagonist, is considered as a novel agent to inhibit proliferation and induce apoptosis in malignant cells. Since the antitumor mechanism of aprepitant in ESCC is not completely understood, we conducted this study and found that aprepitant induced growth inhibition of KYSE-30 cells and arrested cells in the G2/M phase of the cell cycle. Aprepitant also caused apoptotic cell death and inhibited activation of the PI3K/Akt axis and its downstream effectors, including NF-κB in KYSE-30 cells. Besides, quantitative real-time (qRT)-PCR analysis showed a significant down-regulation of NF-κB target genes in KYSE-30 cells, indicating a probable NF-κB-dependent mechanism involved in aprepitant cytotoxicity. Thus, the present study recommends that SP/NK1R system might, therefore, be considered as an emerging and promising therapeutic strategy against ESCC. © 2020, Springer Nature B.V

Aprepitant Promotes Caspase-Dependent Apoptotic Cell Death and G2/M Arrest through PI3K/Akt/NF- κ B Axis in Cancer Stem-Like Esophageal Squamous Cell Carcinoma Spheres

The antagonists of the neurokinin-1 receptor (NK1R) are known for their anti-inflammatory, anxiolytic, antiemetic, and anticancer activities. Aprepitant, a nonpeptide NK1R antagonist, is used in nausea and vomiting, the most common side effects of cancer chemotherapy in patients. It has been established that NK1R activation by substance P (SP), which links cancer promotion and progression to a neurokinin-mediated environment, became one mechanism that corresponds to the mitogenesis of tumor cells. Therefore, this study is aimed at explaining and evaluating the anticancer impacts of aprepitant on esophageal squamous cancer cell (ESCC) spheres by using in vitro experiments, such as resazurin, ROS, annexin-V binding, RT-PCR, and Western blot analysis. As a result, we showed that aprepitant had strong antiproliferative and cytotoxic effects on ESCC cell spheres. Also, aprepitant caused significant G2-M cell cycle arrest depending on concentration increase. Further, exposure of cells to this agent resulted in caspase -8/-9-dependent apoptotic pathway activation by modifying the expression of genes involved in apoptosis. Besides, treatment of the cells by aprepitant abrogates of the PI3K/Akt pathway, as shown by reducing the level of Akt, induces apoptotic cell death. In summary, pharmacological inhibition of NK1R with aprepitant seems to have a significant chance of treating ESCC as a single agent or in conjunction with other chemotherapeutic drugs. © 2021 Hossein Javid et al