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

Korfi, Faranak; Javid, Hossein; Darban, Reza Assaran; Hashemy, Seyed Isaac

doi:10.1155/2021/6620708

Cited by 27 publications

(11 citation statements)

References 53 publications

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“…In line with our results, a study has suggested that aprepitant could reduce cisplatin-induced ROS generation in PC12 of BC cells treated with aprepitant (15 µM) just 2 hours before cisplatin treatment (31). Another study that evaluated the aprepitant effect on ROS production proposed that the administration of aprepitant (35 µM) in U87 glioblastoma cells can signi cantly reduce ROS levels after 24 hours (12). In a similar investigation on U87 glioblastoma cells, ROS level remarkably was reduced as an effect of aprepitant (15 µM) treatment for 24 hours (32).…”

Section: Discussionsupporting

confidence: 90%

“…Increased levels of ROS and decreased antioxidant defense e ciency affected by SP were recorded in several studies (12); therefore, SP can modulate the cell's redox equilibrium. The de nite mechanism of NK1R and its ligand in redox equilibrium, along with antioxidant defense enzymes, has not been described adequately.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, convincing evidence has introduced the role of the tachykinin family and their receptors as an essential player in the cancer initiation and progression by modifying the cellular redox state (12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

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The effect of the Substance P/NK1R system on thioredoxin and its target gene, miR-325-3p, in MCF-7 breast cancer cells

Alaei

Soltani

Mobarra

et al. 2022

Preprint

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Purpose Breast cancer (BC) is the most frequent malignancy with a high morbidity and mortality rate among women that can be initiated and be progressed through activating the neurokinin-1 receptor (NK1R) by substance P (SP), a highly conserved member of the tachykinin peptide family. The oxidative stress-mediated role of the SP/NK1R system results in BC pathogenesis is not entirely understood. Therefore, this study was designed to shed light on the link between SP/NK1R and cellular redox state in MCF-7 breast cancer cells. Methods Aprepitant IC50 was measured by resazurin assay. Reactive oxygen species were assessed utilizing DCFDA assay. Thioredoxin (Txn) and miR-325-3p genes expression were determined through Real-Time PCR. To evaluate the Txn protein expression, western blot analysis was performed. Results We found that SP elevated ROS production in these cells. furthermore, SP leads to a remarkable down-regulation of miR-325-3p and thioredoxin (Trx) target genes and protein expression of Trx in MCF-7 cells. In addition, aprepitant inhibited SP's effects; therefore, it decreased ROS accumulation, and up-regulated Trx and miR-325-3p genes, suggesting that aprepitant may render antioxidant properties through Trx. Conclusion Oxidative stress could have an essential role in BC pathogenesis via activating the NK1R by SP. SP can decrease the BC cell's antioxidative capacity by reducing the Trx gene and protein and miR-325-3p gene. Therefore, it causes an increase in ROS production and oxidative damage. the present investigation indicates that the SP/NK1R system might be an appealing and promising therapeutic target against BC.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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The effect of the Substance P/NK1R system on thioredoxin and its target gene, miR-325-3p, in MCF-7 breast cancer cells

Alaei

Soltani

Mobarra

et al. 2022

Preprint

Self Cite

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“…Similarly, exogenous NAD + and its precursors nicotinamide mononucleotide and nicotinamide riboside attenuate ROS accumulation, restore the mitochondrial membrane potential and facilitate the healing of the CE and regeneration of corneal nerves [ 77 ]. Moreover, NK-1 repairs mitochondrial damage and clears accumulated ROS, thus improving diabetic CE wound healing and corneal sensation [ 45 , 78 , 79 ].…”

Section: Diseases Their Therapies and Akt In Cecsmentioning

confidence: 99%

The role of the PI3K/AKT signalling pathway in the corneal epithelium: recent updates

Chen

Zhang

et al. 2022

Cell Death Dis

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Phosphatidylinositol 3 kinase (PI3K)/AKT (also called protein kinase B, PKB) signalling regulates various cellular processes, such as apoptosis, cell proliferation, the cell cycle, protein synthesis, glucose metabolism, and telomere activity. Corneal epithelial cells (CECs) are the outermost cells of the cornea; they maintain good optical performance and act as a physical and immune barrier. Various growth factors, including epidermal growth factor receptor (EGFR) ligands, insulin-like growth factor 1 (IGF1), neurokinin 1 (NK-1), and insulin activate the PI3K/AKT signalling pathway by binding their receptors and promote antiapoptotic, anti-inflammatory, proliferative, and migratory functions and wound healing in the corneal epithelium (CE). Reactive oxygen species (ROS) regulate apoptosis and inflammation in CECs in a concentration-dependent manner. Extreme environments induce excess ROS accumulation, inhibit PI3K/AKT, and cause apoptosis and inflammation in CECs. However, at low or moderate levels, ROS activate PI3K/AKT signalling, inhibiting apoptosis and stimulating proliferation of healthy CECs. Diabetes-associated hyperglycaemia directly inhibit PI3K/AKT signalling by increasing ROS and endoplasmic reticulum (ER) stress levels or suppressing the expression of growth factors receptors and cause diabetic keratopathy (DK) in CECs. Similarly, hyperosmolarity and ROS accumulation suppress PI3K/AKT signalling in dry eye disease (DED). However, significant overactivation of the PI3K/AKT signalling pathway, which mediates inflammation in CECs, is observed in both infectious and noninfectious keratitis. Overall, upon activation by growth factors and NK-1, PI3K/AKT signalling promotes the proliferation, migration, and anti-apoptosis of CECs, and these processes can be regulated by ROS in a concentration-dependent manner. Moreover, PI3K/AKT signalling pathway is inhibited in CECs from individuals with DK and DED, but is overactivated by keratitis.

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“…Ghahremanloo et al also suggested that a single agent of aprepitant diminishes the viability of colon cancer-derived SW480 cells by reducing the intracellular levels of ROS and abrogating the NF- κ B signaling axis [ 37 ]. In glioblastoma, Korfi et al suggested that a higher concentration of aprepitant (35 μ M) is capable of reducing ROS production while increasing the enzymatic activity of superoxidase dismutase (SOD) and catalase [ 38 ]. Aprepitant also showed antioxidant activity in glioblastoma-derived cell lines by reducing the expression of thioredoxin reductase [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

The Therapeutic Potential of Aprepitant in Glioblastoma Cancer Cells through Redox Modification

Rezaei

Darban

Javid

et al. 2022

BioMed Research International

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Although there is no doubt regarding the involvement of oxidative stress in the development of glioblastoma, many questions remained unanswered about signaling cascades that regulate the redox status. Given the importance of the substance P (SP)/neurokinin 1 receptor (NK1R) system in different cancers, it was of particular interest to evaluate whether the stimulation of this cascade in glioblastoma-derived U87 cells is associated with the induction of oxidative stress. Our results showed that SP-mediated activation of NK1R not only increased the intracellular levels of malondialdehyde (MDA) and reactive oxygen species (ROS) but also reduced the concentration of thiol in U87 cells. We also found that upon SP addition, there was a significant reduction in the cells’ total antioxidant capacity (TAC), revealing that the SP/NK1R axis may be involved in the regulation of oxidative stress in glioblastoma cells. The significant role of SP/NK1R in triggering oxidative stress in glioblastoma has become more evident when we found that the abrogation of the axis using aprepitant reduced cell survival, probably through exerting antioxidant effects. The results showed that both MDA and ROS concentrations were significantly reduced in the presence of aprepitant, and the number of antioxidant components of the redox system increased. Overall, these findings suggest that aprepitant might exert its anticancer effect on U87 cells through shifting the balance of oxidant and antioxidant components of the redox system.

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

Cited by 27 publications

References 53 publications

The effect of the Substance P/NK1R system on thioredoxin and its target gene, miR-325-3p, in MCF-7 breast cancer cells

The effect of the Substance P/NK1R system on thioredoxin and its target gene, miR-325-3p, in MCF-7 breast cancer cells

The role of the PI3K/AKT signalling pathway in the corneal epithelium: recent updates

The Therapeutic Potential of Aprepitant in Glioblastoma Cancer Cells through Redox Modification

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