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- Title
The SP/NK1R system promotes the proliferation of breast cancer cells through NF-κB-mediated inflammatory responses.
- Authors
Jafarinezhad, Samine; Assaran Darban, Reza; Javid, Hossein; Hashemy, Seyed Isaac
- Abstract
Background: Numerous molecules have been introduced to participate in the formation of breast cancer, the most common malignancy in women. Among them, neuropeptide substance P (SP) and its related receptor neurokinin-1 receptor (NK1R) have attracted unprecedented attention in tumorigenesis processes. In this study, we investigated the effect of the SP/NK1R pathway on the induction of oxidative stress in breast cancer and examine the therapeutic potential of NK1R inhibition in this malignancy. Methods: MCF-7 cells were treated with varying concentrations of SP and aprepitant, an FDA-approved NK1R antagonist, either as a single drug or in a combined modality. Resazurin assay was used to evaluate the anti-cancer ability of aprepitant. The alteration in the intracellular levels of reactive oxygen species (ROS) and gene expression were determined using ROS assay and the qRT-PCR analysis, respectively. Results: The stimulation of the SP/NK1R axis in the MCF-7 cells was coupled with the accumulation of ROS as well as upregulation of NF-κB and its related pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α and IL-6. In contrast, the suppression of NK1R by aprepitant halted the viability of MCF-7 cells, at least partly due to p53-mediated upregulation of p21. Moreover, aprepitant attenuated the oncogenic properties of SP by preventing the oxidative property of this neuropeptide. Conclusion: Overall, our results suggest that the SP/NK1R pathway might play a critical role in breast cancer pathogenesis, probably through inducing ROS/NF-κB-mediated inflammatory responses. Moreover, it seems that blockage of the axis has promising therapeutic value against breast cancer cells.
- Subjects
UNITED States. Food &; Drug Administration; CANCER cell proliferation; SUBSTANCE P receptors; BREAST; INFLAMMATION; TUMOR necrosis factors; SUBSTANCE P; REACTIVE oxygen species
- Publication
Cell Biochemistry & Biophysics, 2023, Vol 81, Issue 4, p787
- ISSN
1085-9195
- Publication type
Article
- DOI
10.1007/s12013-023-01171-y