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.
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Author contributions
RAD and SIH contributed to the study conception and design. Material preparation, data collection and analysis were performed by SJ and HJ. The first draft of the manuscript was written by SJ and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Jafarinezhad, S., Assaran Darban, R., Javid, H. et al. The SP/NK1R system promotes the proliferation of breast cancer cells through NF-κB-mediated inflammatory responses. Cell Biochem Biophys 81, 787–794 (2023). https://doi.org/10.1007/s12013-023-01171-y
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DOI: https://doi.org/10.1007/s12013-023-01171-y