A Novel Mechanism of Endoplasmic Reticulum Stress‐ and c‐Myc‐Degradation‐Mediated Therapeutic Benefits of Antineurokinin‐1 Receptor Drugs in Colorectal Cancer
| العنوان: | A Novel Mechanism of Endoplasmic Reticulum Stress‐ and c‐Myc‐Degradation‐Mediated Therapeutic Benefits of Antineurokinin‐1 Receptor Drugs in Colorectal Cancer |
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| المؤلفون: | Xurui Cheng, Jun-Jie Ma, Yueming Meng, Yong Wang, Yue Shi, Zhi-Bin Yan, Jian Kang, Caiyun Fu, Xiang-Yu Hong, Xi Wang, Gang Shao, Lingfei Wang, Yihai Cao, Qiyu Zhang |
| المصدر: | Advanced Science Advanced Science, Vol 8, Iss 21, Pp n/a-n/a (2021) |
| بيانات النشر: | John Wiley and Sons Inc., 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | MAPK/ERK pathway, chemotherapy resistance, Quinuclidines, Science, General Chemical Engineering, Transplantation, Heterologous, General Physics and Astronomy, Medicine (miscellaneous), Mice, Nude, Antineoplastic Agents, Apoptosis, CHOP, MAPK signal pathway, medicine.disease_cause, Biochemistry, Genetics and Molecular Biology (miscellaneous), Proto-Oncogene Proteins c-myc, Mice, Neurokinin-1 Receptor Antagonists, Piperidines, Cell Line, Tumor, human colorectal cancer, medicine, Animals, Humans, General Materials Science, Protein kinase A, Extracellular Signal-Regulated MAP Kinases, Research Articles, neurokinin‐1 receptor, Kinase, Endoplasmic reticulum, General Engineering, Cancer, medicine.disease, Endoplasmic Reticulum Stress, Survival Rate, Drug Resistance, Neoplasm, Cancer research, Unfolded protein response, Carcinogenesis, ER stress, Colorectal Neoplasms, Aprepitant, Research Article, Signal Transduction |
| الوصف: | The neurokinin‐1 receptor (NK‐1R) antagonists are approved as treatment for chemotherapy‐associated nausea and vomiting in cancer patients. The emerging role of the substance P‐NK‐1R system in oncogenesis raises the possibility of repurposing well‐tolerated NK‐1R antagonists for cancer treatment. This study reports that human colorectal cancer (CRC) patients with high NK‐1R expression have poor survival, and NK‐1R antagonists SR140333 and aprepitant induce apoptotic cell death in CRC cells and inhibit CRC xenograft growth. This cytotoxicity induced by treatment with NK‐1R antagonists is mediated by induction of endoplasmic reticulum (ER) stress. ER stress triggers calcium release, resulting in the suppression of prosurvival extracellular signal‐regulated kinase (ERK)‐c‐Myc signaling. Along with ER calcium release, one ER stress pathway mediated by protein kinase RNA‐like ER kinase (PERK) is specifically activated, leading to increased expression of proapoptotic C/EBP‐homologous protein (CHOP). Moreover, NK‐1R antagonists enhance the efficacy of chemotherapy by increasing the sensitivity and overcoming resistance to 5‐fluorouracil in CRC cells through the induction of sustained ER stress and the consequent suppression of ERK‐c‐Myc signaling both in vitro and in vivo. Collectively, the findings provide novel mechanistic insights into the efficacy of NK‐1R antagonists either as a single agent or in combination with chemotherapy for cancer treatment. The neurokinin‐1 receptor antagonists are repurposed as a new treatment option for patients with colorectal cancer via activation of endoplasmic reticulum stress to induce apoptosis. |
| اللغة: | English |
| تدمد: | 2198-3844 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3c36da37d48676f8313e18453cecfc2b http://europepmc.org/articles/PMC8564433 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....3c36da37d48676f8313e18453cecfc2b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 21983844 |
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