{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:23:57Z","timestamp":1789658637402,"version":"4.0.1"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T00:00:00Z","timestamp":1639008000000},"content-version":"vor","delay-in-days":342,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004748","name":"Mashhad University of Medical Sciences","doi-asserted-by":"publisher","award":["961738"],"award-info":[{"award-number":["961738"]}],"id":[{"id":"10.13039\/501100004748","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>The antagonists of the neurokinin\u20101 receptor (NK1R) are known for their anti\u2010inflammatory, 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\u2010mediated 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\u2010V binding, RT\u2010PCR, 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\u2010M cell cycle arrest depending on concentration increase. Further, exposure of cells to this agent resulted in caspase \u20108\/\u20109\u2010dependent 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.<\/jats:p>","DOI":"10.1155\/2021\/8808214","type":"journal-article","created":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T21:50:05Z","timestamp":1639086605000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Aprepitant Promotes Caspase\u2010Dependent Apoptotic Cell Death and G2\/M Arrest through PI3K\/Akt\/NF\u2010<i>\u03ba<\/i>B Axis in Cancer Stem\u2010Like Esophageal Squamous Cell Carcinoma Spheres"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2248-7708","authenticated-orcid":false,"given":"Hossein","family":"Javid","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9989-9818","authenticated-orcid":false,"given":"Amir R.","family":"Afshari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8915-3596","authenticated-orcid":false,"given":"Farnaz","family":"Zahedi Avval","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7068-2970","authenticated-orcid":false,"given":"Jahanbakhsh","family":"Asadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1323-5250","authenticated-orcid":false,"given":"Seyed Isaac","family":"Hashemy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12,9]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.21873\/anticanres.13259"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-020-1375-4"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.12726"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms15058169"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.28918"},{"key":"e_1_2_10_6_2","article-title":"Esophageal cancer stem cells and implications for future therapeutics","volume":"9","author":"Qian X.","year":"2016","journal-title":"OncoTargets and Therapy"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.32285"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109594"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13105-019-00697-1"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1101\/2021.05.16.444192"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2013.07.024"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-019-04599-9"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-018-4387-1"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-020-05432-4"},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.12.024"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.2174\/157018006777574168"},{"key":"e_1_2_10_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-020-05330-9"},{"key":"e_1_2_10_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2009.06032.x"},{"key":"e_1_2_10_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-010-9594-0"},{"key":"e_1_2_10_20_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.2000.01606.x"},{"key":"e_1_2_10_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12038-015-9530-8"},{"key":"e_1_2_10_22_2","article-title":"Auraptene-induced cytotoxicity mechanisms in human malignant glioblastoma (U87) cells: role of reactive oxygen species (ROS)","volume":"18","author":"Afshari A. 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