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Although, 5-Fluorouracil (5-FU)-based chemotherapeutic regimens remain the mainstay for treatment of CRC, intrinsic and acquired resistance to 5-FU is the main reason for treatment failure and relapse. Adjunct or add-on therapy, therefore, should be thought of to enhance responsiveness to 5-FU. Verbascoside (VER) is a phenylethanoid glycoside ingredient present in many <jats:italic>Plantago<\/jats:italic> species and was widely used in traditional medicine. VER showed antiproliferative effects in many cancer types including CRC. In the present study, VER in <jats:italic>Plantago<\/jats:italic> seeds was identified using UPLC-MS\/MS and quantified using newly developed and validated UPLC-DAD followed by investigating its potential sensitization of CRC cells to 5-FU <jats:italic>in vitro<\/jats:italic>. The potential impact on PI3K\/AKT pathway was also investigated. A synergistic cytotoxic interaction between 5-FU and VER besides G1 cell cycle arrest were detected. Enhanced apoptosis mainly by affecting Bax and Bcl-2 and to a lesser extent Bcl-xL and p53 was also observed. Additionally, 5-FU combined to VER was capable of significantly reducing PI3K and p-AKT\/total AKT ratio. Overall, these results suggest a potential role of VER as an adjuvant treatment to decrease the resistance of CRC cells to 5-FU possibly by targeting the PI3K\/AKT pathway.<\/jats:p>","DOI":"10.1038\/s41598-018-35083-2","type":"journal-article","created":{"date-parts":[[2018,11,12]],"date-time":"2018-11-12T14:16:54Z","timestamp":1542032214000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Verbascoside: Identification, Quantification, and Potential Sensitization of Colorectal Cancer Cells to 5-FU by Targeting PI3K\/AKT Pathway"],"prefix":"10.1038","volume":"8","author":[{"given":"Yasmeen M.","family":"Attia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina M.","family":"El-Kersh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hebatallah A.","family":"Wagdy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed M.","family":"Elmazar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,11,16]]},"reference":[{"key":"35083_CR1","doi-asserted-by":"publisher","first-page":"87","DOI":"10.3322\/caac.21262","volume":"65","author":"LA Torre","year":"2015","unstructured":"Torre, L. 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