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Egypt, as a developing country, has a high-rise incidence of cancer. The current study objective was to investigate the antitumor influences of ellagitannin-loaded CS-PEG-decorated PLGA nano-prototypes against human colorectal cancer cell lines (HCT 116 as well as Caco-2) in vitro. Doxorubicin (DOX), punicalin (PN), and punicalagin (PNG)-encapsulated chitosan-polyethylene glycol-decorated PLGA (PLGA-CS-PEG) nanoparticles (NPs) were described. The cytotoxicity of each preparation was evaluated using MTT assays in HCT 116 as well as Caco-2 cells during G0, G1, S, and G2 cell cycle phases. Cell cycle-related gene expression and protein levels were measured after treatment. Reactive oxygen species (ROS) levels were also measured. Both PN and PNG PLGA-CS-PEG NPs induce colon cancer cell death with cell cycle arrest in the G1 phase in vitro. Caco-2 cells were more sensitive to the nano-therapy than HCT 116 cells. Upon treatment, the ratio of Bax to Bcl-2 expression was increased following nano-therapy, with increased levels of Cas-3 and decreased expression of Bcl-2, PI3k, and NF-\u0138B compared to control. The nitric oxide level (NO), a marker of ROS, was increased following nano-therapy compared to control. In conclusion, ROS-mediated cell cycle arrest can be induced by PN as well as PNG nano-therapy in cell lines of colorectal cancer.<\/jats:p>","DOI":"10.1007\/s12013-023-01132-5","type":"journal-article","created":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T14:02:31Z","timestamp":1681740151000},"page":"313-323","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["An ellagitannin-loaded CS-PEG decorated PLGA nano-prototype promotes cell cycle arrest in colorectal cancer cells"],"prefix":"10.1007","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9875-7591","authenticated-orcid":false,"given":"Ahmed A.","family":"Abd-Rabou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9021-1922","authenticated-orcid":false,"given":"Aziza B.","family":"Shalby","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6414-4981","authenticated-orcid":false,"given":"Soheir E.","family":"Kotob","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,4,17]]},"reference":[{"key":"1132_CR1","unstructured":"WHO. 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