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They have historically contributed to the identification of bioactive molecules and continue to play a crucial role in the discovery of new therapeutics.\n                    <jats:italic>Citrus<\/jats:italic>\n                    species, members of the\n                    <jats:italic>Rutaceae<\/jats:italic>\n                    family, represent one of the most economically important fruit tree crops worldwide, with a global yield of approximately 123\u00a0million tons in 2010. grapefruit peels were collected, dried and their active ingredients were extracted with 70% ethanol. The resulting extracts underwent phytochemical screening. The anticancer activity of the extracts was evaluated using the MTT assay, with cell viability assessed and IC\u2085\u2080 values determined. Promising fractions were further analyzed using high-performance liquid chromatography (HPLC).\n                    <jats:bold>Results<\/jats:bold>\n                    Phytochemical screening revealed high phenolic and flavonoid content, with naringenin being the most abundant compound, followed by chlorogenic acid and ferulic acid. The extract exhibited significant anticancer activity against HepG2 cells, with an IC\n                    <jats:sub>50<\/jats:sub>\n                    of 230.63\u2009\n                    <jats:italic>\u00b1<\/jats:italic>\n                    \u20091.61\u00a0\u00b5g\/ml. Molecular docking analysis of sixteen phytochemicals against the AFP protein (PDB ID: 7YIM) identified several compounds with strong binding affinities toward the predicted active site. Ellagic acid showed the highest binding affinity (-8.9\u00a0kcal\/mol), followed by rutin (-8.8\u00a0kcal\/mol), quercetin (-8.5\u00a0kcal\/mol), and naringenin (-8.4\u00a0kcal\/mol). Interaction analysis revealed multiple hydrogen bonding and \u03c0-interactions with key AFP residues, including LYS228, CYS224, PHE172, GLU489, and MET490. These findings highlight polyphenolic compounds, particularly ellagic acid and rutin, as promising lead molecules for AFP-targeted anti-hepatocellular carcinoma therapy. Grapefruit peel extract exhibits promising antioxidant and anticancer activities, demonstrating concentration-dependent cytotoxicity against HepG2 cells. Despite its lower potency compared to doxorubicin, it represents a valuable natural source of bioactive compounds. Further studies are required to elucidate its mechanisms, safety, and potential application in hepatocellular carcinoma therapy.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-56458-w","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T09:04:07Z","timestamp":1781082247000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Anticancer activity and molecular docking of active ingredients from ethanolic extract of grapefruit peels against HepG2 cell"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2900-4833","authenticated-orcid":false,"given":"Emad A.","family":"Shalaby","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3350-3451","authenticated-orcid":false,"given":"Ahmed M.","family":"Aboul-Enein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam M.","family":"Soliman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0396-0774","authenticated-orcid":false,"given":"Soha S.","family":"Mostafa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nourhan A.","family":"Aboelnaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4528-5236","authenticated-orcid":false,"given":"Clara R.","family":"Azzam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"56458_CR1","unstructured":"Asafo-Agyei, K. 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