{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:24:43Z","timestamp":1792113883268,"version":"4.4.0"},"reference-count":41,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,8,27]],"date-time":"2022-08-27T00:00:00Z","timestamp":1661558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Date palm fruit seed (Phoenix dactylifera L.) extract (DSE), an under-utilized resource, is a rich source of polyphenols with high potency for disease prevention and antioxidative activities. For the first time, the present study demonstrated that DSE inhibits labile iron activity and DNA and BSA damage and inhibits acetylcholinesterase and tyrosinase activities. Moreover, DSE reduces the proliferation of hepatic, colorectal, and breast cancer cells dose-dependently through apoptotic mechanisms. Furthermore, DSE significantly suppressed the expression of both BCl-2 and P21 genes and increased the P53 expression level when compared with the untreated cells and the 5-FU treated cells. These findings suggest a strong potential for DSE in protecting against the iron-catalyzed ferroptosis that results in programmed cell death. The results also confirm the efficacy of DSE against cancer cells. Therefore, DSE constitutes a valuable candidate for developing functional foods and for natural compound-based chemotherapy for the pharmaceutical and nutraceutical industries.<\/jats:p>","DOI":"10.3390\/nu14173536","type":"journal-article","created":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T22:53:42Z","timestamp":1661813622000},"page":"3536","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Polyphenol-Rich Date Palm Fruit Seed (Phoenix Dactylifera L.) Extract Inhibits Labile Iron, Enzyme, and Cancer Cell Activities, and DNA and Protein Damage"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7768-8788","authenticated-orcid":false,"given":"Hosam M.","family":"Habib","sequence":"first","affiliation":[{"name":"Functional Foods and Nutraceuticals Laboratory (FFNL), Dairy Science and Technology Department, Faculty of Agriculture, Alexandria University, Alexandria P.O. Box 21545, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0724-8477","authenticated-orcid":false,"given":"Esmail M.","family":"El-Fakharany","sequence":"additional","affiliation":[{"name":"Protein Research Department, Genetic Engineering and Biotechnology Research Institute GEBRI, City for Scientific Research and Technology Applications, New Borg EL Arab, Alexandria P.O. Box 21934, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Usama D.","family":"Souka","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma M.","family":"Elsebaee","sequence":"additional","affiliation":[{"name":"Department of Home Economics, Faculty of Specific Education, Fayoum University, Fayoum P.O. Box 63514, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed G.","family":"El-Ziney","sequence":"additional","affiliation":[{"name":"Functional Foods and Nutraceuticals Laboratory (FFNL), Dairy Science and Technology Department, Faculty of Agriculture, Alexandria University, Alexandria P.O. Box 21545, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wissam H.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,27]]},"reference":[{"key":"ref_1","unstructured":"(2022, March 01). Food and Agriculture Organization of the United Nations. Available online: http:\/\/faostat.fao.org\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1080\/09637480802314639","article-title":"Nutritional Quality Evaluation of Eighteen Date Pit Varieties","volume":"60","author":"Habib","year":"2009","journal-title":"Int. J. Food Sci. Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.13005\/bpj\/2204","article-title":"Effect of Chronic Administration of Date Palm Seeds Extract on Some Biochemical Parameters, Oxidative Status and Caspase-3 Expression in Female Albino Rats","volume":"14","author":"Mahmoud","year":"2021","journal-title":"Biomed. Pharmacol. J."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Devaraj, A., and Mahalingam, G. (2021). Bioactive Molecules from Medicinal Plants as Functional Foods (Biscuits) for the Benefit of Human Health as Antidiabetic Potential. Bioactive Compounds in Nutraceutical and Functional Food for Good Human Health, IntechOpen.","DOI":"10.5772\/intechopen.93352"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1080\/00986445.2019.1650034","article-title":"Extraction, Characterization and Optimization of High Quality Bio-Oil Derived from Waste Date Seeds","volume":"208","author":"Kareem","year":"2021","journal-title":"Chem. Eng. Commun."},{"key":"ref_6","first-page":"1","article-title":"Physicochemical, Rheological, and Sensory Properties of Gluten-Free Cookie Produced by Flour of Chestnut, Date Seed, and Modified Starch","volume":"2022","author":"Mohammadi","year":"2022","journal-title":"J. Food Qual."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"87","DOI":"10.9734\/jeai\/2021\/v43i1130760","article-title":"Development and Quality Evaluation of Date Seed Powder Incorporated Cookies","volume":"43","author":"Sriharsha","year":"2021","journal-title":"J. Exp. Agric. Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.sajb.2020.10.015","article-title":"Phenolic Profile, Antioxidant Activity and Enzyme Inhibitory Capacities of Fruit and Seed Extracts from Different Algerian Cultivars of Date (Phoenix dactylifera L.) Were Affected by in Vitro Simulated Gastrointestinal Digestion","volume":"137","author":"Djaoudene","year":"2021","journal-title":"S. Afr. J. Bot."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Platat, C., Hilary, S., Tomas-Barberan, F., Martinez-Blazquez, J., Al-Meqbali, F., Souka, U., Al-Hammadi, S., and Ibrahim, W. (2019). Urine Metabolites and Antioxidant Effect after Oral Intake of Date (Phoenix dactylifera L.) Seeds-Based Products (Powder, Bread and Extract) by Human. Nutrients, 11.","DOI":"10.3390\/nu11102489"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1002\/jsfa.6387","article-title":"Polyphenolic Compounds in Date Fruit Seed (Phoenix dactylifera): Characterisation and Quantification by Using UPLC-DAD-ESI-MS","volume":"94","author":"Habib","year":"2014","journal-title":"J. Sci. Food Agric."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"125969","DOI":"10.1016\/j.foodchem.2019.125969","article-title":"Polyphenol Characterisation of Phoenix dactylifera L. (Date) Seeds Using HPLC-Mass Spectrometry and Its Bioaccessibility Using Simulated in-Vitro Digestion\/Caco-2 Culture Model","volume":"311","author":"Hilary","year":"2020","journal-title":"Food Chem."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Mitra, S., Tareq, A.M., Das, R., Emran, T.B., Nainu, F., Chakraborty, A.J., Ahmad, I., Tallei, T.E., Idris, A.M., and Simal-Gandara, J. (2022). Polyphenols: A First Evidence in the Synergism and Bioactivities. Food Rev. Int., 1\u201323.","DOI":"10.1080\/87559129.2022.2026376"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1039\/C6FO01164K","article-title":"DNA and BSA Damage Inhibitory Activities, and Anti-Acetylcholinesterase, Anti-Porcine \u03b1-Amylase and Antioxidant Properties of Dolichos Lablab Beans","volume":"8","author":"Habib","year":"2017","journal-title":"Food Funct."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"12393","DOI":"10.1038\/s41598-022-16608-2","article-title":"Grape Seed Proanthocyanidin Extract Inhibits DNA and Protein Damage and Labile Iron, Enzyme, and Cancer Cell Activities","volume":"12","author":"Habib","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.foodchem.2013.12.044","article-title":"Bioactive Components, Antioxidant and DNA Damage Inhibitory Activities of Honeys from Arid Regions","volume":"153","author":"Habib","year":"2014","journal-title":"Food Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.freeradbiomed.2013.06.026","article-title":"Mitochondrial Superoxide Mediates Labile Iron Level: Evidence from Mn-SOD-Transgenic Mice and Heterozygous Knockout Mice and Isolated Rat Liver Mitochondria","volume":"65","author":"Ibrahim","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"130415","DOI":"10.1016\/j.foodchem.2021.130415","article-title":"Inhibitory Effects of Honey from Arid Land on Some Enzymes and Protein Damage","volume":"364","author":"Habib","year":"2021","journal-title":"Food Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1039\/C6FO01162D","article-title":"Functional, Bioactive, Biochemical, and Physicochemical Properties of the Dolichos Lablab Bean","volume":"8","author":"Habib","year":"2017","journal-title":"Food Funct."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"16769","DOI":"10.1038\/s41598-017-16962-6","article-title":"Efficiency of Novel Nanocombinations of Bovine Milk Proteins (Lactoperoxidase and Lactoferrin) for Combating Different Human Cancer Cell Lines","volume":"7","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s10930-018-9770-1","article-title":"The Use of Human, Bovine, and Camel Milk Albumins in Anticancer Complexes with Oleic Acid","volume":"37","author":"Litus","year":"2018","journal-title":"Protein J."},{"key":"ref_21","first-page":"350","article-title":"Phytochemical Compositions and Antioxidant Capacity of Three Date (Phoenix dactylifera L.) Seeds Varieties Grown in the South East Morocco","volume":"16","author":"Bouhlali","year":"2017","journal-title":"J. Saudi Soc. Agric. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.apjtb.2015.11.008","article-title":"In Vitro Inhibitory Effects on \u03b1-Glucosidase and \u03b1-Amylase Level and Antioxidant Potential of Seeds of Phoenix dactylifera L.","volume":"6","author":"Khan","year":"2016","journal-title":"Asian Pac. J. Trop. Biomed."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4953","DOI":"10.1039\/C9FO01125K","article-title":"Phoenix dactylifera L. Seeds: A by-Product as a Source of Bioactive Compounds with Antioxidant and Enzyme Inhibitory Properties","volume":"10","author":"Djaoudene","year":"2019","journal-title":"Food Funct."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.foodchem.2018.09.040","article-title":"In Vitro Antioxidant Activity of Kyoho Grape Extracts in DPPH and ABTS Assays: Estimation Methods for EC50 Using Advanced Statistical Programs","volume":"275","author":"Sridhar","year":"2019","journal-title":"Food Chem."},{"key":"ref_25","first-page":"100217","article-title":"Proximate Composition of Polyphenolic, Phytochemical, Antioxidant Activity Content and Lipid Profiles of Date Palm Seeds Oils (Phoenix dactylifera L.)","volume":"6","author":"Ourradi","year":"2021","journal-title":"J. Agric. Food Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e03436","DOI":"10.1016\/j.heliyon.2020.e03436","article-title":"Phenolic Profile and Anti-Inflammatory Activity of Four Moroccan Date (Phoenix dactylifera L.) Seed Varieties","volume":"6","author":"Bouhlali","year":"2020","journal-title":"Heliyon"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"111228","DOI":"10.1016\/j.biopha.2021.111228","article-title":"The Role of Iron in the Pathogenesis of COVID-19 and Possible Treatment with Lactoferrin and Other Iron Chelators","volume":"136","author":"Habib","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"124910","DOI":"10.1016\/j.foodchem.2019.05.184","article-title":"Five Individual Polyphenols as Tyrosinase Inhibitors: Inhibitory Activity, Synergistic Effect, Action Mechanism, and Molecular Docking","volume":"297","author":"Yu","year":"2019","journal-title":"Food Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"129369","DOI":"10.1016\/j.foodchem.2021.129369","article-title":"Understanding the Combined Effect and Inhibition Mechanism of 4-Hydroxycinnamic Acid and Ferulic Acid as Tyrosinase Inhibitors","volume":"352","author":"Yu","year":"2021","journal-title":"Food Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"103587","DOI":"10.1016\/j.jff.2019.103587","article-title":"Inhibition of Porcine Pancreatic \u03b1-Amylase Activity by Chlorogenic Acid","volume":"64","author":"Zheng","year":"2020","journal-title":"J. Funct. Foods"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4290702","DOI":"10.1155\/2020\/4290702","article-title":"Inhibition of Digestive Enzyme and Stimulation of Human Liver Cells (HepG2) Glucose Uptake by Date Seeds Extract","volume":"2020","author":"Shakoor","year":"2020","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Hinkaew, J., Aursalung, A., Sahasakul, Y., Tangsuphoom, N., and Suttisansanee, U. (2021). A Comparison of the Nutritional and Biochemical Quality of Date Palm Fruits Obtained Using Different Planting Techniques. Molecules, 26.","DOI":"10.3390\/molecules26082245"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"494","DOI":"10.4103\/pm.pm_623_18","article-title":"Anticancer Potential of Seed Extract and Pure Compound from Phoenix dactylifera on Human Cancer Cell Lines","volume":"15","year":"2019","journal-title":"Pharmacogn. Mag."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"00017","DOI":"10.15406\/mojt.2015.01.00017","article-title":"Date Seed Extract Diminished Apoptosis Event in Human Colorectal Carcinoma Cell Line","volume":"1","author":"Rezaei","year":"2015","journal-title":"MOJ Toxicol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"571","DOI":"10.3389\/fnut.2021.667514","article-title":"In-Vitro Investigation of Polyphenol-Rich Date (Phoenix dactylifera L.) Seed Extract Bioactivity","volume":"8","author":"Hilary","year":"2021","journal-title":"Front. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"32","DOI":"10.3126\/ijasbt.v9i1.36110","article-title":"Bangladeshi Wild Date Palm Fruits (Phoenix sylvestris): Promising Source of Anti-Cancer Agents for Hepatocellular Carcinoma Treatment","volume":"9","author":"Lamia","year":"2021","journal-title":"Int. J. Appl. Sci. Biotechnol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"829.20","DOI":"10.1096\/fasebj.28.1_supplement.829.20","article-title":"Date Seed (Phoenix dactylifera) Extract Reduces the Proliferation of Pancreatic Cancer Cells, DNA Damage and Superoxide-dependent Iron Release from Ferritin in Vitro (829.20)","volume":"28","author":"Habib","year":"2014","journal-title":"FASEB J."},{"key":"ref_38","first-page":"358","article-title":"The Anti-Proliferative Activity of Phoenix dactylifera Seed Extract on MCF-7 Breast Cancer Cell Line","volume":"41","author":"Sahib","year":"2016","journal-title":"Int. J. Pharm. Sci. Rev. Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Khan, M.A., Singh, R., Siddiqui, S., Ahmad, I., Ahmad, R., Upadhyay, S., Barkat, M.A., Ali, A.M.A., Zia, Q., and Srivastava, A. (2022). Anticancer Potential of Phoenix dactylifera L. Seed Extract in Human Cancer Cells and pro-Apoptotic Effects Mediated through Caspase-3 Dependent Pathway in Human Breast Cancer MDA-MB-231 Cells: An in Vitro and in Silico Investigation. BMC Complement Altern. Med., 22.","DOI":"10.1186\/s12906-022-03533-0"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1186\/s12935-021-02396-8","article-title":"P53 Signaling in Cancer Progression and Therapy","volume":"21","author":"Marei","year":"2021","journal-title":"Cancer Cell Int."},{"key":"ref_41","first-page":"1","article-title":"Post-Translational Modifications of P53 in Ferroptosis: Novel Pharmacological Targets for Cancer Therapy","volume":"13","author":"Zhang","year":"2022","journal-title":"Front. Pharmacol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/17\/3536\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:16:30Z","timestamp":1760141790000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/17\/3536"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,27]]},"references-count":41,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["nu14173536"],"URL":"https:\/\/doi.org\/10.3390\/nu14173536","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,27]]}}}