{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T06:50:09Z","timestamp":1782370209524,"version":"3.54.5"},"reference-count":63,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"OnFoods","award":["PE00000003"],"award-info":[{"award-number":["PE00000003"]}]},{"name":"Italian Ministry of University and Research","award":["H93C22000630001"],"award-info":[{"award-number":["H93C22000630001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Apoptosis is a fundamental process for maintaining tissue homeostasis, and its dysregulation is closely linked to the development of numerous diseases, including colorectal cancer. In recent years, dietary polyphenols have gained interest due to their antioxidant, pro-apoptotic, and chemopreventive properties. Artichoke (Cynara scolymus L.) by-products are rich source of hydroxycinnamic acids and flavonoids, making them promising source of bioactive compounds. Methods: In this study we evaluated the cytotoxic and pro-apoptotic activity of four aqueous extracts obtained from artichoke bract by-products, including one commercial hybrid (CAPB) and three local Apulian varieties (BriB, VaMB, LMTB), in human colorectal adenocarcinoma cell lines (Caco-2 and HT29). The extracts were characterized according to their total polyphenol content and phenolic profile. Results: The selected artichoke by-product extracts exhibited significant cytotoxic effects both in a concentration- and time-dependent manner, with concentrations \u2265 2 mg\/mL significantly reducing cell viability and nearly abolishing it at 4 mg\/mL after 48 h. Moreover, treatment with the extracts modulated the expression of apoptosis-related proteins, characterized by an increase in pro-apoptotic markers (Bax, caspase-9, caspase-3) and a decrease in the anti-apoptotic protein Bcl-2, suggesting activation of the mitochondrial apoptotic pathway. In particular, the BriB extract was able to induce an apoptosis rate higher than 80% in Caco-2 cells and achieved comparable rates in HT29 cells at concentrations of 2\u20133 mg\/mL. Conclusions: Overall, these findings demonstrate that artichoke by-product extracts exert significant pro-apoptotic effects in colorectal cancer cells and highlight their potential as sustainable sources of bioactive compounds for nutraceutical or adjuvant anticancer applications.<\/jats:p>","DOI":"10.3390\/nu18132077","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T05:48:16Z","timestamp":1782366496000},"page":"2077","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phenolic-Rich Extracts from Artichoke By-Products Promote Apoptosis in Human Colorectal Cancer Cell Lines"],"prefix":"10.3390","volume":"18","author":[{"given":"Rosa","family":"Calvello","sequence":"first","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9851-3124","authenticated-orcid":false,"given":"Antonia","family":"Cianciulli","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Compierchio","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7526-6968","authenticated-orcid":false,"given":"Chiara","family":"Porro","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giusy Rita","family":"Caponio","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2010-884X","authenticated-orcid":false,"given":"Maria","family":"De Angelis","sequence":"additional","affiliation":[{"name":"Department of Soil, Plant and Food Sciences, University of Bari Aldo Moro, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5457-1069","authenticated-orcid":false,"given":"Maria Antonietta","family":"Panaro","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/01926230701320337","article-title":"Apoptosis: A review of programmed cell death","volume":"35","author":"Elmore","year":"2007","journal-title":"Toxicol. Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/s41580-018-0089-8","article-title":"Regulation of apoptosis in health and disease: The balancing act of BCL-2 family proteins","volume":"20","author":"Singh","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"863","DOI":"10.32604\/biocell.2021.013993","article-title":"Mechanisms adopted by cancer cells to escape apoptosis\u2013A review","volume":"45","author":"Dandoti","year":"2021","journal-title":"Biocell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.critrevonc.2005.06.005","article-title":"An overview of apoptosis and the prevention of colorectal cancer","volume":"57","author":"Alastair","year":"2006","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.drup.2009.02.002","article-title":"Targeting Apoptosis as an Approach for Gastrointestinal Cancer Therapy","volume":"12","author":"Qiao","year":"2009","journal-title":"Drug Resist. Updates"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Orlandi, G., Roncucci, L., Carnevale, G., and Sena, P. (2023). Different Roles of Apoptosis and Autophagy in the Development of Human Colorectal Cancer. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241210201"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/1475-2891-3-19","article-title":"Nutrition and cancer: A review of the evidence for an anti-cancer diet","volume":"3","author":"Donaldson","year":"2004","journal-title":"Nutr. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1177\/153537020623100201","article-title":"Targeting apoptosis with dietary bioactive agents","volume":"231","author":"Martin","year":"2006","journal-title":"Exp. Biol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.jff.2016.06.032","article-title":"Colon microbiota fermentation of dietary prebiotics towards short\u2014Chain fatty acids and their roles as anti-inflammatory and antitumor agents: A review","volume":"25","author":"Fernandez","year":"2016","journal-title":"J. Funct. Foods"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.amjms.2016.08.027","article-title":"Resveratrol inhibited non-small cell lung cancer through inhibiting STAT-3 signaling","volume":"352","author":"Li","year":"2016","journal-title":"Am. J. Medical. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Costea, T., Hudit, A., Ciolac, O.A., G\u0103l\u0103\u021beanu, B., Ginghin\u0103, O., Costache, M., Ganea, C., and Mocanu, M.M. (2018). Chemoprevention of Colorectal Cancer by Dietary Compounds. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19123787"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"114689","DOI":"10.1016\/j.jep.2021.114689","article-title":"Curcumin inhibits the invasion and metastasis of triple negative breast cancer via hedgehog\/Gli1 signaling pathway","volume":"283","author":"Li","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6483","DOI":"10.1002\/fsn3.3590","article-title":"The combined anticancer of peanut skin procyanidins and resveratrol to CACO-2 colorectal cancer cells","volume":"1","author":"Wang","year":"2023","journal-title":"Food Sci. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"C244","DOI":"10.1111\/j.1750-3841.2011.02531.x","article-title":"Polyphenol compounds in artichoke plant tissues and varieties","volume":"77","author":"Negro","year":"2012","journal-title":"J. Food Sci."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Porro, C., Benameur, T., Cianciulli, A., Vacca, M., Chiarini, M., De Angelis, M., and Panaro, M.A. (2024). Functional and Therapeutic Potential of Cynara scolymus in Health Benefits. Nutrients, 16.","DOI":"10.3390\/nu16060872"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1021\/jf020792b","article-title":"Analysis of antioxidative phenolic compounds in artichoke (Cynara scolymus L.)","volume":"51","author":"Wang","year":"2003","journal-title":"J. Agric. Food Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7272","DOI":"10.1021\/jf0490192","article-title":"Phenolic compounds from the leaf extract of artichoke (Cynara scolymus L.) and their antimicrobial activities","volume":"52","author":"Zhu","year":"2004","journal-title":"J. Agric. Food Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1080\/01635580801891583","article-title":"Antioxidative and apoptotic properties of polyphenolic extracts from edible part of artichoke (Cynara scolymus L.) on cultured rat hepatocytes and on human hepatoma cells","volume":"60","author":"Miccadei","year":"2008","journal-title":"Nutr. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s11130-015-0503-8","article-title":"Pharmacological Studies of Artichoke Leaf Extract and Their Health Benefits","volume":"70","author":"Affes","year":"2015","journal-title":"Plant Foods Hum. Nutr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5062","DOI":"10.1002\/jsfa.14232","article-title":"Phenolic characterization and nutraceutical evaluation of by-products from different globe artichoke cultivars","volume":"105","author":"Caponio","year":"2025","journal-title":"J. Sci. Food Agri."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1111\/ijfs.13486","article-title":"Enrichment of fresh pasta with antioxidant extracts obtained from artichoke canning by-products by ultrasound-assisted technology and quality characterisation of the end product","volume":"52","author":"Pasqualone","year":"2017","journal-title":"Int. J. Food Sci. Technol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.cofs.2016.02.002","article-title":"Dietary polyphenols, oxidative stress and antioxidant and anti-inflammatory effects","volume":"8","author":"Zhang","year":"2016","journal-title":"Curr. Opin. Food Sci."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Caponio, G.R., Minervini, F., Tamma, G., Gambacorta, G., and De Angelis, M. (2023). Promising application of grape pomace and its agri-food valorization: Source of bioactive molecules with beneficial effects. Sustainability, 15.","DOI":"10.3390\/su15119075"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"8459","DOI":"10.1039\/D4FO01395F","article-title":"Nutritional, antioxidant and biological activity characterization of orange peel flour to produce nutraceutical gluten-free muffins","volume":"15","author":"Caponio","year":"2024","journal-title":"Food Funct."},{"key":"ref_25","first-page":"109","article-title":"Anticancer properties of hydroxycinnamic acids-a review","volume":"1","author":"Rocha","year":"2012","journal-title":"Cancer Clin. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e2000073","DOI":"10.1002\/cbdv.202000073","article-title":"Chemical Composition, Antioxidant Potential and Enzymes Inhibitory Properties of Globe Artichoke By-Products","volume":"17","author":"Rejeb","year":"2020","journal-title":"Chem. Biodivers."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Caponio, G.R., Noviello, M., Calabrese, F.M., Gambacorta, G., Giannelli, G., and De Angelis, M. (2022). Effects of grape pomace polyphenols and in vitro gastrointestinal digestion on antimicrobial activity: Recovery of bioactive compounds. Antioxidants, 11.","DOI":"10.3390\/antiox11030567"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7965435","DOI":"10.1155\/2020\/7965435","article-title":"Artichoke Polyphenols Sensitize Human Breast Cancer Cells to Chemotherapeutic Drugs via a ROS-Mediated Downregulation of Flap Endonuclease 1","volume":"2020","author":"Mileo","year":"2020","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s43046-020-00026-4","article-title":"Anticancer effects induced by artichoke extract in oral squamous carcinoma cell lines","volume":"32","author":"Hassabou","year":"2020","journal-title":"J. Egypt. Natl. Canc. Inst."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Laghezza Masci, V., Alicandri, E., Antonelli, C., Paolacci, A.R., Marabottini, R., Tomassi, W., Scarascia Mugnozza, G., Tiezzi, A., Garzoli, S., and Vinciguerra, V. (2024). Cynara cardunculus L. var. scolymus L. Landrace \u201cCarciofo Ortano\u201d as a Source of Bioactive Compounds. Plants, 13.","DOI":"10.3390\/plants13060761"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Villarini, M., Acito, M., di Vito, R., Vannini, S., Dominici, L., Faigoni, C., Pagiotti, R., and Moretti, M. (2021). Pro-Apoptotic Activity of Artichoke Leaf Extracts in Human HT-29 and RKO Colon Cancer Cells. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18084166"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Bianchi, S., Acquaviva, R., Di Giacomo, C., Tomasello, B., Pappalardo, F., Pino, A., Naletova, I., Condorelli, D., La Mantia, A., and Barbagallo, I. (2026). Cynara cardunculus subsp. cardunculus (Wild Artichoke) Extract: Antimicrobial Activity and Cytotoxicity, Apoptosis Induction, and Chemosensitization in Colon Cancer Cells. Biology, 15.","DOI":"10.3390\/biology15060475"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s10565-006-0175-0","article-title":"In vitro models of intestinal epithelial cell differentiation","volume":"23","author":"Turck","year":"2007","journal-title":"Cell Biol. Toxicol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Verhoeckx, K., Cotter, P., v\u00e1n L\u00f3pez, I., Kleiveland, E.C., Lea, L., Mackie, A., Requena, T., Swiatecka, D., and Wichers, H. (2015). HT29 Cell Line. The Impact of Food Bioactives on Health, Springer.","DOI":"10.1007\/978-3-319-16104-4"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Mi\u0161kovi\u0107 \u0160poljari\u0107, K., \u0160elo, G., Pe\u0161ut, E., Martinovi\u0107, J., Planini\u0107, M., Ti\u0161ma, M., and Buci\u0107-Koji\u0107, A. (2023). Antioxidant and antiproliferative potentials of phenolic-rich extracts from biotransformed grape pomace in colorectal Cancer. BMC Complement. Med. Ther., 23.","DOI":"10.1186\/s12906-023-03852-w"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Caponio, G.R., Cofano, M., Lippolis, T., Gigante, I., De Nunzio, V., Difonzo, G., Noviello, M., Tarricone, L., Gambacorta, G., and Giannelli, G. (2022). Anti-Proliferative and Pro-Apoptotic Effects of Digested Aglianico Grape Pomace Extract in Human Colorectal Cancer Cells. Molecules, 27.","DOI":"10.3390\/molecules27206791"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3635","DOI":"10.1016\/j.yexcr.2007.06.018","article-title":"Three Distinct Stages of Apoptotic Nuclear Condensation Revealed by Time-Lapse Imaging, Biochemical and Electron Microscopy Analysis of Cell-Free Apoptosis","volume":"313","author":"Sugimoto","year":"2007","journal-title":"Exp. Cell Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/B978-0-12-385493-3.00004-8","article-title":"Apoptosis and Beyond: Cytometry in Studies of Programmed Cell Death","volume":"3","author":"Wlodkowic","year":"2011","journal-title":"Methods Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"631","DOI":"10.7314\/APJCP.2013.14.2.631","article-title":"Comparative studies to evaluate relative in vitro potency of luteolin in inducing cell cycle arrest and apoptosis in HaCaT and A375 cells","volume":"14","author":"George","year":"2013","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Pei, S.N., Lee, K.T., Rau, K.M., Lin, T.Y., Tsai, T.H., and Hsu, Y.C. (2024). Luteolin (LUT) Induces Apoptosis and Regulates Mitochondrial Membrane Potential to Inhibit Cell Growth in Human Cervical Epidermoid Carcinoma Cells (Ca Ski). Biomedicines, 12.","DOI":"10.3390\/biomedicines12102330"},{"key":"ref_41","first-page":"1","article-title":"Luteolin promotes apoptotic cell death via upregulation of Nrf2 expression by DNA demethylase and the interaction of Nrf2 with p53 in human colon cancer cells","volume":"51","author":"Kang","year":"2019","journal-title":"Exp. Mol. Med."},{"key":"ref_42","first-page":"130","article-title":"Cancer chemopreventive potential of luteolin-7-O-glucoside isolated from Ophiorrhiza mungos Linn","volume":"63","author":"Baskar","year":"2011","journal-title":"Nutr. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1002\/tox.23319","article-title":"Luteolin-7-O-glucoside inhibits cell proliferation and modulates apoptosis through the AKT signaling pathway in human nasopharyngeal carcinoma","volume":"36","author":"Ho","year":"2021","journal-title":"Environ. Toxicol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Rahmani, A.H., Alsahli, M.A., Almatroudi, A., Almogbel, M.A., Khan, A.A., Anwar, S., and Almatroodi, S.A. (2022). The Potential Role of Apigenin in Cancer Prevention and Treatment. Molecules, 27.","DOI":"10.3390\/molecules27186051"},{"key":"ref_45","first-page":"131","article-title":"Apigenin as a bioactive compound for longevity: Targets and mechanisms in senescent cells","volume":"9","author":"Chaiyasit","year":"2026","journal-title":"Bioact. Compd. Health Dis."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Salehi, B., Venditti, A., Sharifi-Rad, M., Kr\u0119giel, D., Sharifi-Rad, J., Durazzo, A., Lucarini, M., Santini, A., Souto, E.B., and Novellino, E. (2019). The Therapeutic Potential of Apigenin. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20061305"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Tommonaro, G., De Simone, G., Iodice, C., Allar\u00e0, M., and Cutignano, A. (2025). A Phytochemical and Biological Characterization of Cynara cardunculus L. subsp. scolymus Cultivar \u201cCarciofo di Procida\u201d, a Traditional Italian Agri-Food Product (PAT) of the Campania Region. Molecules, 30.","DOI":"10.3390\/molecules30153285"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"102144","DOI":"10.1016\/j.redox.2021.102144","article-title":"Apigenin enhances apoptosis induction by 5-fluorouracil through regulation of thymidylate synthase in colorectal cancer cells","volume":"47","author":"Yang","year":"2021","journal-title":"Redox Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4521","DOI":"10.7150\/jca.34374","article-title":"The Power of Phytochemicals Combination in Cancer Chemoprevention","volume":"11","author":"Rizeq","year":"2020","journal-title":"J. Cancer"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"703","DOI":"10.7150\/jca.7235","article-title":"Simultaneous inhibition of cell-cycle, proliferation, survival, metastatic pathways and induction of apoptosis in breast cancer cells by a phytochemical super-cocktail: Genes that underpin its mode of action","volume":"4","author":"Ouhtit","year":"2013","journal-title":"J. Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Aromokeye, R., and Si, H. (2022). Combined Curcumin and Luteolin Synergistically Inhibit Colon Cancer Associated with Notch1 and TGF-\u03b2 Signaling Pathways in Cultured Cells and Xenograft Mice. Cancers, 14.","DOI":"10.3390\/cancers14123001"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1080\/01635581.2012.725194","article-title":"Resveratrol and quercetin in combination have anticancer activity in colon cancer cells and repress oncogenic microRNA-27a","volume":"65","author":"Banerjee","year":"2013","journal-title":"Nutr. Cancer"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"863","DOI":"10.2217\/fca.12.58","article-title":"Mitochondrial Membrane Permeabilization and Cell Death during Myocardial Infarction: Roles of Calcium and Reactive Oxygen Species","volume":"8","author":"Webster","year":"2012","journal-title":"Future Cardiol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Wani, A.K., Akhtar, N., Mir, T.U.G., Singh, R., Jha, P.K., Mallik, S.K., Sinha, S., Tripathi, S.K., Jai, A., and Jha, A. (2023). Targeting Apoptotic Pathway of Cancer Cells with Phytochemicals and Plant-Based Nanomaterials. Biomolecules, 13.","DOI":"10.3390\/biom13020194"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3301","DOI":"10.1002\/jcp.24029","article-title":"Artichoke polyphenols induce apoptosis and decrease the invasive potential of the human breast cancer cell line MDA-MB231","volume":"227","author":"Mileo","year":"2012","journal-title":"J. Cell Physiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"6791","DOI":"10.7314\/APJCP.2013.14.11.6791","article-title":"In vitro investigation of cytotoxic and apoptotic effects of Cynara L. species in colorectal cancer cells","volume":"14","author":"Simsek","year":"2013","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1038\/s12276-025-01470-9","article-title":"Caspases as master regulators of programmed cell death: Apoptosis, pyroptosis and beyond","volume":"57","author":"Dho","year":"2025","journal-title":"Exp. Mol. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1002\/ptr.2263","article-title":"Growth inhibitory effect of ethyl acetate-soluble fraction of Cynara cardunculus L. in leukemia cells involves cell cycle arrest, cytochrome c release and activation of caspases","volume":"22","author":"Nadova","year":"2008","journal-title":"Phytother. Res."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Zein, N., Yassin, F.A., Rashad, M., Talaat, E., and Abd Elhameed, H.A.H. (2026). Artichoke Extract Ameliorates CCl4-Induced Hepatocellular Carcinoma in Albino Rats by Regulating the Phosphatidylinositol 3-kinase\/serine-threonine Protein Kinase Pathway. Anticancer Agents Med. Chem., Epub ahead of printing.","DOI":"10.2174\/0118715206397860251023042637"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2948","DOI":"10.1002\/fsn3.1150","article-title":"Antiproliferative and cytotoxic effects of grape pomace and grape seed extracts on colorectal cancer cell lines","volume":"7","author":"Alguacil","year":"2019","journal-title":"Food Sci. Nutr."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"6467","DOI":"10.1021\/acs.jafc.6b04933","article-title":"Hydroxytyrosol and the Colonic Metabolites Derived from Virgin Olive Oil Intake Induce Cell Cycle Arrest and Apoptosis in Colon Cancer Cells","volume":"65","author":"Motilva","year":"2017","journal-title":"J. Agric. Food Chem."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Jim\u00e9nez-Moreno, N., Cimminelli, M.J., Volpe, F., Ans\u00f3, R., Esparza, I., M\u00e1rmol, I., Rodr\u00edguez-Yoldi, M.J., and Anc\u00edn-Azpilicueta, C. (2019). Phenolic Composition of Artichoke Waste and its Antioxidant Capacity on Differentiated Caco-2 Cells. Nutrients, 11.","DOI":"10.3390\/nu11081723"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Laghezza Masci, V., Mezzani, I., Alicandri, E., Tomassi, W., Paolacci, A.R., Covino, S., Vinciguerra, V., Catalani, E., Cervia, D., and Ciaffi, M. (2025). The Role of Extracts of Edible Parts and Production Wastes of Globe Artichoke (Cynara cardunculus L. var. Scolymus (L.)) in Counteracting Oxidative Stress. Antioxidants, 14.","DOI":"10.3390\/antiox14010116"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/13\/2077\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T06:29:49Z","timestamp":1782368989000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/13\/2077"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,25]]},"references-count":63,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["nu18132077"],"URL":"https:\/\/doi.org\/10.3390\/nu18132077","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,25]]}}}