{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:42:58Z","timestamp":1785404578017,"version":"3.56.0"},"reference-count":78,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007706","name":"Ministry of Economic Development","doi-asserted-by":"publisher","award":["SCORELINE"],"award-info":[{"award-number":["SCORELINE"]}],"id":[{"id":"10.13039\/501100007706","id-type":"DOI","asserted-by":"publisher"}]},{"award":["SCORELINE"],"award-info":[{"award-number":["SCORELINE"]}],"id":[{"id":"https:\/\/ror.org\/011z3ff80","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004913","name":"University of Palermo","doi-asserted-by":"publisher","award":["FFR 2026"],"award-info":[{"award-number":["FFR 2026"]}],"id":[{"id":"10.13039\/501100004913","id-type":"DOI","asserted-by":"publisher"}]},{"award":["FFR 2026"],"award-info":[{"award-number":["FFR 2026"]}],"id":[{"id":"https:\/\/ror.org\/044k9ta02","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Ministry of Universities and Research","award":["NextGenerationEU; Project code CN_00000033"],"award-info":[{"award-number":["NextGenerationEU; Project code CN_00000033"]}]},{"award":["NextGenerationEU; Project code CN_00000033"],"award-info":[{"award-number":["NextGenerationEU; Project code CN_00000033"]}],"id":[{"id":"https:\/\/ror.org\/0341vw408","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Seed oils from Sicilian white (WGSO) and red grapes (RGSO) were examined for their possible cytotoxic effect on HepG2 liver and CaCo-2 colorectal cancer cells, the latter also induced to intestinal differentiation. Half maximal inhibitory dilution (ID50) values were obtained from viability assays, excluding RGSO-treated HepG2 and differentiated CaCo-2 cells exposed to both oils, which were unresponsive. Cell morphology and cycle status, reactive oxygen species (ROS) production, and the levels of cytoprotection, regulated cell death (RCD), and autophagy markers were evaluated. No occurrence of canonical apoptosis was proven in any experimental condition. In HepG2 cells, WGSO ID50 primarily triggered autophagy collapse, as evidenced by modulation of Beclin-1, p62 and LC3 markers, initiating a cascade of metabolic disturbances that led to oxidative stress reaction and mild inflammatory signaling. In CaCo-2 cells, WGSO ID50 mainly elicited a strong ROS-mediated cell injury without major alterations in autophagy, with transient activation but incomplete execution of pyroptotic and necroptotic effectors (gasdermin-D, pMLKL and HMGB1). In the same cells, RGSO ID50 induced a weaker metabolic perturbation with transient activation of multiple RCD pathways and concomitant autophagy inhibition. Research findings revealed distinct damage-inducing properties linked to oils\u2019 chemical profiles, underscoring their prospective utilization as beneficial bioactive supplements.<\/jats:p>","DOI":"10.3390\/molecules31101567","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T19:35:43Z","timestamp":1778528143000},"page":"1567","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cytotoxic Activity of Sicilian Red- and White-Grape Seed Oils on Human Liver and Colorectal Cancer Cells"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-1170-931X","authenticated-orcid":false,"given":"Daniela","family":"Ganci","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Universit\u00e0 di Palermo, 90128 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2518-6716","authenticated-orcid":false,"given":"Giulia","family":"Abruscato","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Universit\u00e0 di Palermo, 90128 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8381-3389","authenticated-orcid":false,"given":"Roberto","family":"Chiarelli","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Universit\u00e0 di Palermo, 90128 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1363-1381","authenticated-orcid":false,"given":"Manuela","family":"Mauro","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Universit\u00e0 di Palermo, 90128 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8772-7143","authenticated-orcid":false,"given":"Vincenzo","family":"Arizza","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Universit\u00e0 di Palermo, 90128 Palermo, Italy"},{"name":"NBFC\u2014National Biodiversity Future Center, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6437-9409","authenticated-orcid":false,"given":"Mirella","family":"Vazzana","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Universit\u00e0 di Palermo, 90128 Palermo, Italy"},{"name":"NBFC\u2014National Biodiversity Future Center, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9821-5891","authenticated-orcid":false,"given":"Claudio","family":"Luparello","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Universit\u00e0 di Palermo, 90128 Palermo, Italy"},{"name":"NBFC\u2014National Biodiversity Future Center, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3956","DOI":"10.1021\/acsfoodscitech.5c00519","article-title":"From Waste to Worth: Transforming Winemaking Residues into High-Value Ingredients","volume":"5","author":"Ratto","year":"2025","journal-title":"ACS Food Sci. Technol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2812","DOI":"10.1021\/jf803627t","article-title":"Characterization of oil obtained from grape seeds collected during berry development","volume":"57","author":"Rubio","year":"2009","journal-title":"J. Agric. Food Chem."},{"key":"ref_3","first-page":"629","article-title":"Seed Oil Content and Selected Qualitative Parameters of Oils from Grape Seeds","volume":"11","author":"Burg","year":"2017","journal-title":"Potravin. Slovak J. Food Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"59","DOI":"10.4137\/NMI.S32910","article-title":"Grape Seed Oil Compounds: Biological and Chemical Actions for Health","volume":"9","author":"Garavaglia","year":"2016","journal-title":"Nutr. Metab. Insights"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"S\u0142awi\u0144ska, N., and Olas, B. (2023). Selected Seeds as Sources of Bioactive Compounds with Diverse Biological Activities. Nutrients, 15.","DOI":"10.3390\/nu15010187"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"114017","DOI":"10.1016\/j.biopha.2022.114017","article-title":"Targeting apoptosis in MCF-7 and Ehrlich ascites carcinoma cells by saponifiable fractions from green and black Vitis vinifera seed oil","volume":"157","author":"Shaban","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Shaalan, A.A.M., Elmorsy, E.M., Embaby, E.M., Alfawaz, M., Aly, N.M., Shams, A.S., Fawzy, M.S., and Hosny, N. (2025). Antitumor, Antioxidant, and Hepatoprotective Effects of Grape Seed Oil Nanoemulsion as a Dietary Phytochemical Intervention in Ehrlich Solid Tumors. Nutrients, 17.","DOI":"10.3390\/nu17213450"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"105698","DOI":"10.1016\/j.archoralbio.2023.105698","article-title":"Cancer chemo-preventive role of grape seed oil and cisplatin as a combination adjuvant therapy in the treatment of tongue squamous cell carcinoma: A biological in-vitro study","volume":"151","author":"Labah","year":"2023","journal-title":"Arch. Oral Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"12018","DOI":"10.1038\/s41598-026-44404-9","article-title":"Unsaponifiable fraction of black Vitis vinifera seed oil attenuates liver cancer progression by targeting apoptosis and key tumor-associated genes: In vitro, in vivo, and in silico studies","volume":"16","author":"Ahmad","year":"2026","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Ganci, D., Bellistr\u00ec, F., Mauro, M., Chiarelli, R., Longo, F., Indelicato, S., Indelicato, S., Laudicina, V.A., Arizza, V., and Vazzana, M. (2025). Valorization of Winemaking By-Products: White and Red Grape Seed Oils Improve Glucose Consumption and Uptake In Vitro. Molecules, 30.","DOI":"10.3390\/molecules30091933"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Agaj, A., Per\u0161uri\u0107, \u017d., and Paveli\u0107, S.K. (2022). Mediterranean Food Industry By-Products as a Novel Source of Phytochemicals with a Promising Role in Cancer Prevention. Molecules, 27.","DOI":"10.3390\/molecules27248655"},{"key":"ref_12","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_13","first-page":"178","article-title":"Targeting apoptosis pathways in cancer therapy","volume":"55","author":"Ghobrial","year":"2005","journal-title":"CA Cancer J. Clin."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.tcb.2017.05.005","article-title":"Gasdermins: Effectors of Pyroptosis","volume":"27","author":"Kovacs","year":"2017","journal-title":"Trends Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Martinez-Osorio, V., Abdelwahab, Y., and Ros, U. (2023). The Many Faces of MLKL, the Executor of Necroptosis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241210108"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ntuli, T.M. (2015). HMGB1 in cell death. Cell Death\u2014Autophagy, Apoptosis and Necrosis, IntechOpen.","DOI":"10.5772\/59648"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.immuni.2020.06.019","article-title":"Snapshot of a Deadly Embrace: The Caspase-1-GSDMD Interface","volume":"53","author":"Lamkanfi","year":"2020","journal-title":"Immunity"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1124\/jpet.106.101808","article-title":"Geldanamycin, an inhibitor of Hsp90, potentiates cytochrome P4502E1-mediated toxicity in HepG2 cells","volume":"317","author":"Dey","year":"2006","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"68976","DOI":"10.18632\/oncotarget.12185","article-title":"Hsp60 exerts a tumor suppressor function by inducing cell differentiation and inhibiting invasion in hepatocellular carcinoma","volume":"7","author":"Zhang","year":"2016","journal-title":"Oncotarget"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"47","DOI":"10.5483\/BMBRep.2013.46.1.037","article-title":"Heat shock protein 90\u03b2 inhibits apoptosis of intestinal epithelial cells induced by hypoxia through stabilizing phosphorylated Akt","volume":"46","author":"Zhang","year":"2013","journal-title":"BMB Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.lfs.2010.02.010","article-title":"Overexpression of a 60-kDa heat shock protein enhances cytoprotective function of small intestinal epithelial cells","volume":"86","author":"Takada","year":"2010","journal-title":"Life Sci."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"de Haro, J.C., Rodr\u00edguez, J.F., Carmona, M., and P\u00e9rez, \u00c1. (2018). Revalorization of Grape Seed Oil for Innovative Non-Food Applications. Grapes and Wines\u2014Advances in Production, Processing, Analysis and Valorization, InTech. Available online: https:\/\/www.intechopen.com\/chapters\/58129.","DOI":"10.5772\/intechopen.71710"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Martin, M.E., Grao-Cruces, E., Millan-Linares, M.C., and Montserrat-de la Paz, S. (2020). Grape (Vitis vinifera L.) Seed Oil: A Functional Food from the Winemaking Industry. Foods, 9.","DOI":"10.3390\/foods9101360"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Di Pietro Fernandes, C., Santana, L.F., dos Santos, J.R., Fernandes, D.S., Hiane, P.A., Pott, A., de C\u00e1ssia Freitas, K., Bogo, D., do Nascimento, V.A., and de Oliveira Fili\u00fa, W.F. (2023). Nutraceutical Potential of Grape (Vitis vinifera L.) Seed Oil in Oxidative Stress, Inflammation, Obesity and Metabolic Alterations. Molecules, 28.","DOI":"10.3390\/molecules28237811"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2708","DOI":"10.1002\/eji.202170126","article-title":"Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)","volume":"51","author":"Cossarizza","year":"2021","journal-title":"Eur. J. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"39544","DOI":"10.18632\/oncotarget.9647","article-title":"Prognostic value of the autophagy markers LC3 and p62\/SQSTM1 in early-stage non-small cell lung cancer","volume":"7","author":"Adams","year":"2016","journal-title":"Oncotarget"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s00432-017-2557-5","article-title":"Targeting LC3 and Beclin-1 autophagy genes suppresses proliferation, survival, migration and invasion by inhibition of Cyclin-D1 and uPAR\/Integrin \u03b21\/ Src signaling in triple negative breast cancer cells","volume":"144","author":"Hamurcu","year":"2018","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"377","DOI":"10.7555\/JBR.30.20150137","article-title":"Complex role of autophagy in regulation of hepatic lipid and lipoprotein metabolism","volume":"31","author":"Zamani","year":"2017","journal-title":"J. Biomed. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1016\/j.jhep.2022.05.015","article-title":"Lack of hepatic autophagy promotes severity of liver injury but not steatosis","volume":"77","author":"Ding","year":"2022","journal-title":"J. Hepatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.addr.2009.02.003","article-title":"Induction of heat shock proteins for protection against oxidative stress","volume":"61","author":"Kalmar","year":"2009","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Pastorek, M., Muller, P., Coates, P.J., and Vojtesek, B. (2018). Intrinsic proteotoxic stress levels vary and act as a predictive marker for sensitivity of cancer cells to Hsp90 inhibition. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0202758"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"116284","DOI":"10.1016\/j.biopha.2024.116284","article-title":"Autophagy regulation and redox perturbation by transcrocetin suppress the growth of endometriosis","volume":"173","author":"Ham","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"749","DOI":"10.2147\/JIR.S277457","article-title":"Role of Caspase-1 in the Pathogenesis of Inflammatory-Associated Chronic Noncommunicable Diseases","volume":"13","author":"Molla","year":"2020","journal-title":"J. Inflamm. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1186\/s12974-018-1235-0","article-title":"Necroptosis: A regulated inflammatory mode of cell death","volume":"15","author":"Dhuriya","year":"2018","journal-title":"J. Neuroinflammation"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"476","DOI":"10.2119\/2008-00034.Klune","article-title":"HMGB1: Endogenous danger signaling","volume":"14","author":"Klune","year":"2008","journal-title":"Mol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Simpson, J., Spann, K.M., and Phipps, S. (2022). MLKL Regulates Rapid Cell Death-independent HMGB1 Release in RSV Infected Airway Epithelial Cells. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.890389"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"120032","DOI":"10.1016\/j.bbamcr.2025.120032","article-title":"HMGB1 activates caspase-1 and induces hepatic stellate cell activation via GABPA-ASC","volume":"1872","author":"Jing","year":"2025","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1038\/s41590-023-01526-w","article-title":"Molecular mechanisms of gasdermin D pore-forming activity","volume":"24","author":"Devant","year":"2023","journal-title":"Nat. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.molcel.2010.09.023","article-title":"Autophagy and the integrated stress response","volume":"40","author":"Kroemer","year":"2010","journal-title":"Mol. Cell."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.tcb.2023.07.005","article-title":"Sublethal engagement of apoptotic pathways in residual cancer","volume":"34","author":"Killarney","year":"2024","journal-title":"Trends Cell Biol."},{"key":"ref_41","first-page":"5371","article-title":"Antiproliferative, antioxidant and anti-inflammatory effects of hydroxytyrosol on human hepatoma HepG2 and Hep3B cell lines","volume":"32","author":"Tutino","year":"2012","journal-title":"Anticancer Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"7726","DOI":"10.3748\/wjg.v19.i43.7726","article-title":"Events associated with apoptotic effect of p-Coumaric acid in HCT-15 colon cancer cells","volume":"19","author":"Jaganathan","year":"2013","journal-title":"World J. Gastroenterol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1007\/BF02972984","article-title":"Role of NADPH oxidase-mediated generation of reactive oxygen species in the mechanism of apoptosis induced by phenolic acids in HepG2 human hepatoma cells","volume":"28","author":"Lee","year":"2005","journal-title":"Arch. Pharmacal Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.ejphar.2015.09.044","article-title":"The effects of caffeic, coumaric and ferulic acids on proliferation, superoxide production, adhesion and migration of human tumor cells in vitro","volume":"766","author":"Kovacic","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"533","DOI":"10.3892\/ijo.2017.4049","article-title":"Oleocanthal exerts antitumor effects on human liver and colon cancer cells through ROS generation","volume":"51","author":"Cusimano","year":"2017","journal-title":"Int. J. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1177\/0960327119839173","article-title":"Syringic acid triggers reactive oxygen species-mediated cytotoxicity in HepG2 cells","volume":"38","author":"Gheena","year":"2019","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"66","DOI":"10.3892\/etm.2021.10989","article-title":"Protective effects of syringic acid on inflammation, apoptosis and intestinal barrier function in Caco-2 cells following oxygen-glucose deprivation\/reoxygenation-induced injury","volume":"23","author":"Xiang","year":"2022","journal-title":"Exp. Ther. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.intimp.2017.05.026","article-title":"Rutin exhibits hepatoprotective effects in a mouse model of non-alcoholic fatty liver disease by reducing hepatic lipid levels and mitigating lipid-induced oxidative injuries","volume":"49","author":"Liu","year":"2017","journal-title":"Int. Immunopharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3595","DOI":"10.7150\/ijbs.62471","article-title":"Rutin attenuates Sorafenib-induced Chemoresistance and Autophagy in Hepatocellular Carcinoma by regulating BANCR\/miRNA-590-5P\/OLR1 Axis","volume":"17","author":"Zhou","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1247\/csf.15.393","article-title":"Flavonoids inhibit the expression of heat shock proteins","volume":"15","author":"Hosokawa","year":"1990","journal-title":"Cell Struct. Funct."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1089\/jmf.2019.0098","article-title":"Assessing Anticancer Potential of Blueberry Flavonoids, Quercetin, Kaempferol, and Gentisic Acid, Through Oxidative Stress and Apoptosis Parameters on HCT-116 Cells","volume":"22","author":"Sezer","year":"2019","journal-title":"J. Med. Food"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"579","DOI":"10.2147\/OTT.S460359","article-title":"Mechanistic Insight into the Autophagic and Apoptotic Activity of Kaempferol on Liver Cancer Cells","volume":"17","author":"Sharma","year":"2024","journal-title":"OncoTargets Ther."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Parra-Perez, A.M., P\u00e9rez-Jim\u00e9nez, A., Gris-C\u00e1rdenas, I., Bonel-P\u00e9rez, G.C., Carrasco-D\u00edaz, L.M., Mokhtari, K., Garc\u00eda-Salguero, L., Lupi\u00e1\u00f1ez, J.A., and Rufino-Palomares, E.E. (2022). Involvement of the PI3K\/AKT Intracellular Signaling Pathway in the AntiCancer Activity of Hydroxytyrosol, a Polyphenol from Olea europaea, in Hematological Cells and Implication of HSP60 Levels in Its Anti-Inflammatory Activity. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23137053"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.ejphar.2018.10.003","article-title":"Ferulic Acid exerts concentration-dependent anti-apoptotic and neuronal differentiation-inducing effects in PC12 and mouse neural stem cells","volume":"841","author":"Moghadam","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/s12935-018-0595-y","article-title":"The anticancer effects of ferulic acid is associated with induction of cell cycle arrest and autophagy in cervical cancer cells","volume":"18","author":"Gao","year":"2018","journal-title":"Cancer Cell Int."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"9293416","DOI":"10.1155\/2019\/9293416","article-title":"2-Methoxyestradiol and Its Combination with a Natural Compound, Ferulic Acid, Induces Melanoma Cell Death via Downregulation of Hsp60 and Hsp90","volume":"2019","author":"Kamm","year":"2019","journal-title":"J. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"902","DOI":"10.2174\/0113892010303032240902063213","article-title":"Ferulic Acid Regulates GSDMD through the ROS\/JNK\/Bax Mitochondrial Apoptosis Pathway to Induce Pyroptosis in Lung Cancer","volume":"26","author":"Liu","year":"2025","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Goren, L., Zhang, G., Kaushik, S., Breslin, P.A.S., Du, Y.N., and Foster, D.A. (2019). (-)-Oleocanthal and (-)-oleocanthal-rich olive oils induce lysosomal membrane permeabilization in cancer cells. PLoS ONE, 14.","DOI":"10.1101\/610097"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/s11060-017-2387-y","article-title":"Rutin increases the cytotoxicity of temozolomide in glioblastoma via autophagy inhibition","volume":"132","author":"Zhang","year":"2017","journal-title":"J. Neurooncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"6063","DOI":"10.1007\/s11033-022-07395-0","article-title":"Rutin protects rat liver and kidney from sodium valproate-induce damage by attenuating oxidative stress, ER stress, inflammation, apoptosis and autophagy","volume":"49","author":"Kandemir","year":"2022","journal-title":"Mol. Biol. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"110646","DOI":"10.1016\/j.compbiomed.2025.110646","article-title":"Kaempferol enhances immunogenic cell death via premortem stress and necroptosis in cholangiocarcinoma: Insights from network pharmacology and mechanistic studies","volume":"195","author":"Putri","year":"2025","journal-title":"Comput. Biol. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e14385","DOI":"10.1111\/cbdd.14385","article-title":"Kaempferol exerts antioxidant effects in age-related diminished ovarian reserve by regulating the HSP90\/NRF2 pathway","volume":"103","author":"Hua","year":"2024","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Cicio, A., Sut, S., Dall\u2019Acqua, S., Bruno, M., Luparello, C., Serio, R., and Zizzo, M.G. (2023). Chemical Characterization and Cytotoxic and Antioxidant Activity Evaluation of the Ethanol Extract from the Bulbs of Pancratium maritimun Collected in Sicily. Molecules, 28.","DOI":"10.3390\/molecules28103986"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Abruscato, G., Ganci, D., Bellistr\u00ec, F., Chiarelli, R., Mauro, M., Vizzini, A., Arizza, V., Vazzana, M., and Luparello, C. (2025). Anti-Inflammatory and Immunomodulatory Effects of Aqueous Extracts from Green Leaves and Rhizomes of Posidonia oceanica (L.) Delile on LPS-Stimulated RAW 264.7 Macrophages. Molecules, 30.","DOI":"10.3390\/molecules30244685"},{"key":"ref_65","first-page":"722","article-title":"Cytotoxic capability and the associated proteomic profile of cell-free coelomic fluid extracts from the edible sea cucumber Holothuria tubulosa on HepG2 liver cancer cells","volume":"21","author":"Luparello","year":"2022","journal-title":"EXCLI J."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Abruscato, G., Chiarelli, R., Lazzara, V., Punginelli, D., Sug\u00e1r, S., Mauro, M., Librizzi, M., Di Stefano, V., Arizza, V., and Luparello, C. (2023). In Vitro Cytotoxic Effect of Aqueous Extracts from Leaves and Rhizomes of the Seagrass Posidonia oceanica (L.) Delile on HepG2 Liver Cancer Cells: Focus on Autophagy and Apoptosis. Biology, 12.","DOI":"10.3390\/biology12040616"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/nature14190","article-title":"Nutrient-sensing mechanisms and pathways","volume":"517","author":"Efeyan","year":"2015","journal-title":"Nature"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.cell.2017.02.004","article-title":"mTOR Signaling in Growth, Metabolism, and Disease","volume":"168","author":"Saxton","year":"2017","journal-title":"Cell"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.tifs.2014.05.003","article-title":"Resveratrol Encapsulation: Designing Delivery Systems to Overcome Solubility, Stability and Bioavailability Issues","volume":"38","author":"McClements","year":"2014","journal-title":"Trends Food Sci. Technol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Pateiro, M., G\u00f3mez, B., Munekata, P.E., Barba, F.J., Putnik, P., Kova\u010devi\u0107, D.B., and Lorenzo, J.M. (2021). Nanoencapsulation of promising bioactive compounds to improve their absorption, stability, functionality and the appearance of the final food products. Molecules, 26.","DOI":"10.3390\/molecules26061547"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Costa, M., Sezgin-Bayindir, Z., Losada-Barreiro, S., Paiva-Martins, F., Saso, L., and Bravo-D\u00edaz, C. (2021). Polyphenols as antioxidants for extending food shelf-life and in the prevention of health diseases: Encapsulation and interfacial phenomena. Biomedicines, 9.","DOI":"10.3390\/biomedicines9121909"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s12393-015-9115-1","article-title":"Encapsulation of Functional Lipophilic Food and Drug Biocomponents","volume":"7","author":"Dima","year":"2015","journal-title":"Food Eng. Rev."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s10311-017-0663-x","article-title":"Encapsulation of bioactive compounds using nanoemulsions","volume":"16","author":"Sarkar","year":"2018","journal-title":"Environ. Chem. Lett."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"3362","DOI":"10.1080\/10408398.2021.1987858","article-title":"Potential micro-\/nano-encapsulation systems for improving stability and bioavailability of anthocyanins: An updated review","volume":"63","author":"Rashwan","year":"2023","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Klojdov\u00e1, I., Milota, T., Smetanov\u00e1, J., and Stathopoulos, C. (2023). Encapsulation: A strategy to deliver therapeutics and bioactive compounds?. Pharmaceuticals, 16.","DOI":"10.3390\/ph16030362"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Hao, M., Tan, X., Liu, K., and Xin, N. (2026). Nanoencapsulation of nutraceuticals: Enhancing stability and bioavailability in functional foods. Front. Nutr., 12.","DOI":"10.3389\/fnut.2025.1746176"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/10408398.2014.971353","article-title":"A comprehensive overview on the micro- and nano-technological encapsulation advances for enhancing the chemical stability and bioavailability of carotenoids","volume":"58","author":"Soukoulis","year":"2018","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4103\/mtsp.mtsp_1_24","article-title":"Advancements in Nutraceutical Delivery: Integrating Nanotechnology and Microencapsulation for Enhanced Efficacy and Bioavailability","volume":"8","author":"Gul","year":"2024","journal-title":"Matrix Sci. Pharma"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/10\/1567\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T04:27:52Z","timestamp":1779251272000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/10\/1567"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,8]]},"references-count":78,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["molecules31101567"],"URL":"https:\/\/doi.org\/10.3390\/molecules31101567","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,8]]}}}