{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T19:37:17Z","timestamp":1789069037508,"version":"build-2803163510"},"reference-count":73,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Xeda International S.A.S."},{"name":"Italian Ministry for Research","award":["RFO 2024"],"award-info":[{"award-number":["RFO 2024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Colorectal cancer is one of the leading causes of cancer-associated mortality, and multifactorial resistance remains one of the main challenges in its treatment. Essential oils and their main compounds show interesting anticancer properties, but their mechanism of action is yet to be defined. This study aims to assess the cytotoxic effects of eugenol (EU) and cinnamaldehyde (CN) on colorectal cancer (CRC) cells, highlighting possible mechanisms of action. These compounds were tested on normal immortalized colonocytes (NCM-460) and two CRC cell lines: Caco-2, a human colon epithelial adenocarcinoma cell line, and SW-620, colon cancer cells derived from a lymph node metastatic site. The efficacy of EU and CN was evaluated through CellTiter-Glo\u00ae and clonogenic assays and by determining proinflammatory cytokine secretion. Transcriptome analysis was used to identify possible pathways affected by EU and CN treatments. The results confirmed that EU and CN were selectively cytotoxic and pro-apoptotic against CRC cells, with different putative mechanisms. While EU drove cytotoxicity through robust transcriptional remodeling, CN yielded a stronger anti-inflammatory action. We confirmed that EU and CN are promising natural candidates in CRC prevention and treatment, even in association with chemotherapeutic drugs.<\/jats:p>","DOI":"10.3390\/ijms27020649","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T15:33:16Z","timestamp":1767886396000},"page":"649","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Investigating the Molecular Mechanisms of the Anticancer Effects of Eugenol and Cinnamaldehyde Against Colorectal Cancer (CRC) Cells In Vitro"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5316-5112","authenticated-orcid":false,"given":"Alberto","family":"Bernacchi","sequence":"first","affiliation":[{"name":"Department of Biological, Geological, and Environmental Sciences (BiGeA), University of Bologna, Via Selmi 3, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Chiara","family":"Valerii","sequence":"additional","affiliation":[{"name":"Department of Biological, Geological, and Environmental Sciences (BiGeA), University of Bologna, Via Selmi 3, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1870-7536","authenticated-orcid":false,"given":"Renato","family":"Spigarelli","sequence":"additional","affiliation":[{"name":"Department of Biological, Geological, and Environmental Sciences (BiGeA), University of Bologna, Via Selmi 3, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1338-9361","authenticated-orcid":false,"given":"Nikolas Kostantine","family":"Dussias","sequence":"additional","affiliation":[{"name":"Inflammatory Bowel Disease (IBD) Unit, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Azienda Ospedaliero-Universitaria di Bologna, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy"},{"name":"Department of Medical and Surgical and Sciences, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Rizzello","sequence":"additional","affiliation":[{"name":"Inflammatory Bowel Disease (IBD) Unit, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Azienda Ospedaliero-Universitaria di Bologna, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy"},{"name":"Department of Medical and Surgical and Sciences, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8525-2981","authenticated-orcid":false,"given":"Enzo","family":"Spisni","sequence":"additional","affiliation":[{"name":"Department of Biological, Geological, and Environmental Sciences (BiGeA), University of Bologna, Via Selmi 3, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/s41392-024-01953-7","article-title":"Signaling Pathways Involved in Colorectal Cancer: Pathogenesis and Targeted Therapy","volume":"9","author":"Li","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Marcellinaro, R., Spoletini, D., Grieco, M., Avella, P., Cappuccio, M., Troiano, R., Lisi, G., Garbarino, G.M., and Carlini, M. (2023). Colorectal Cancer: Current Updates and Future Perspectives. J. Clin. Med., 13.","DOI":"10.20944\/preprints202310.1321.v1"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Tang, Y., and Fan, Y. (2024). Combined KRAS and TP53 Mutation in Patients with Colorectal Cancer Enhance Chemoresistance to Promote Postoperative Recurrence and Metastasis. BMC Cancer, 24.","DOI":"10.1186\/s12885-024-12776-8"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Pandey, H., Tang, D.W.T., Wong, S.H., and Lal, D. (2023). Gut Microbiota in Colorectal Cancer: Biological Role and Therapeutic Opportunities. Cancers, 15.","DOI":"10.3390\/cancers15030866"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s13578-019-0361-4","article-title":"Signaling Pathways Involved in Colorectal Cancer Progression","volume":"9","author":"Koveitypour","year":"2019","journal-title":"Cell Biosci."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Sawicki, T., Ruszkowska, M., Danielewicz, A., Nied\u017awiedzka, E., Ar\u0142ukowicz, T., and Przyby\u0142owicz, K.E. (2021). A Review of Colorectal Cancer in Terms of Epidemiology, Risk Factors, Development, Symptoms and Diagnosis. Cancers, 13.","DOI":"10.3390\/cancers13092025"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Roshandel, G., Ghasemi-Kebria, F., and Malekzadeh, R. (2024). Colorectal Cancer: Epidemiology, Risk Factors, and Prevention. Cancers, 16.","DOI":"10.3390\/cancers16081530"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1158\/2767-9764.CRC-23-0512","article-title":"Cumulative Incidence, Risk Factors, and Overall Survival of Disease Recurrence after Curative Resection of Stage II\u2013III Colorectal Cancer: A Population-Based Study","volume":"4","author":"Boute","year":"2024","journal-title":"Cancer Res. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.1007\/s00384-021-03914-w","article-title":"Disease Recurrence after Colorectal Cancer Surgery in the Modern Era: A Population-Based Study","volume":"36","author":"Qaderi","year":"2021","journal-title":"Int. J. Color. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Wu, Y., Li, Y., Xiong, X., Liu, X., Lin, B., and Xu, B. (2023). Recent Advances of Pathomics in Colorectal Cancer Diagnosis and Prognosis. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1094869"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1186\/s13046-021-02130-2","article-title":"Resistance to Anti-EGFR Therapies in Metastatic Colorectal Cancer: Underlying Mechanisms and Reversal Strategies","volume":"40","author":"Zhou","year":"2021","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Underwood, P.W., Ruff, S.M., and Pawlik, T.M. (2024). Update on Targeted Therapy and Immunotherapy for Metastatic Colorectal Cancer. Cells, 13.","DOI":"10.3390\/cells13030245"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1186\/s12935-022-02806-5","article-title":"Natural Essential Oils as a New Therapeutic Tool in Colorectal Cancer","volume":"22","author":"Garzoli","year":"2022","journal-title":"Cancer Cell Int."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Spisni, E., Petrocelli, G., Imbesi, V., Spigarelli, R., Azzinnari, D., Donati Sarti, M., Campieri, M., and Valerii, M.C. (2020). Antioxidant, Anti-Inflammatory, and Microbial-Modulating Activities of Essential Oils: Implications in Colonic Pathophysiology. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21114152"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"154106","DOI":"10.1155\/2014\/154106","article-title":"Essential Oils and Their Constituents as Anticancer Agents: A Mechanistic View","volume":"2014","author":"Gautam","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Petrocelli, G., Farabegoli, F., Valerii, M.C., Giovannini, C., Sardo, A., and Spisni, E. (2021). Molecules Present in Plant Essential Oils for Prevention and Treatment of Colorectal Cancer (CRC). Molecules, 26.","DOI":"10.3390\/molecules26040885"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10565-005-0085-6","article-title":"The Caco-2 Cell Line as a Model of the Intestinal Barrier: Influence of Cell and Culture-Related Factors on Caco-2 Cell Functional Characteristics","volume":"21","author":"Sambuy","year":"2005","journal-title":"Cell Biol. Toxicol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1248\/bpb.23.420","article-title":"Activation of NF-.KAPPA.B Determines the Sensitivity of Human Colon Cancer Cells to TNF.ALPHA.-Induced Apoptosis","volume":"23","author":"Han","year":"2000","journal-title":"Biol. Pharm. Bull."},{"key":"ref_19","first-page":"341","article-title":"Sandra Gessani 3D (Three-Dimensional) Caco-2 Spheroids: Optimized in Vitro Protocols to Favor Their Differentiation Process and to Analyze Their Cell Growth Behavior","volume":"4","author":"Rainaldi","year":"2016","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1186\/s12935-021-01853-8","article-title":"Challenges of Applying Multicellular Tumor Spheroids in Preclinical Phase","volume":"21","author":"Han","year":"2021","journal-title":"Cancer Cell Int."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1042\/CBI20100118","article-title":"Apoptotic Effect of Eugenol in Human Colon Cancer Cell Lines","volume":"35","author":"Jaganathan","year":"2011","journal-title":"Cell Biol. Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1039\/b300574g","article-title":"Evaluation of a Reversed-Phase Column (Supelcosil LC-ABZ) under Isocratic and Gradient Elution Conditions for Estimating Octanol\u2013Water Partition Coefficients","volume":"128","author":"Dias","year":"2003","journal-title":"Analyst"},{"key":"ref_23","unstructured":"Hansch, C., Leo, A., and Hoekman, D. (1995). Exploring QSAR\u2014Hydrophobic, Electronic, and Steric Constants, American Chemical Society."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1515\/znc-2002-11-1206","article-title":"Chemical Composition of Volatile Oil from Cinnamomum Zeylanicum Buds","volume":"57","author":"Jayaprakasha","year":"2002","journal-title":"Z. Naturforschung C"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4022","DOI":"10.1158\/0008-5472.CAN-07-6874","article-title":"Crucial Role of Interleukin-4 in the Survival of Colon Cancer Stem Cells","volume":"68","author":"Francipane","year":"2008","journal-title":"Cancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Bazzichetto, C., Milella, M., Zampiva, I., Simionato, F., Amoreo, C.A., Buglioni, S., Pacelli, C., Le Pera, L., Colombo, T., and Bria, E. (2022). Interleukin-8 in Colorectal Cancer: A Systematic Review and Meta-Analysis of Its Potential Role as a Prognostic Biomarker. Biomedicines, 10.","DOI":"10.3390\/biomedicines10102631"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1158\/1541-7786.MCR-10-0210","article-title":"Cytokine Induction of Tumor Necrosis Factor Receptor 2 Is Mediated by STAT3 in Colon Cancer Cells","volume":"9","author":"Hamilton","year":"2011","journal-title":"Mol. Cancer Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1038\/s41401-020-0359-9","article-title":"Cinnamaldehyde Protects against Rat Intestinal Ischemia\/Reperfusion Injuries by Synergistic Inhibition of NF-\u03baB and P53","volume":"41","author":"Almoiliqy","year":"2020","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1124\/jpet.119.262907","article-title":"Cinnamaldehyde Inhibits Inflammation of Human Synoviocyte Cells Through Regulation of Jak\/Stat Pathway and Ameliorates Collagen-Induced Arthritis in Rats","volume":"373","author":"Cheng","year":"2020","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Al-Harbi, S., Alkholiwy, E.M.A., Ali Ahmed, S.O., Aljurf, M., Al-Hejailan, R., and Aboussekhra, A. (2025). Eugenol Promotes Apoptosis in Leukemia Cells via Targeting the Mitochondrial Biogenesis PPRC1 Gene. Cells, 14.","DOI":"10.3390\/cells14040260"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Bezerra, D., Milit\u00e3o, G., De Morais, M., and De Sousa, D. (2017). The Dual Antioxidant\/Prooxidant Effect of Eugenol and Its Action in Cancer Development and Treatment. Nutrients, 9.","DOI":"10.3390\/nu9121367"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"107","DOI":"10.3892\/etm.2020.9539","article-title":"Eugenol Protects Cells against Oxidative Stress via Nrf2","volume":"21","author":"Ma","year":"2020","journal-title":"Exp. Ther. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1002\/hep.23848","article-title":"The Oncogenic Effect of Sulfatase 2 in Human Hepatocellular Carcinoma Is Mediated in Part by Glypican 3-Dependent Wnt Activation","volume":"52","author":"Lai","year":"2010","journal-title":"Hepatology"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Wang, C., Shang, C., Gai, X., Song, T., Han, S., Liu, Q., and Zheng, X. (2021). Sulfatase 2-Induced Cancer-Associated Fibroblasts Promote Hepatocellular Carcinoma Progression via Inhibition of Apoptosis and Induction of Epithelial-to-Mesenchymal Transition. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.631931"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"7026","DOI":"10.7150\/jca.62281","article-title":"uPAR: An Essential Factor for Tumor Development","volume":"12","author":"Lv","year":"2021","journal-title":"J. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/nrm2821","article-title":"Regulation of Cell Signalling by uPAR","volume":"11","author":"Smith","year":"2010","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Boulding, T., Wu, F., McCuaig, R., Dunn, J., Sutton, C.R., Hardy, K., Tu, W., Bullman, A., Yip, D., and Dahlstrom, J.E. (2016). Differential Roles for DUSP Family Members in Epithelial-to-Mesenchymal Transition and Cancer Stem Cell Regulation in Breast Cancer. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0148065"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Xu, Z., Zhang, Y., Dai, H., and Han, B. (2022). Epithelial\u2013Mesenchymal Transition-Mediated Tumor Therapeutic Resistance. Molecules, 27.","DOI":"10.3390\/molecules27154750"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Gao, X., Zhou, J., Qiao, Y., Lin, C., Zhang, G., Wu, Q., Su, Z., Zhang, Q., and Huang, S. (2025). ATP6V0A4 as a Novel Prognostic Biomarker and Potential Therapeutic Target in Oral Squamous Cell Carcinoma. BMC Oral Health, 25.","DOI":"10.1186\/s12903-025-06653-4"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"13626","DOI":"10.1038\/s41598-021-92720-z","article-title":"High Expression of DNA Damage-Inducible Transcript 4 (DDIT4) Is Associated with Advanced Pathological Features in the Patients with Colorectal Cancer","volume":"11","author":"Fattahi","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1186\/s12935-021-02002-x","article-title":"Overexpression of DDIT4 and TPTEP1 Are Associated with Metastasis and Advanced Stages in Colorectal Cancer Patients: A Study Utilizing Bioinformatics Prediction and Experimental Validation","volume":"21","author":"Fattahi","year":"2021","journal-title":"Cancer Cell Int."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"215","DOI":"10.15283\/ijsc22188","article-title":"Alterations and Co-Occurrence of C-MYC, N-MYC, and L-MYC Expression Are Related to Clinical Outcomes in Various Cancers","volume":"16","author":"Lee","year":"2023","journal-title":"Int. J. Stem Cells"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1158\/2159-8290.CD-15-0507","article-title":"MYC, Metabolism, and Cancer","volume":"5","author":"Stine","year":"2015","journal-title":"Cancer Discov."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"11","DOI":"10.3892\/or.2023.8670","article-title":"RPF2 Mediates the CARM1-MYCN Axis to Promote Chemotherapy Resistance in Colorectal Cancer Cells","volume":"51","author":"Lu","year":"2023","journal-title":"Oncol. Rep."},{"key":"ref_45","first-page":"125","article-title":"Aggressive Subtypes of Human Colorectal Tumors Frequently Exhibit Amplification of the C-Myc Gene","volume":"6","author":"Heerdt","year":"1991","journal-title":"Oncogene"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"216693","DOI":"10.1016\/j.canlet.2024.216693","article-title":"NR4A1 Depletion Inhibits Colorectal Cancer Progression by Promoting Necroptosis via the RIG-I-like Receptor Pathway","volume":"585","author":"Zhu","year":"2024","journal-title":"Cancer Lett."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Li, M., Zhang, Z., Li, M., Chen, Z., Tang, W., and Cheng, X. (2023). NR4A1 as a Potential Therapeutic Target in Colon Adenocarcinoma: A Computational Analysis of Immune Infiltration and Drug Response. Front. Genet., 14.","DOI":"10.3389\/fgene.2023.1181320"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e399","DOI":"10.1038\/emm.2017.184","article-title":"Therapeutic Inhibition of SGK1 Suppresses Colorectal Cancer","volume":"49","author":"Liang","year":"2017","journal-title":"Exp. Mol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Sang, Y., Kong, P., Zhang, S., Zhang, L., Cao, Y., Duan, X., Sun, T., Tao, Z., and Liu, W. (2021). SGK1 in Human Cancer: Emerging Roles and Mechanisms. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.608722"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/s41586-019-0979-8","article-title":"Genome-Wide Analysis Identifies NR4A1 as a Key Mediator of T Cell Dysfunction","volume":"567","author":"Liu","year":"2019","journal-title":"Nature"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"120899","DOI":"10.1016\/j.lfs.2022.120899","article-title":"Tumor-Mediated 4-1BB Induces Tumor Proliferation and Metastasis in the Colorectal Cancer Cells","volume":"307","author":"Kim","year":"2022","journal-title":"Life Sci."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Weaver, A.N., and Yang, E.S. (2013). Beyond DNA Repair: Additional Functions of PARP-1 in Cancer. Front. Oncol., 3.","DOI":"10.3389\/fonc.2013.00290"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.cell.2016.03.014","article-title":"On the Dependency of Cellular Protein Levels on mRNA Abundance","volume":"165","author":"Liu","year":"2016","journal-title":"Cell"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Pfeffer, C., and Singh, A. (2018). Apoptosis: A Target for Anticancer Therapy. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19020448"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1007\/s12672-024-01112-y","article-title":"PARP1 Bound to XRCC2 Promotes Tumor Progression in Colorectal Cancer","volume":"15","author":"Xu","year":"2024","journal-title":"Discov. Onc."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Demuth, P., Thibol, L., Lemsch, A., Potlitz, F., Schulig, L., Grathwol, C., Manolikakes, G., Schade, D., Roukos, V., and Link, A. (2024). Targeting PARP-1 and DNA Damage Response Defects in Colorectal Cancer Chemotherapy with Established and Novel PARP Inhibitors. Cancers, 16.","DOI":"10.3390\/cancers16203441"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Ravizza, R., Gariboldi, M.B., Passarelli, L., and Monti, E. (2004). Role of the P53\/P21 System in the Response of Human Colon Carcinoma Cells to Doxorubicin. BMC Cancer, 4.","DOI":"10.1186\/1471-2407-4-92"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Shamloo, B., and Usluer, S. (2019). P21 in Cancer Research. Cancers, 11.","DOI":"10.3390\/cancers11081178"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/s41420-025-02416-w","article-title":"Dual Role of P21 in Regulating Apoptosis and Mitotic Integrity in Response to Doxorubicin in Colon Cancer Cells","volume":"11","author":"Kim","year":"2025","journal-title":"Cell Death Discov."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"15540","DOI":"10.1074\/jbc.273.25.15540","article-title":"Caspase-3 Is Required for \u03b1-Fodrin Cleavage but Dispensable for Cleavage of Other Death Substrates in Apoptosis","volume":"273","author":"Ng","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_61","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_62","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1002\/ijc.31374","article-title":"Caspase-3 Regulates the Migration, Invasion and Metastasis of Colon Cancer Cells","volume":"143","author":"Zhou","year":"2018","journal-title":"Int. J. Cancer"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1093\/carcin\/bgw041","article-title":"Can Supplementation of Phytoestrogens\/Insoluble Fibers Help the Management of Duodenal Polyps in Familial Adenomatous Polyposis?","volume":"37","author":"Calabrese","year":"2016","journal-title":"CARCIN"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1038\/sj.bjc.6603094","article-title":"RNA Interference as a Key to Knockdown Overexpressed Cyclooxygenase-2 Gene in Tumour Cells","volume":"94","author":"Strillacci","year":"2006","journal-title":"Br. J. Cancer"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1038\/nprot.2006.339","article-title":"Clonogenic Assay of Cells in Vitro","volume":"1","author":"Franken","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Spigarelli, R., Calabrese, C., Spisni, E., Vinciguerra, S., Saracino, I.M., Dussias, N.K., Filippone, E., and Valerii, M.C. (2024). Palmitoylethanolamide (PEA) for Prevention of Gastroesophageal Inflammation: Insights from In Vitro Models. Life, 14.","DOI":"10.3390\/life14101221"},{"key":"ref_67","unstructured":"(2024, October 27). FastQC A Quality Control Tool for High Throughput Sequence Data. Available online: https:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc\/."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"10","DOI":"10.14806\/ej.17.1.200","article-title":"Cutadapt Removes Adapter Sequences from High-Throughput Sequencing Reads","volume":"17","author":"Martin","year":"2011","journal-title":"EMBnet J."},{"key":"ref_69","unstructured":"(2024, October 27). GENCODE. Available online: https:\/\/www.gencodegenes.org\/."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast Universal RNA-Seq Aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"gkv711","DOI":"10.1093\/nar\/gkv711","article-title":"Data Quality Aware Analysis of Differential Expression in RNA-Seq with NOISeq R\/Bioc Package","volume":"43","author":"Tarazona","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: An R Package for Comparing Biological Themes Among Gene Clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS A J. Integr. Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","article-title":"The Molecular Signatures Database Hallmark Gene Set Collection","volume":"1","author":"Liberzon","year":"2015","journal-title":"Cell Syst."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/2\/649\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T09:13:50Z","timestamp":1768209230000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/2\/649"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,8]]},"references-count":73,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["ijms27020649"],"URL":"https:\/\/doi.org\/10.3390\/ijms27020649","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,8]]}}}