{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:26:31Z","timestamp":1790162791203,"version":"4.1.0"},"reference-count":60,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Florida Cancer Innovation Fund from the Department of Health, Florida"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Triple-negative breast cancer (TNBC) remains highly aggressive and refractory to conventional treatments, underscoring the need for novel combination strategies. Here, we employed 2D and 3D in vitro models, transcriptomic profiling, and in vivo xenograft studies to evaluate the anticancer efficacy of cannabinoids combined with the terpene \u03b2-caryophyllene (BC) in resistant TNBC models. Among the tested cannabinoids, cannabichromene (CBC) exhibited the greatest potency, and its combination with BC at sub-toxic concentrations significantly reduced IC50 values, enhanced cytotoxicity in spheroids, and suppressed colony formation and migration. The combination treatment induced pronounced G1 cell cycle arrest and increased apoptotic cell death. Western blot analyses revealed downregulation of PARP, Survivin, mTOR, Vimentin, Glypican-5, and PD-L1, while RNA sequencing demonstrated suppression of proliferative and migratory signaling pathways alongside activation of apoptosis, autophagy, and ferroptosis-related pathways. In vivo, CBC + BC significantly inhibited tumor growth in MDA-MB-231 xenografts, outperforming single-agent treatments. Collectively, these findings demonstrate that BC synergistically enhances cannabinoid activity, yielding superior antiproliferative and anti-migratory effects, and highlight this combination as a promising therapeutic strategy for resistant TNBC.<\/jats:p>","DOI":"10.3390\/ijms27062730","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T14:03:27Z","timestamp":1773756207000},"page":"2730","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Synergistic Anticancer Activity of Cannabinoids and Terpenes Against Triple-Negative Breast Cancer Resistance"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7809-4682","authenticated-orcid":false,"given":"Mounika","family":"Aare","sequence":"first","affiliation":[{"name":"College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jassy Mary","family":"Lazarte","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1852-6548","authenticated-orcid":false,"given":"Aakash","family":"Nathani","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Breana","family":"Boirie","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamiel N.","family":"Turley","sequence":"additional","affiliation":[{"name":"Cancer Biology Department, Mayo Clinic, Jacksonville, FL 32224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"John A.","family":"Copland","sequence":"additional","affiliation":[{"name":"Cancer Biology Department, Mayo Clinic, Jacksonville, FL 32224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9192-8143","authenticated-orcid":false,"given":"Mandip","family":"Singh","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,17]]},"reference":[{"key":"ref_1","first-page":"141","article-title":"Drug Resistance and Combating Drug Resistance in Cancer","volume":"2","author":"Wang","year":"2019","journal-title":"Cancer Drug Resist."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4215","DOI":"10.21873\/anticanres.15226","article-title":"Telmisartan Facilitates the Anticancer Effects of CARP-1 Functional Mimetic and Sorafenib in Rociletinib Resistant Non-Small Cell Lung Cancer","volume":"41","author":"Surapaneni","year":"2021","journal-title":"Anticancer Res."},{"key":"ref_3","first-page":"e171","article-title":"Pharmacokinetic, Biodistribution and Therapeutic Efficacy of 5-Fluorouracil-Loaded pH-Sensitive PEGylated Liposomal Nanoparticles in HCT-116 Tumor Bearing Mouse","volume":"2","author":"Udofot","year":"2016","journal-title":"J. Nat. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1021\/acs.molpharmaceut.6b00187","article-title":"Combination Approach of YSA Peptide Anchored Docetaxel Stealth Liposomes with Oral Antifibrotic Agent for the Treatment of Lung Cancer","volume":"13","author":"Patel","year":"2016","journal-title":"Mol. Pharm."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/s41586-019-1730-1","article-title":"A View on Drug Resistance in Cancer","volume":"575","author":"Vasan","year":"2019","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s12935-015-0221-1","article-title":"Resistance to Cancer Chemotherapy: Failure in Drug Response from ADME to P-Gp","volume":"15","author":"Alfarouk","year":"2015","journal-title":"Cancer Cell Int."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Emran, T.B., Shahriar, A., Mahmud, A.R., Rahman, T., Abir, M.H., Siddiquee, M.F.-R., Ahmed, H., Rahman, N., Nainu, F., and Wahyudin, E. (2022). Multidrug Resistance in Cancer: Understanding Molecular Mechanisms, Immunoprevention and Therapeutic Approaches. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.891652"},{"key":"ref_8","first-page":"1267","article-title":"The Pharmacology of Cancer Resistance","volume":"27","year":"2007","journal-title":"Anticancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s13148-018-0587-8","article-title":"The Role and Mechanisms of Action of microRNAs in Cancer Drug Resistance","volume":"11","author":"Si","year":"2019","journal-title":"Clin. Epigenet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.1002\/(SICI)1097-0142(20000501)88:9<1986::AID-CNCR2>3.0.CO;2-I","article-title":"Combined Therapy Consisting of Intraarterial Cisplatin Infusion and Systemic Interferon-\u03b1 for Hepatocellular Carcinoma Patients with Major Portal Vein Thrombosis or Distant Metastasis","volume":"88","author":"Chung","year":"2000","journal-title":"Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.canlet.2007.09.015","article-title":"Enhanced Anti-Tumor Effect of Combination Therapy with Gemcitabine and Apigenin in Pancreatic Cancer","volume":"259","author":"Lee","year":"2008","journal-title":"Cancer Lett."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Suraweera, A., O\u2019Byrne, K.J., and Richard, D.J. (2018). Combination Therapy with Histone Deacetylase Inhibitors (HDACi) for the Treatment of Cancer: Achieving the Full Therapeutic Potential of HDACi. Front. Oncol., 8.","DOI":"10.3389\/fonc.2018.00092"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"100069","DOI":"10.1016\/j.amolm.2025.100069","article-title":"Novel Combination Therapy of Osimertinib and Tupichinol E in Triple-Negative Breast Cancer: Targeting EGFR and CDK4\/6 Pathways","volume":"5","author":"Samantaray","year":"2025","journal-title":"Asp. Mol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0014-2999(98)00392-6","article-title":"An Entourage Effect: Inactive Endogenous Fatty Acid Glycerol Esters Enhance 2-Arachidonoyl-Glycerol Cannabinoid Activity","volume":"353","author":"Fride","year":"1998","journal-title":"Eur. J. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Russo, E.B. (2019). The Case for the Entourage Effect and Conventional Breeding of Clinical Cannabis: No \u201cStrain,\u201d No Gain. Front. Plant Sci., 9.","DOI":"10.3389\/fpls.2018.01969"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Pertwee, R.G. (2014). Handbook of Cannabis, Oxford University Press.","DOI":"10.1093\/acprof:oso\/9780199662685.001.0001"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1158\/0008-5472.CAN-07-2785","article-title":"Cannabinoids for Cancer Treatment: Progress and Promise","volume":"68","author":"Sarfaraz","year":"2008","journal-title":"Cancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1093\/jnci\/55.3.597","article-title":"Antineoplastic Activity of Cannabinoids2","volume":"55","author":"Munson","year":"1975","journal-title":"JNCI J. Natl. Cancer Inst."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2633","DOI":"10.1096\/fj.06-6638fje","article-title":"Cannabinoid Receptors as Novel Targets for the Treatment of Melanoma","volume":"20","author":"Carracedo","year":"2006","journal-title":"FASEB J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6748","DOI":"10.1158\/0008-5472.CAN-06-0169","article-title":"Cannabinoids Induce Apoptosis of Pancreatic Tumor Cells via Endoplasmic Reticulum Stress-Related Genes","volume":"66","author":"Carracedo","year":"2006","journal-title":"Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1038\/sj.onc.1210641","article-title":"Delta9-Tetrahydrocannabinol Inhibits Epithelial Growth Factor-Induced Lung Cancer Cell Migration in Vitro as Well as Its Growth and Metastasis In Vivo","volume":"27","author":"Preet","year":"2008","journal-title":"Oncogene"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/sj.bjc.6603236","article-title":"A Pilot Clinical Study of \u03949-Tetrahydrocannabinol in Patients with Recurrent Glioblastoma Multiforme","volume":"95","author":"Duarte","year":"2006","journal-title":"Br. J. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1007\/s00018-006-6156-x","article-title":"The Non-Psychoactive Cannabidiol Triggers Caspase Activation and Oxidative Stress in Human Glioma Cells","volume":"63","author":"Massi","year":"2006","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Walsh, K.B., McKinney, A.E., and Holmes, A.E. (2021). Minor Cannabinoids: Biosynthesis, Molecular Pharmacology and Potential Therapeutic Uses. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.777804"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.2174\/1871520620666200227093216","article-title":"Beta-Caryophyllene Suppresses Ovarian Cancer Proliferation by Inducing Cell Cycle Arrest and Apoptosis","volume":"20","author":"Arul","year":"2020","journal-title":"Anti-Cancer Agents Med. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Dahham, S.S., Tabana, Y., Asif, M., Ahmed, M., Babu, D., Hassan, L.E., Ahamed, M.B.K., Sandai, D., Barakat, K., and Siraki, A. (2021). \u03b2-Caryophyllene Induces Apoptosis and Inhibits Angiogenesis in Colorectal Cancer Models. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910550"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1211\/jpp.59.12.0005","article-title":"Potentiating Effect of \u03b2-Caryophyllene on Anticancer Activity of \u03b1-Humulene, Isocaryophyllene and Paclitaxel","volume":"59","author":"Legault","year":"2007","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Di Sotto, A., Irannejad, H., Eufemi, M., Mancinelli, R., Abete, L., Mammola, C.L., Altieri, F., Mazzanti, G., and Di Giacomo, S. (2020). Potentiation of Low-Dose Doxorubicin Cytotoxicity by Affecting P-Glycoprotein through Caryophyllane Sesquiterpenes in HepG2 Cells: An in vitro and in silico study. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21020633"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Mannino, F., Pallio, G., Corsaro, R., Minutoli, L., Altavilla, D., Vermiglio, G., Allegra, A., Eid, A.H., Bitto, A., and Squadrito, F. (2021). Beta-Caryophyllene Exhibits Anti-Proliferative Effects through Apoptosis Induction and Cell Cycle Modulation in Multiple Myeloma Cells. Cancers, 13, Erratum in Cancers\u00a02023, 15, 5250. https:\/\/doi.org\/10.3390\/cancers15215250.","DOI":"10.3390\/cancers15215250"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.canlet.2011.08.001","article-title":"\u03b2-Caryophyllene Oxide Inhibits Growth and Induces Apoptosis through the Suppression of PI3K\/AKT\/mTOR\/S6K1 Pathways and ROS-Mediated MAPKs Activation","volume":"312","author":"Park","year":"2011","journal-title":"Cancer Lett."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.21873\/anticanres.11433","article-title":"Chemosensitizing Properties of \u03b2-Caryophyllene and \u03b2-Caryophyllene Oxide in Combination with Doxorubicin in Human Cancer Cells","volume":"37","author":"Mazzanti","year":"2017","journal-title":"Anticancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ahmed, E.A., Abu Zahra, H., Ammar, R.B., Mohamed, M.E., and Ibrahim, H.-I.M. (2022). Beta-Caryophyllene Enhances the Anti-Tumor Activity of Cisplatin in Lung Cancer Cell Lines through Regulating Cell Cycle and Apoptosis Signaling Molecules. Molecules, 27.","DOI":"10.3390\/molecules27238354"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Tomko, A.M., Whynot, E.G., Ellis, L.D., and Dupr\u00e9, D.J. (2020). Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis. Cancers, 12.","DOI":"10.3390\/cancers12071985"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.jtcme.2024.04.007","article-title":"Cannabidiol Suppresses Proliferation and Induces Cell Death, Autophagy and Senescence in Human Cholangiocarcinoma Cells via the PI3K\/AKT\/mTOR Pathway","volume":"14","author":"Pongking","year":"2024","journal-title":"J. Tradit. Complement. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4307","DOI":"10.1038\/s41598-025-88917-1","article-title":"Cannabidiol Attenuates Lipid Metabolism and Induces CB1 Receptor-Mediated ER Stress Associated Apoptosis in Ovarian Cancer Cells","volume":"15","author":"Fu","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Zhang, X., Qin, Y., Pan, Z., Li, M., Liu, X., Chen, X., Qu, G., Zhou, L., Xu, M., and Zheng, Q. (2019). Cannabidiol Induces Cell Cycle Arrest and Cell Apoptosis in Human Gastric Cancer SGC-7901 Cells. Biomolecules, 9.","DOI":"10.3390\/biom9080302"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/s12032-025-02790-6","article-title":"Targeting Gastrointestinal Cancers with Cannabidiol: Mechanisms, Challenges, and Therapeutic Implications","volume":"42","author":"Esmaeli","year":"2025","journal-title":"Med. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.taap.2007.09.012","article-title":"Cannabidiol-Induced Apoptosis in Primary Lymphocytes Is Associated with Oxidative Stress-Dependent Activation of Caspase-8","volume":"226","author":"Wu","year":"2008","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/s00068-025-02767-0","article-title":"Cannabidiol Protects Lung against Inflammation and Apoptosis in a Rat Model of Blunt Chest Trauma via Bax\/Bcl-2\/Cas-9 Signaling Pathway","volume":"51","author":"Emre","year":"2025","journal-title":"Eur. J. Trauma. Emerg. Surg."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.biochi.2008.11.003","article-title":"Apoptosis Induced in HepG2 Cells by the Synthetic Cannabinoid WIN: Involvement of the Transcription Factor PPAR\u03b3","volume":"91","author":"Giuliano","year":"2009","journal-title":"Biochimie"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Peeri, H., and Koltai, H. (2022). Cannabis Biomolecule Effects on Cancer Cells and Cancer Stem Cells: Cytotoxic, Anti-Proliferative, and Anti-Migratory Activities. Biomolecules, 12.","DOI":"10.3390\/biom12040491"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Wittig, F., Koch, F., Pannenberg, L., Bekeschus, S., Ramer, R., and Hinz, B. (2024). \u03b2-Caryophyllene Inhibits Endothelial Tube Formation by Modulating the Secretome of Hypoxic Lung Cancer Cells\u2014Possible Role of VEGF Downregulation. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25020810"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Ahmed, E.A. (2025). The Potential Therapeutic Role of Beta-Caryophyllene as a Chemosensitizer and an Inhibitor of Angiogenesis in Cancer. Molecules, 30.","DOI":"10.3390\/molecules30081751"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Basheer, I., Wang, H., Li, G., Jehan, S., Raza, A., Du, C., Ullah, N., Li, D., and Sui, G. (2024). \u03b2-Caryophyllene Sensitizes Hepatocellular Carcinoma Cells to Chemotherapeutics and Inhibits Cell Malignancy through Targeting MAPK Signaling Pathway. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1492670"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"110995","DOI":"10.1016\/j.cbi.2024.110995","article-title":"Cannabidiol Induces ERK Activation and ROS Production to Promote Autophagy and Ferroptosis in Glioblastoma Cells","volume":"394","author":"Kim","year":"2024","journal-title":"Chem. Biol. Interact."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"116363","DOI":"10.1016\/j.biopha.2024.116363","article-title":"Emerging Trends of Phytochemicals as Ferroptosis Modulators in Cancer Therapy","volume":"173","author":"Khan","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Xiu, Z., Zhu, Y., Han, J., Li, Y., Yang, X., Yang, G., Song, G., Li, S., Li, Y., and Cheng, C. (2022). Caryophyllene Oxide Induces Ferritinophagy by Regulating the NCOA4\/FTH1\/LC3 Pathway in Hepatocellular Carcinoma. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.930958"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Wu, Y.-T., Zhong, L.-S., Huang, C., Guo, Y.-Y., Jin, F.-J., Hu, Y.-Z., Zhao, Z.-B., Ren, Z., and Wang, Y.-F. (2022). \u03b2-Caryophyllene Acts as a Ferroptosis Inhibitor to Ameliorate Experimental Colitis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232416055"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e94","DOI":"10.1089\/can.2023.0212","article-title":"Activation of CB2 Receptors by (\u2212)-Cannabichromene but Not (+)-Cannabichromene","volume":"10","author":"Udoh","year":"2025","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"108022","DOI":"10.1016\/j.phrs.2025.108022","article-title":"The Development and Therapeutic Potential of Classical and Next-Generation Cannabinoid Ligands","volume":"222","year":"2025","journal-title":"Pharmacol. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/s41417-020-0182-y","article-title":"Interplay between MTOR and GPX4 Signaling Modulates Autophagy-Dependent Ferroptotic Cancer Cell Death","volume":"28","author":"Liu","year":"2021","journal-title":"Cancer Gene Ther."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.biochi.2022.12.008","article-title":"The Role of Cannabidiol and Tetrahydrocannabivarin to Overcome Doxorubicin Resistance in MDA-MB-231 Xenografts in Athymic Nude Mice","volume":"208","author":"Kalvala","year":"2023","journal-title":"Biochimie"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s13105-018-0611-7","article-title":"Cannabinoid-Induced Cell Death in Endometrial Cancer Cells: Involvement of TRPV1 Receptors in Apoptosis","volume":"74","author":"Fonseca","year":"2018","journal-title":"J. Physiol. Biochem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1177\/2472630319854337","article-title":"Automating a Magnetic 3D Spheroid Model Technology for High-Throughput Screening","volume":"24","author":"Baillargeon","year":"2019","journal-title":"SLAS Technol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"020025","DOI":"10.1063\/1.5125529","article-title":"Establishment of Primary 3D Cell Culture Based on Magnetic Bioprinting for Colorectal Cancer Cells from Patients in Cipto Mangunkusumo National Hospital Indonesia","volume":"Volume 2155","author":"Abdullah","year":"2019","journal-title":"AIP Conference Proceedings"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Liu, X., He, M., Li, L., Wang, X., Han, S., Zhao, J., Dong, Y., Ahmad, M., Li, L., and Zhang, X. (2021). EMT and Cancer Cell Stemness Associated with Chemotherapeutic Resistance in Esophageal Cancer. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.672222"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"120943","DOI":"10.1016\/j.ijpharm.2021.120943","article-title":"Cannabidiol Loaded Extracellular Vesicles Sensitize Triple-Negative Breast Cancer to Doxorubicin in Both in-Vitro and in Vivo Models","volume":"607","author":"Patel","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_58","first-page":"301","article-title":"Acridine Orange\/Ethidium Bromide Double Staining Test: A Simple In-Vitro Assay to Detect Apoptosis Induced by Phenolic Compounds in Plant Cells","volume":"26","author":"Ciniglia","year":"2010","journal-title":"Allelopath. J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.3892\/or.2013.2942","article-title":"Differential Effects of Erufosine on Proliferation, Wound Healing and Apoptosis in Colorectal Cancer Cell Lines","volume":"31","author":"Berger","year":"2014","journal-title":"Oncol. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"105290","DOI":"10.1016\/j.bioorg.2021.105290","article-title":"Anticancer Effect Evaluation in Vitro and in Vivo of Iridium(III) Polypyridyl Complexes Targeting DNA and Mitochondria","volume":"115","author":"Zhang","year":"2021","journal-title":"Bioorganic Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/6\/2730\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T14:03:39Z","timestamp":1773756219000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/6\/2730"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,17]]},"references-count":60,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["ijms27062730"],"URL":"https:\/\/doi.org\/10.3390\/ijms27062730","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,17]]}}}