{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:56:11Z","timestamp":1790178971175,"version":"4.1.0"},"reference-count":60,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,4,21]],"date-time":"2020-04-21T00:00:00Z","timestamp":1587427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Background: As part of the efforts to find natural alternatives for cancer treatment and to overcome the barriers of cellular resistance to chemotherapeutic agents, polymeric nanocapsules containing curcumin and\/or methotrexate were prepared by an interfacial deposition of preformed polymer method. Methods: Physicochemical properties, drug release experiments and in vitro cytotoxicity of these nanocapsules were performed against the Calu-3 lung cancer cell line. Results: The colloidal suspensions of nanocapsules showed suitable size (287 to 325 nm), negative charge (\u221233 to \u221241 mV) and high encapsulation efficiency (82.4 to 99.4%). Spherical particles at nanoscale dimensions were observed by scanning electron microscopy. X-ray diffraction analysis indicated that nanocapsules exhibited a non-crystalline pattern with a remarkable decrease of crystalline peaks of the raw materials. Fourier-transform infrared spectra demonstrated no chemical bond between the drug(s) and polymers. Drug release experiments evidenced a controlled release pattern with no burst effect for nanocapsules containing curcumin and\/or methotrexate. The nanoformulation containing curcumin and methotrexate (NCUR\/MTX-2) statistically decreased the cell viability of Calu-3. The fluorescence and morphological analyses presented a predominance of early apoptosis and late apoptosis as the main death mechanisms for Calu-3. Conclusions: Curcumin and methotrexate co-loaded nanocapsules can be further used as a novel therapeutic strategy for treating non-small-cell lung cancer.<\/jats:p>","DOI":"10.3390\/molecules25081913","type":"journal-article","created":{"date-parts":[[2020,4,21]],"date-time":"2020-04-21T05:48:52Z","timestamp":1587448132000},"page":"1913","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Co-Loaded Curcumin and Methotrexate Nanocapsules Enhance Cytotoxicity against Non-Small-Cell Lung Cancer Cells"],"prefix":"10.3390","volume":"25","author":[{"given":"Loanda Aparecida Cabral","family":"Rudnik","sequence":"first","affiliation":[{"name":"Postgraduate Program in Pharmaceutical Sciences, Department of Pharmaceutical Sciences, State University of Ponta Grossa, 84030-900 Ponta Grossa, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo Vitor","family":"Farago","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Pharmaceutical Sciences, Department of Pharmaceutical Sciences, State University of Ponta Grossa, 84030-900 Ponta Grossa, Brazil"},{"name":"Postgraduate Program in Pharmaceutical Sciences, Department of Pharmacy, Federal University of Paran\u00e1, 81020-430 Curitiba, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1873-2253","authenticated-orcid":false,"given":"Jane","family":"Manfron Budel","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Pharmaceutical Sciences, Department of Pharmaceutical Sciences, State University of Ponta Grossa, 84030-900 Ponta Grossa, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5849-669X","authenticated-orcid":false,"given":"Amanda","family":"Lyra","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Pharmaceutical Sciences, Department of Pharmaceutical Sciences, State University of Ponta Grossa, 84030-900 Ponta Grossa, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda Malaquias","family":"Barboza","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Pharmaceutical Sciences, Department of Pharmaceutical Sciences, State University of Ponta Grossa, 84030-900 Ponta Grossa, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Traudi","family":"Klein","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Pharmaceutical Sciences, Department of Pharmaceutical Sciences, State University of Ponta Grossa, 84030-900 Ponta Grossa, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla Cristine","family":"Kanunfre","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Biomedical Science, Department of General Biology, State University of Ponta Grossa, 84030-900 Ponta Grossa, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica Mendes","family":"Nadal","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Pharmaceutical Sciences, Department of Pharmaceutical Sciences, State University of Ponta Grossa, 84030-900 Ponta Grossa, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matheus Coelho","family":"Band\u00e9ca","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Dentistry, Ceuma University, 65065-470 S\u00e3o Lu\u00eds, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7368-9644","authenticated-orcid":false,"given":"Vijayasankar","family":"Raman","sequence":"additional","affiliation":[{"name":"National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, MS 38677, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andressa","family":"Novatski","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Pharmaceutical Sciences, Department of Pharmaceutical Sciences, State University of Ponta Grossa, 84030-900 Ponta Grossa, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro Dourado","family":"Logu\u00e9rcio","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Pharmaceutical Sciences, Department of Pharmaceutical Sciences, State University of Ponta Grossa, 84030-900 Ponta Grossa, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra Maria Warumby","family":"Zanin","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Pharmaceutical Sciences, Department of Pharmacy, Federal University of Paran\u00e1, 81020-430 Curitiba, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,21]]},"reference":[{"key":"ref_1","first-page":"38","article-title":"Targeted Drug Delivery Systems for Lung Cancer","volume":"3","author":"Waheed","year":"2015","journal-title":"PharmaTutor"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12943-018-0930-x","article-title":"Circular RNA 100146 functions as an oncogene through direct binding to miR361-3p and miR-615-5p in non-small cell lung cancer","volume":"18","author":"Chen","year":"2019","journal-title":"Mol. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2148","DOI":"10.1590\/S0100-40422010001000027","article-title":"Glicoprote\u00edna-p, resist\u00eancia a m\u00faltiplas drogas (mdr) e rela\u00e7\u00e3o estrutura-atividade de moduladores","volume":"33","author":"Huber","year":"2010","journal-title":"Quim. Nova"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.cej.2019.02.201","article-title":"A novel chitosan-based nanomedicine for multi-drug resistant breast cancer therapy","volume":"369","author":"Niu","year":"2019","journal-title":"Chem. Eng. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.neulet.2018.10.016","article-title":"Effects of carbamazepine on the P-gp and CYP3A expression correlated with PXR or NF-\u03baB activity in the bEnd.3 cells","volume":"690","author":"Ke","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.colsurfb.2018.11.077","article-title":"Rational design of polymer-lipid nanoparticles for docetaxel delivery","volume":"175","author":"Albano","year":"2019","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1016\/j.bcp.2004.07.009","article-title":"Biochemical mechanism of modulation of human P-glycoprotein (ABCB1) by curcumin I, II and III purified from Turmeric powder","volume":"68","author":"Chearwae","year":"2004","journal-title":"Biochem. Pharmacol."},{"key":"ref_8","first-page":"538","article-title":"Curcumina, o P\u00f3 Dourado do A\u00e7afr\u00e3o-Da-Terra: Introspec\u00e7\u00f5es Sobre Qu\u00edmica e Atividades Biol\u00f3gicas","volume":"38","author":"Santiago","year":"2015","journal-title":"Qu\u00edm. Nova"},{"key":"ref_9","first-page":"1","article-title":"Computational simulation of inhibitory effects of curcumin, retinoic acid and their conjugates on GSK-3 beta","volume":"8","author":"Mishra","year":"2019","journal-title":"New Model Anal. Health Inform. Bioinform"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1016\/j.ejca.2005.05.009","article-title":"Curcumin: The story so far","volume":"41","author":"Sharma","year":"2005","journal-title":"Eur. J. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.colsurfb.2016.11.036","article-title":"Nanoencapsulation, an efficient and promising approach to maximize wound healing efficacy of curcumin: A review of new trends and state-of-the-art","volume":"150","author":"Huaasin","year":"2017","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1021\/jf5042307","article-title":"Demethoxycurcumin Modulates Human P-Glycoprotein Function via Uncompetitive Inhibition of ATPase Hydrolysis Activity","volume":"63","author":"Teng","year":"2015","journal-title":"J. Agric. Food Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.colsurfb.2012.06.024","article-title":"Pharmacokinetics of curcumin-loaded PLGA and PLGA-PEG blend nanoparticles after oral administration in rats","volume":"101","author":"Khalil","year":"2013","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.colsurfb.2019.02.008","article-title":"Synthesis and colloidal characterization of folic acid-modified PEG-b-PCL Micelles for methotrexate delivery","volume":"177","author":"Brandt","year":"2019","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.colsurfb.2018.11.053","article-title":"Lipid and TPGS based novel core-shell type nanocapsular sustained release system of methotrexate for intravenous application","volume":"174","author":"Katiyar","year":"2019","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/S0378-4347(01)00402-9","article-title":"Separation methods for methotrexate, its structural analogues and metabolites","volume":"764","author":"Rubino","year":"2001","journal-title":"Chromatogr B"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.ijpharm.2006.09.058","article-title":"Effect of DC\/mDC iontophoresis and terpenes on transdermal permeation of methotrexate: In vitro study","volume":"333","author":"Prasad","year":"2007","journal-title":"Int. J. Pharm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1475-2867-5-30","article-title":"ABC transporters as multidrug resistance mechanisms and the development of chemosensitizers for their reversal","volume":"5","author":"Choi","year":"2005","journal-title":"Cancer Cell Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.ijpharm.2014.02.020","article-title":"Methotrexate-bestatin interaction: Involvement of P-glycoprotein and organic anion transporters in rats","volume":"465","author":"Zhu","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.carbpol.2015.09.016","article-title":"Alginate stabilized gold nanoparticle as multidrug Carrier: Evaluation of cellular interactions and hemolytic potential","volume":"136","author":"Dey","year":"2016","journal-title":"Carbohydr. Polym."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.colsurfb.2018.04.057","article-title":"Facile synthesis of pH-responsive polymersomes based on lipidized PEG for intracellular co-delivery of curcumin and methotrexate","volume":"1","author":"Curcio","year":"2018","journal-title":"Colloids Surf. B Biointerfaces."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.colsurfb.2019.110515","article-title":"Methotrexate and Curcumin co-encapsulated PLGA nanoparticles as a potential breast cancer therapeutic system: In vitro and In vivo evaluation","volume":"184","author":"Vakilinezhad","year":"2019","journal-title":"Colloids Surf. B Biointerfaces."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Curcio, M., Cirillo, G., Tucci, P., Farfalla, A., Bevacqua, E., Vittorio, O., Iemma, F., and Nicoletta, F.P. (2020). Dextran-Curcumin Nanoparticles as a Methotrexate Delivery Vehicle: A Step Forward in Breast Cancer Combination Therapy. Pharmaceuticals, 2.","DOI":"10.3390\/ph13010002"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.msec.2018.10.029","article-title":"Long-lasting anti-platelet activity of cilostazol from poly(\u03b5-caprolactone) poly(ethylene glycol) blend nanocapsules","volume":"94","author":"Gomes","year":"2019","journal-title":"Mater Sci Eng C."},{"key":"ref_25","first-page":"1","article-title":"Beclomethasone Dipropionate-Loaded Polymeric Nanocapsules: Development, In Vitro Cytotoxicity, and In Vivo Evaluation of Acute Lung Injury","volume":"14","author":"Chassot","year":"2014","journal-title":"J. Nanosci. Nanotechnol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.msec.2018.05.014","article-title":"Diphenyl diselenide loaded poly(\u03b5-caprolactone) nanocapsules with selective antimelanoma activity: Development and cytotoxic evaluation","volume":"91","author":"Ferreira","year":"2018","journal-title":"Mater. Sci. Eng. C."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"508","DOI":"10.3109\/02652048.2014.885603","article-title":"Poly (e-caprolactone) nanocapsules for oral delivery of raloxifene: Process optimization by hybrid design approach, in vitro and in vivo evaluation","volume":"31","author":"Aditya","year":"2014","journal-title":"J Microencapsul."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1590\/S0100-40422003000500017","article-title":"Caracteriza\u00e7\u00e3o e Estabilidade F\u00edsico-Qu\u00edmica de Sistemas Polim\u00e9ricos Nanoparticulados para Administra\u00e7\u00e3o de F\u00e1rmacos","volume":"26","author":"Schaffazick","year":"2003","journal-title":"Qu\u00edm. Nova"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.nano.2009.04.007","article-title":"Preparation and characterization of insulin nanoparticles using chitosan and Arabic gum with ionic gelation method","volume":"6","author":"Avadi","year":"2010","journal-title":"Nanomedicine"},{"key":"ref_30","first-page":"177","article-title":"Novel resveratrol nanodelivery systems based on lipid nanoparticles to enhance its oral bioavailability","volume":"8","author":"Neves","year":"2013","journal-title":"Int. J. Nanomed."},{"key":"ref_31","unstructured":"Maryadele, J.O.N., Patricia, E.H., Cherie, B.K., and Kristin, J.R. (2013). The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals, Royal Society of Chemistry."},{"key":"ref_32","unstructured":"Michael, D.L., Richard, J.L., and Robert, A.L. (1997). Hawley\u2019s Condensed Chemical Dictionary, John Wiley & Sons. [13rd ed.]."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.ijpharm.2009.10.018","article-title":"Polymer-based nanocapsules for drug delivery","volume":"385","author":"Fessi","year":"2010","journal-title":"Int. J. Pharm."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1080\/10717544.2017.1422298","article-title":"Preparation of curcumin self-micelle solid dispersion with enhanced bioavailability and cytotoxic activity by mechanochemistry","volume":"25","author":"Zhang","year":"2018","journal-title":"Drug Deliv."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2712","DOI":"10.1021\/jf205238x","article-title":"Nanoparticles Synthesized from Soy Protein: Preparation, Characterization, and Application for Nutraceutical Encapsulation","volume":"60","author":"Teng","year":"2012","journal-title":"J. Agric. Food Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1007\/s10973-012-2580-3","article-title":"Structural and thermal properties of spray-dried methotrexate-loaded biodegradable microparticles","volume":"112","author":"Oliveira","year":"2013","journal-title":"J. Therm. Anal. Calorim."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1100\/2012\/542937","article-title":"PHBV\/PCL Microparticles for Controlled Release of Resveratrol: Physicochemical Characterization, Antioxidant Potential, and Effect on Hemolysis of Human Erythrocytes","volume":"2012","author":"Mendes","year":"2012","journal-title":"Sci. World J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.ijpharm.2014.05.059","article-title":"Linolenic acid-modified PEG-PCL micelles for curcumin delivery","volume":"471","author":"Song","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s11671-015-1085-y","article-title":"Evaluation of High-Performance Curcumin Nanocrystals for Pulmonary Drug Delivery Both In Vitro and In Vivo","volume":"10","author":"Hu","year":"2015","journal-title":"Nanoscale Res. Lett."},{"key":"ref_40","unstructured":"Pucci, A., and Wandelt, K. (2009). Structural and Spectral Properties of Curcumin and Metal-Curcumin Complex Derived from Turmeric (Curcuma longa). Physics and Engineering of New Materials, Heidelberg, Germany, 15 January 2009, D.T., Springer."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.jphotobiol.2015.09.006","article-title":"Synthesis, characterization and in vitro evaluation of methotrexate conjugated fluorescent carbon nanoparticles as drug delivery system for human lung cancer targeting","volume":"153","author":"Ajmal","year":"2015","journal-title":"J. Photoch. Photobiol. B"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1590\/1414-431X20132643","article-title":"Developments in the use of nanocapsules in oncology","volume":"46","author":"Yurgel","year":"2013","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1590\/S1984-82502012000400020","article-title":"In vitro\/in vivo performance of different complexes of itraconazole used in the treatment of vaginal candidiasis","volume":"48","author":"Mirza","year":"2012","journal-title":"Braz. J. Pharm. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1016\/j.biochi.2013.04.004","article-title":"Augmented sensitivity to methotrexate by curcumin induced overexpression of folate receptor in KG-1 cells","volume":"95","author":"Dhanasekaran","year":"2013","journal-title":"Biochimie"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4802","DOI":"10.1016\/j.msec.2013.07.047","article-title":"The formulation and delivery of curcumin with lipid nanoparticles for the treatment of non-small cell lung cancer both in vitro and in vivo","volume":"33","author":"Wang","year":"2013","journal-title":"Mater. Sci. Eng. C."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.jcis.2010.05.022","article-title":"Fabrication of curcumin encapsulated PLGA nanoparticles for improved therapeutic effects in metastatic cancer cells","volume":"351","author":"Yallapu","year":"2010","journal-title":"Colloid Interface Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.ymeth.2007.01.003","article-title":"The sulphorhodamine (SRB) assay and other approaches to testing plant extracts and derived compounds for activities related to reputed anticancer activity","volume":"42","author":"Houghton","year":"2007","journal-title":"Methods"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.msec.2016.03.086","article-title":"Spray-dried Eudragit\u00ae\u00ae L100 microparticles containing ferulic acid: Formulation, in vitro cytoprotection and in vivo anti-platelet effect","volume":"64","author":"Nadal","year":"2016","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1002\/1520-6017(200105)90:5<647::AID-JPS1021>3.0.CO;2-G","article-title":"P-Glycoprotein Eflux Pump Expression and Activity in Calu-3 Cells","volume":"90","author":"Hamilton","year":"2001","journal-title":"J. Pharm. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1590\/S1984-82502012000300002","article-title":"Overview of P-glycoprotein inhibitors: A rational outlook","volume":"48","author":"Srivalli","year":"2012","journal-title":"Braz. J. Pharm. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1038\/35070009","article-title":"Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I","volume":"3","author":"Coleman","year":"2001","journal-title":"Nat. Cell. Biol."},{"key":"ref_52","first-page":"1","article-title":"The Synergistic In Vitro and In Vivo Antitumor Effect of Combination Therapy with Salinomycin and 5-Fluorouracil against Hepatocellular Carcinoma","volume":"9","author":"Wang","year":"2014","journal-title":"PLoS ONE"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1146\/annurev.physiol.60.1.619","article-title":"The mitochondrial death\/life regulator in apoptosis and necrosis","volume":"60","author":"Kroemer","year":"1998","journal-title":"Annu. Ver. Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0022-1759(02)00067-4","article-title":"Cell death during development","volume":"265","author":"Zakeri","year":"2002","journal-title":"J. Immunol. Methods"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1016\/0378-5173(89)90281-0","article-title":"Nanocapsule formation by interfacial polymer deposition following solvent displacement","volume":"55","author":"Fessi","year":"1989","journal-title":"Int. J. Pharm."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"},{"key":"ref_57","first-page":"1","article-title":"In vitro cytotoxic potential of essential oils of Eucalyptus benthamii and its related terpenes on tumor cell lines","volume":"2012","author":"Sartoratto","year":"2012","journal-title":"Evid. Based Complement Altern. Med."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Kifer, D., Jak\u0161i\u2019c, D., and Klari\u00b4c, M.\u0160. (2020). Assessing the Effect of Mycotoxin Combinations: Which Mathematical Model Is (the Most) Appropriate?. Toxins, 12.","DOI":"10.3390\/toxins12030153"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0022-1759(97)00137-3","article-title":"Optimization of the sulforhodamine B colorimetric assay","volume":"208","author":"Papazisis","year":"1997","journal-title":"J. Immunol. Methods"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1472-6750-5-12","article-title":"A simple technique for quantifying apoptosis in 96-well plates","volume":"5","author":"Ribble","year":"2005","journal-title":"BMC Biotechnol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/8\/1913\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:31:39Z","timestamp":1760362299000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/8\/1913"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,21]]},"references-count":60,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,4]]}},"alternative-id":["molecules25081913"],"URL":"https:\/\/doi.org\/10.3390\/molecules25081913","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,21]]}}}