{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T23:40:05Z","timestamp":1770680405978,"version":"3.49.0"},"reference-count":58,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T00:00:00Z","timestamp":1621814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004054","name":"King Abdulaziz University","doi-asserted-by":"publisher","award":["(RG-4\u2013166\u201341)."],"award-info":[{"award-number":["(RG-4\u2013166\u201341)."]}],"id":[{"id":"10.13039\/501100004054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Raloxifene hydrochloride (RLX), an antiosteoporotic agent, has been utilized for guarding against breast cancer and recently, for the disease management owing to its estrogen antagonist activity. Nevertheless, RLX exhibits poor bioavailability that could be attributed to reduced water solubility and first pass metabolism. To overcome these challenges, this study aimed at formulating and optimizing RLX emulsomes (RLX-EMLs) to enhance the drug antitumor activity. A 4131 factorial design was employed for assessing the effect of lipoid: solid lipid ratio and solid lipid type on the emulsomes characteristics. The anticancer potential of the optimized formulation and apoptotic parameters were assessed. Vesicle size, entrapment, and release efficiency were significantly influenced by both variables, while zeta potential was influenced by lipoid: solid lipid at p &lt; 0.05. The optimal formulation exhibited vesicle size of 236 \u00b1 8.6 nm, zeta potential of \u221218.6 \u00b1 0.7 mV, drug entrapment of 98.9 \u00b1 4.9%, and release efficiency of 42.7 \u00b1 1.8%. MTT assay showed concentration-dependent inhibition of MCF-7 cells viability. In addition, cells treated with RLX-EMLs showed significant arrest at G2\/M phase associated with significant increase in apoptotic and necrotic cells. The enhanced cytotoxic and anti-proliferative effect of RLX-EMLs relative to raw drug was authenticated through increased Bax\/Bcl-2 ratio, caspase-9 activation and depletion of mitochondrial membrane potential.<\/jats:p>","DOI":"10.3390\/pharmaceutics13060783","type":"journal-article","created":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T23:35:05Z","timestamp":1621899305000},"page":"783","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["RETRACTED: Lipidic Nano-Sized Emulsomes Potentiates the Cytotoxic and Apoptotic Effects of Raloxifene Hydrochloride in MCF-7 Human Breast Cancer Cells: Factorial Analysis and In Vitro Anti-Tumor Activity Assessment"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9067-8565","authenticated-orcid":false,"given":"Hibah","family":"Aldawsari","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3204-381X","authenticated-orcid":false,"given":"Osama","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"Mohamed Saeed Tamer Chair for Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3826-1519","authenticated-orcid":false,"given":"Nabil","family":"Alhakamy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"Mohamed Saeed Tamer Chair for Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2762-7108","authenticated-orcid":false,"given":"Thikryat","family":"Neamatallah","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6094-5570","authenticated-orcid":false,"given":"Usama","family":"Fahmy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"Mohamed Saeed Tamer Chair for Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1034-1653","authenticated-orcid":false,"given":"Shaimaa","family":"Badr-Eldin","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,24]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Breast cancer","volume":"5","author":"Harbeck","year":"2019","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.7150\/jca.13141","article-title":"Cancer hallmarks, biomarkers and breast cancer molecular subtypes","volume":"7","author":"Dai","year":"2016","journal-title":"J. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6325","DOI":"10.2147\/IJN.S181587","article-title":"In situ misemgel as a multifunctional dual-absorption platform for nasal delivery of raloxifene hydrochloride: Formulation, characterization, and in vivo performance","volume":"13","author":"Ahmed","year":"2018","journal-title":"Int. J. Nanomed."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Murthy, A., Rao Ravi, P., Kathuria, H., and Malekar, S. (2020). Oral Bioavailability Enhancement of Raloxifene with Nanostructured Lipid Carriers. Nanomaterials, 10.","DOI":"10.3390\/nano10061085"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1007\/s10549-012-2089-2","article-title":"Use of tamoxifen and raloxifene for breast cancer chemoprevention in 2010","volume":"134","author":"Waters","year":"2012","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1210\/me.2007-0340","article-title":"Differential regulation of native estrogen receptor-regulatory elements by estradiol, tamoxifen, and raloxifene","volume":"22","author":"Levy","year":"2008","journal-title":"Mol. Endocrinol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Wang, Z., and Li, Y. (2018). Raloxifene\/SBE-\u03b2-CD inclusion complexes formulated into nanoparticles with chitosan to overcome the absorption barrier for bioavailability enhancement. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10030076"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1208\/s12249-017-0919-6","article-title":"Self-Assembling Raloxifene Loaded Mixed Micelles: Formulation Optimization, In Vitro Cytotoxicity and In Vivo Pharmacokinetics","volume":"19","author":"Kanade","year":"2018","journal-title":"AAPS PharmSciTech"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s12951-018-0392-8","article-title":"Nano based drug delivery systems: Recent developments and future prospects 10 Technology 1007 Nanotechnology 03 Chemical Sciences 0306 Physical Chemistry (incl. Structural) 03 Chemical Sciences 0303 Macromolecular and Materials Chemistry 11 Medical and Health Sciences 1115 Pharmacology and Pharmaceutical Sciences 09 Engineering 0903 Biomedical Engineering Prof Ueli Aebi, Prof Peter Gehr","volume":"16","author":"Patra","year":"2018","journal-title":"J. Nanobiotechnol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Su, Y.L., and Hu, S.H. (2018). Functional nanoparticles for tumor penetration of therapeutics. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10040193"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"62","DOI":"10.3109\/08982104.2011.592495","article-title":"Development and evaluation of tripalmitin emulsomes for the treatment of experimental visceral leishmaniasis","volume":"22","author":"Pal","year":"2012","journal-title":"J. Liposome Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.ijpharm.2016.02.038","article-title":"Identifying lipidic emulsomes for improved oxcarbazepine brain targeting: In vitro and rat in vivo studies","volume":"503","author":"Soliman","year":"2016","journal-title":"Int. J. Pharm."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1080\/10611860701195395","article-title":"Development and characterization of amphotericin B bearing emulsomes for passive and active macrophage targeting","volume":"15","author":"Gupta","year":"2007","journal-title":"J. Drug Target."},{"key":"ref_14","first-page":"133","article-title":"Emulsomes: An Emerging Vesicular Drug Delivery System","volume":"3","author":"Kumar","year":"2013","journal-title":"J. Drug Deliv. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1007\/s12272-015-0630-7","article-title":"Preparation and performance evaluation of emulsomes as a drug delivery system for silybin","volume":"38","author":"Zhou","year":"2015","journal-title":"Arch. Pharm. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1080\/08982104.2019.1570250","article-title":"PEGylated trimethylchitosan emulsomes conjugated to octreotide for targeted delivery of sorafenib to hepatocellular carcinoma cells of HepG2","volume":"29","author":"Varshosaz","year":"2019","journal-title":"J. Liposome Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"50","DOI":"10.3389\/fbioe.2020.00050","article-title":"Curcumin- and Piperine-Loaded Emulsomes as Combinational Treatment Approach Enhance the Anticancer Activity of Curcumin on HCT116 Colorectal Cancer Model","volume":"8","author":"Bolat","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"392","DOI":"10.2174\/138920101604150218112656","article-title":"Emulsomes Meet S-layer Proteins: An Emerging Targeted Drug Delivery System","volume":"16","author":"Ucisik","year":"2015","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Awan, Z.A., Fahmy, U.A., Badr-eldin, S.M., Ibrahim, T.S., Asfour, H.Z., Al-rabia, M.W., Alfarsi, A., Alhakamy, N.A., Abdulaal, W.H., and Al Sadoun, H. (2020). The enhanced cytotoxic and pro-apoptotic effects of optimized simvastatin-loaded emulsomes on MCF-7 breast cancer cells. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12070597"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Alhakamy, N.A., Badr-Eldin, S.M., Ahmed, O.A.A., Asfour, H.Z., Aldawsari, H.M., Algandaby, M.M., Eid, B.G., Abdel-Naim, A.B., Awan, Z.A., and Alghaith, A.F. (2020). Piceatannol-loaded emulsomes exhibit enhanced cytostatic and apoptotic activities in colon cancer cells. Antioxidants, 9.","DOI":"10.3390\/antiox9050419"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Fahmy, U.A., Aldawsari, H.M., Badr-Eldin, S.M., Ahmed, O.A.A., Alhakamy, N.A., Alsulimani, H.H., Caraci, F., and Caruso, G. (2020). The Encapsulation of Febuxostat into Emulsomes Strongly Enhances the Cytotoxic Potential of the Drug on HCT 116 Colon Cancer Cells. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12100956"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ahmed, O.A.A., Fahmy, U.A., Badr-Eldin, S.M., Aldawsari, H.M., Awan, Z.A., Asfour, H.Z., Kammoun, A.K., Caruso, G., Caraci, F., and Alfarsi, A. (2020). Application of nanopharmaceutics for flibanserin brain delivery augmentation via the nasal route. Nanomaterials, 10.","DOI":"10.3390\/nano10071270"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.ijpharm.2009.06.026","article-title":"Engineered chylomicron mimicking carrier emulsome for lymph targeted oral delivery of methotrexate","volume":"380","author":"Paliwal","year":"2009","journal-title":"Int. J. Pharm."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Alhakamy, N.A., Ahmed, O.A.A., Fahmy, U.A., and Md, S. (2021). Development and in vitro evaluation of 2-methoxyestradiol loaded polymeric micelles for enhancing anticancer activities in prostate cancer. Polymers, 13.","DOI":"10.3390\/polym13060884"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.lfs.2016.08.033","article-title":"Development of risperidone liposomes for brain targeting through intranasal route","volume":"163","author":"Narayan","year":"2016","journal-title":"Life Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.phrs.2005.05.007","article-title":"HPLC analysis of raloxifene hydrochloride and its application to drug quality control studies","volume":"52","author":"Trontelj","year":"2005","journal-title":"Pharmacol. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"178","DOI":"10.3109\/03639045.2010.502534","article-title":"Standardized in vitro drug release test for colloidal drug carriers using modified USP dissolution apparatus i","volume":"37","author":"Lamprecht","year":"2011","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Darwesh, B., Aldawsari, H.M., and Badr-Eldin, S.M. (2018). Optimized chitosan\/anion polyelectrolyte complex based inserts for vaginal delivery of fluconazole: In vitro\/in vivo evaluation. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10040227"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3181","DOI":"10.3109\/10717544.2016.1160458","article-title":"Localized rosuvastatin via implantable bioerodible sponge and its potential role in augmenting bone healing and regeneration","volume":"23","author":"Ibrahim","year":"2016","journal-title":"Drug Deliv."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.jare.2020.04.019","article-title":"Enhanced pharmacokinetic performance of dapoxetine hydrochloride via the formulation of instantly-dissolving buccal films with acidic pH modifier and hydrophilic cyclodextrin: Factorial analysis, in vitro and in vivo assessment","volume":"24","author":"Aldawsari","year":"2020","journal-title":"J. Adv. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.ijpharm.2015.03.033","article-title":"Investigating the potential of employing bilosomes as a novel vesicular carrier for transdermal delivery of tenoxicam","volume":"485","author":"Abdelbary","year":"2015","journal-title":"Int. J. Pharm."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1080\/10837450.2018.1474221","article-title":"Preparation of biocompatible copolymeric micelles as a carrier of atorvastatin and rosuvastatin for potential anticancer activity study","volume":"24","author":"Alimohammadi","year":"2019","journal-title":"Pharm. Dev. Technol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Franco, M.S., Roque, M.C., and Oliveira, M.C. (2019). Short and long-term effects of the exposure of breast cancer cell lines to different ratios of free or co-encapsulated liposomal paclitaxel and doxorubicin. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11040178"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.toxrep.2017.07.010","article-title":"Farnesiferol C induces cell cycle arrest and apoptosis mediated by oxidative stress in MCF-7 cell line","volume":"4","author":"Hasanzadeh","year":"2017","journal-title":"Toxicol. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"18359","DOI":"10.1039\/C9RA03130H","article-title":"Induction of cell cycle arrest and apoptosis by copper complex Cu (SBCM) 2 towards oestrogen-receptor positive MCF-7 breast cancer cells","volume":"9","author":"Foo","year":"2019","journal-title":"RSC Adv."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.jsps.2017.04.036","article-title":"Study on apoptosis effect of human breast cancer cell MCF-7 induced by lycorine hydrochloride via death receptor pathway","volume":"25","author":"Ji","year":"2017","journal-title":"Saudi Pharm. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"673","DOI":"10.2217\/nnm.16.5","article-title":"The effect of nanoparticle size on in vivo pharmacokinetics and cellular interaction","volume":"11","author":"Hoshyar","year":"2016","journal-title":"Nanomedicine"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1038\/nbt.3330","article-title":"Principles of nanoparticle design for overcoming biological barriers to drug delivery","volume":"33","author":"Blanco","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Ramalho, M.J., Loureiro, J.A., Coelho, M.A.N., and Pereira, M.C. (2019). Factorial design as a tool for the optimization of plga nanoparticles for the co-delivery of temozolomide and o6-benzylguanine. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11080401"},{"key":"ref_40","first-page":"167","article-title":"Optimization and physicochemical characterization of a triamcinolone acetonide-loaded NLC for ocular antiangiogenic applications","volume":"393","author":"Egea","year":"2010","journal-title":"Int. J. Pharm."},{"key":"ref_41","unstructured":"Riffenburgh, R. (2012). Statistics in Medicine, Elsevier Inc."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Ahmed, O.A.A., and Badr-Eldin, S.M. (2020). Biodegradable self-assembled nanoparticles of PEG-PLGA amphiphilic diblock copolymer as a promising stealth system for augmented vinpocetine brain delivery. Int. J. Pharm., 588.","DOI":"10.1016\/j.ijpharm.2020.119778"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Jain, A., and Jain, S.K. (2013). Formulation and optimization of temozolomide nanoparticles by 3 factor 2 level factorial design. Biomatter, 3.","DOI":"10.4161\/biom.25102"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1211\/jpp.58.3.0005","article-title":"Development and characterization of emulsomes for sustained and targeted delivery of an antiviral agent to liver","volume":"58","author":"Vyas","year":"2006","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Danaei, M., Dehghankhold, M., Ataei, S., Hasanzadeh Davarani, F., Javanmard, R., Dokhani, A., Khorasani, S., and Mozafari, M.R. (2018). Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10020057"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.jddst.2018.10.027","article-title":"Intranasal optimized solid lipid nanoparticles loaded in situ gel for enhancing trans-mucosal delivery of simvastatin","volume":"48","author":"Ahmed","year":"2018","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.2147\/DDDT.S129008","article-title":"Development of antiproliferative long-circulating liposomes co-encapsulating doxorubicin and curcumin, through the use of a quality-by-design approach","volume":"11","author":"Tefas","year":"2017","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.colsurfb.2010.07.020","article-title":"Curcuminoids-loaded lipid nanoparticles: Novel approach towards malaria treatment","volume":"81","author":"Nayak","year":"2010","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Gim, S., Ong, M., Ming, L.C., Lee, K.S., and Yuen, K.H. (2016). Influence of the Encapsulation Efficiency and Size of Liposome on the Oral Bioavailability of Griseofulvin-Loaded Liposomes. J. Pharm., 8.","DOI":"10.3390\/pharmaceutics8030025"},{"key":"ref_50","first-page":"17","article-title":"Development and Optimization of Liposomes Containing 5 Fluorouracil and Tretinoin for Skin Warts: 32 Experimental Design","volume":"44","author":"Tiwari","year":"2019","journal-title":"J. Pharm."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.jsps.2017.10.012","article-title":"Applications of nanoparticle systems in drug delivery technology","volume":"26","author":"Rizvi","year":"2018","journal-title":"Saudi Pharm. J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"138","DOI":"10.14348\/molcells.2015.2193","article-title":"Raloxifene induces autophagy-dependent cell death in breast cancer cells via the activation of amp-activated protein kinase","volume":"38","author":"Kim","year":"2015","journal-title":"Mol. Cells"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1080\/15384047.2015.1095409","article-title":"Reversal effects of Raloxifene on paclitaxel resistance in 2 MDR breast cancer cells","volume":"16","author":"Xu","year":"2015","journal-title":"Cancer Biol. Ther."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"385","DOI":"10.3892\/ijo.2015.3252","article-title":"A novel curcumin derivative increases the cytotoxicity of raloxifene in estrogen receptor-negative breast cancer cell lines","volume":"48","author":"Taurin","year":"2016","journal-title":"Int. J. Oncol."},{"key":"ref_55","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_56","doi-asserted-by":"crossref","first-page":"2861","DOI":"10.1038\/sj.onc.1207523","article-title":"Toxic proteins released from mitochondria in cell death","volume":"23","author":"Saelens","year":"2004","journal-title":"Oncogene"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/nrc883","article-title":"The BCL2 family: Regulators of the cellular life-or-death switch","volume":"2","author":"Cory","year":"2002","journal-title":"Nat. Rev. Cancer"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/j.bbrc.2003.09.109","article-title":"Bax conformational change is a crucial step for PUMA-mediated apoptosis in human leukemia","volume":"310","author":"Liu","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."}],"updated-by":[{"DOI":"10.3390\/pharmaceutics16020195","type":"retraction","label":"Retraction","source":"retraction-watch","updated":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T00:00:00Z","timestamp":1706572800000},"record-id":"51439"},{"DOI":"10.3390\/pharmaceutics16020195","type":"retraction","label":"Retraction","source":"publisher","updated":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T00:00:00Z","timestamp":1621814400000}}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/13\/6\/783\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,3]],"date-time":"2025-08-03T22:25:32Z","timestamp":1754259932000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/13\/6\/783"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,24]]},"references-count":58,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["pharmaceutics13060783"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics13060783","relation":{"retraction":[{"id-type":"doi","id":"10.3390\/pharmaceutics16020195","asserted-by":"object"}]},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,24]]}}}