{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T10:02:07Z","timestamp":1779789727035,"version":"3.53.1"},"reference-count":67,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100009367","name":"Mansoura University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100009367","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Combination therapy has emerged as a standard strategy for enhancing the efficacy of anticancer treatments. The purpose of our study was to assess the melatonin-selenium nanoparticles\u2019 anticancer potential (MSeNPs) in a murine model of Ehrlich ascites carcinoma (EAC). Assessments included cell viability, hematological parameters, oxidative stress markers, apoptosis, cell cycle dynamics, and pro-inflammatory cytokines. Our findings demonstrate that MSeNPs inhibit tumor growth and enhance antioxidant defenses. MSeNPs significantly reduce IL-6 levels, alleviating EAC-associated inflammation. Furthermore, MSeNPs induced apoptosis through caspase-3 activation and Ki-67 downregulation, resulting in decreased cell proliferation and significant G0\/G1 cell cycle arrest, accompanied by marked suppression of the S phase. In conclusion, these results highlight the synergistic therapeutic advantage of MSeNPs, indicating greater efficacy than monotherapies with melatonin, selenium, or selenium nanoparticles alone. MSeNPs hold promise as a potent, multi-targeted agent for future cancer therapies.<\/jats:p>","DOI":"10.1038\/s41598-026-53359-w","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T07:15:22Z","timestamp":1779779722000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Melatonin\u2013selenium nanoformulation: a promising therapeutic strategy against Ehrlich ascites carcinoma"],"prefix":"10.1038","volume":"16","author":[{"given":"Hanaa M.","family":"Morad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. F.","family":"Abdel-Aziz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai M.","family":"Madkour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"53359_CR1","first-page":"e58","volume":"2","author":"CL Putta","year":"2023","unstructured":"Putta, C. L., Eswar, K., Rengan, A. K. & Melatonin Avenues in cancer therapy and its nanotechnological advancements. MedComm - Biomater. appl. 2, e58 (2023).","journal-title":"MedComm - Biomater. appl."},{"key":"53359_CR2","doi-asserted-by":"crossref","unstructured":"Patel, M., Joshi, G. & Sawant, K. K. Nanotechnology in oral drug delivery: Salient aspects, state of art, and applications pp.165\u2013184 (From Biomolecules to Nanoparticles, 2020).","DOI":"10.1007\/978-3-030-41464-1_8"},{"key":"53359_CR3","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1186\/s12906-023-04279-z","volume":"23","author":"TS Aldayel","year":"2023","unstructured":"Aldayel, T. S. et al. Evaluation of antioxidant, anti-inflammatory, anticancer activities and molecular docking of Moringa oleifera seed oil extract against experimental model of Ehrlich ascites carcinoma in Swiss female albino mice. BMC Complement. Med. Ther. 23, 457 (2023).","journal-title":"BMC Complement. Med. Ther."},{"key":"53359_CR4","doi-asserted-by":"publisher","first-page":"6624","DOI":"10.3390\/molecules28186624","volume":"28","author":"S Malik","year":"2023","unstructured":"Malik, S., Muhammad, K. & Waheed, Y. Emerging applications of nanotechnology in healthcare and medicine. Molecules 28, 6624 (2023).","journal-title":"Molecules"},{"key":"53359_CR5","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.3390\/pharmaceutics15031025","volume":"15","author":"N Alrushaid","year":"2023","unstructured":"Alrushaid, N., Khan, F. A., Al-Suhaimi, E. A. & Elaissari, A. Nanotechnology in cancer diagnosis and treatment. Pharmaceutics 15, 1025 (2023).","journal-title":"Pharmaceutics"},{"key":"53359_CR6","doi-asserted-by":"publisher","first-page":"2437","DOI":"10.1007\/s10571-023-01324-w","volume":"43","author":"SB Ahmad","year":"2023","unstructured":"Ahmad, S. B. et al. Melatonin and health: insights of melatonin action, biological functions, and associated disorders. Cell. Mol. Neurobiol. 43, 2437\u20132458 (2023).","journal-title":"Cell. Mol. Neurobiol"},{"key":"53359_CR7","doi-asserted-by":"publisher","first-page":"e12926","DOI":"10.1111\/jpi.12926","volume":"76","author":"JA Boutin","year":"2024","unstructured":"Boutin, J. A., Liberelle, M., Yous, S., Ferry, G. & Nepveu, F. Melatonin facts: Lack of evidence that melatonin is a radical scavenger in living systems. J. Pineal Res. 76, e12926 (2024).","journal-title":"J. Pineal Res."},{"key":"53359_CR8","doi-asserted-by":"publisher","first-page":"3263","DOI":"10.3390\/cancers13133263","volume":"13","author":"AV Gonz\u00e1lez Cabeza","year":"2021","unstructured":"Gonz\u00e1lez Cabeza, A. V., Alonso Gonz\u00e1lez, C., Gonz\u00e1lez Gonz\u00e1lez, A., Men\u00e9ndez Men\u00e9ndez, J. & Cos Corral, S. Mart\u00ednez Campa, C.M. Melatonin as an adjuvant to antiangiogenic cancer treatments. Cancers 13, 3263 (2021).","journal-title":"Cancers"},{"key":"53359_CR9","doi-asserted-by":"publisher","first-page":"19837","DOI":"10.1038\/s41598-024-70791-y","volume":"14","author":"E Kaya-Tilki","year":"2024","unstructured":"Kaya-Tilki, E., \u00d6zt\u00fcrk, A. A., Eng\u00fcr-\u00d6zt\u00fcrk, S. & Dikmen, M. Enhanced anti-angiogenic effects of aprepitant-loaded nanoparticles in human umbilical vein endothelial cells. Sci. Rep. 14, 19837 (2024).","journal-title":"Sci. Rep."},{"key":"53359_CR10","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1080\/03602532.2024.2305764","volume":"56","author":"YJ Yi","year":"2024","unstructured":"Yi, Y. J. et al. Melatonin in cancer biology: Pathways, derivatives, and the promise of targeted delivery. Drug Metab. Rev. 56, 62\u201379 (2024).","journal-title":"Drug Metab. Rev."},{"key":"53359_CR11","doi-asserted-by":"publisher","first-page":"e0261341","DOI":"10.1371\/journal.pone.0261341","volume":"17","author":"A Nyamsambuu","year":"2022","unstructured":"Nyamsambuu, A., Khan, M. A., Zhou, X. & Chen, H. C. Molecular mechanism of inhibitory effects of melatonin on prostate cancer cell proliferation, migration and invasion. PLoS One. 17, e0261341 (2022).","journal-title":"PLoS One"},{"key":"53359_CR12","doi-asserted-by":"publisher","first-page":"2019","DOI":"10.2147\/OTT.S298512","volume":"14","author":"S Gurunathan","year":"2021","unstructured":"Gurunathan, S., Qasim, M., Kang, M. H. & Kim, J. H. Role and therapeutic potential of melatonin in various type of cancers. Onco Targets Ther. 14, 2019\u20132052 (2021).","journal-title":"Onco Targets Ther."},{"key":"53359_CR13","doi-asserted-by":"publisher","first-page":"30","DOI":"10.3390\/diseases9020030","volume":"9","author":"VM Mart\u00edn Gim\u00e9nez","year":"2021","unstructured":"Mart\u00edn Gim\u00e9nez, V. M. et al. Potential effects of melatonin and micronutrients on mitochondrial dysfunction during a cytokine storm typical of oxidative\/inflammatory diseases. Diseases 9, 30 (2021).","journal-title":"Diseases"},{"key":"53359_CR14","doi-asserted-by":"publisher","first-page":"251","DOI":"10.3390\/antiox11020251","volume":"11","author":"G Barchielli","year":"2022","unstructured":"Barchielli, G., Capperucci, A. & Tanini, D. The role of selenium in pathologies: an updated review. Antioxidants 11, 251 (2022).","journal-title":"Antioxidants"},{"key":"53359_CR15","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s12935-022-02472-7","volume":"22","author":"M Mirza-Aghazadeh-Attari","year":"2022","unstructured":"Mirza-Aghazadeh-Attari, M., Mihanfar, A., Yousefi, B. & Majidinia, M. Nanotechnology-based advances in the efficient delivery of melatonin. Cancer Cell. Int. 22, 43 (2022).","journal-title":"Cancer Cell. Int."},{"key":"53359_CR16","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.bmt.2023.12.001","volume":"6","author":"KK Karthik","year":"2024","unstructured":"Karthik, K. K., Cheriyan, B. V., Rajeshkumar, S. & Gopalakrishnan, M. A review on selenium nanoparticles and their biomedical applications. Biomed. Technol. 6, 61\u201374 (2024).","journal-title":"Biomed. Technol."},{"key":"53359_CR17","doi-asserted-by":"publisher","first-page":"2100598","DOI":"10.1002\/adhm.202100598","volume":"10","author":"C Ferro","year":"2021","unstructured":"Ferro, C., Florindo, H. F. & Santos, H. A. Selenium nanoparticles for biomedical applications: from development and characterization to therapeutics. Adv. Healthc. Mater. 10, 2100598 (2021).","journal-title":"Adv. Healthc. Mater."},{"key":"53359_CR18","doi-asserted-by":"publisher","first-page":"799","DOI":"10.3390\/biom13050799","volume":"13","author":"F Zhang","year":"2013","unstructured":"Zhang, F., Li, X. & Wei, Y. Selenium and selenoproteins in health. Biomolecules 13, 799 (2013).","journal-title":"Biomolecules"},{"key":"53359_CR19","doi-asserted-by":"publisher","first-page":"127235","DOI":"10.1016\/j.jtemb.2023.127235","volume":"79","author":"N Hadrup","year":"2023","unstructured":"Hadrup, N. & Ravn-Haren, G. Toxicity of repeated oral intake of organic selenium, inorganic selenium, and selenium nanoparticles: A review. J. Trace Elem. Med. Biol. 79, 127235 (2023).","journal-title":"J. Trace Elem. Med. Biol."},{"key":"53359_CR20","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1111\/j.1600-079X.2005.00231.x","volume":"39","author":"H Wang","year":"2005","unstructured":"Wang, H. et al. Melatonin-selenium nanoparticles inhibit oxidative stress and protect against hepatic injury induced by Bacillus Calmette\u2013Gu\u00e9rin\/lipopolysaccharide in mice. J. Pineal Res. 39, 156\u2013163 (2005).","journal-title":"J. Pineal Res."},{"key":"53359_CR21","doi-asserted-by":"publisher","first-page":"3","DOI":"10.3390\/futurepharmacol5010003","volume":"5","author":"TPDS Oliveira","year":"2025","unstructured":"Oliveira, T. P. D. S., Lima, A. K. O. & Muehlmann, L. A. An updated review of the antimicrobial potential of selenium nanoparticles and selenium-related toxicological issues. Future pharmacol. 5, 3 (2025).","journal-title":"Future pharmacol."},{"key":"53359_CR22","doi-asserted-by":"publisher","first-page":"6236","DOI":"10.33263\/BRIAC105.62366244","volume":"10","author":"AM Abdelghany","year":"2020","unstructured":"Abdelghany, A. M., Ayaad, D. M. & Mahmoud, S. M. Antibacterial and energy gap correlation of PVA\/SA biofilms doped with selenium nanoparticles. Biointerface Res. Appl. Chem. 10, 6236\u20136244 (2020).","journal-title":"Biointerface Res. Appl. Chem."},{"key":"53359_CR23","doi-asserted-by":"publisher","first-page":"613","DOI":"10.3233\/BME-171705","volume":"28","author":"Y Amini","year":"2017","unstructured":"Amini, Y. et al. Different methods to determine the encapsulation efficiency of protein in PLGA nanoparticles. Bio-Med Mater. Eng. 28, 613\u2013620 (2017).","journal-title":"Bio-Med Mater. Eng."},{"key":"53359_CR24","doi-asserted-by":"publisher","first-page":"100029","DOI":"10.1016\/j.adcanc.2022.100029","volume":"4","author":"NGS Gowda","year":"2022","unstructured":"Gowda, N. G. S. et al. Ehrlich Ascites carcinoma mice model for studying liver inflammation and fibrosis. Adv. Cancer Biol. \u2013 Metastasis. 4, 100029 (2022).","journal-title":"Adv. Cancer Biol. \u2013 Metastasis"},{"key":"53359_CR25","doi-asserted-by":"publisher","first-page":"6494","DOI":"10.1038\/s41598-022-10517-0","volume":"12","author":"AA Attia","year":"2022","unstructured":"Attia, A. A. et al. Amygdalin potentiates the anti-cancer effect of Sorafenib on Ehrlich ascites carcinoma and ameliorates the associated liver damage. Sci. Rep. 12, 6494 (2022).","journal-title":"Sci. Rep."},{"key":"53359_CR26","doi-asserted-by":"publisher","first-page":"428","DOI":"10.4049\/jimmunol.79.5.428","volume":"79","author":"WF McLimans","year":"1957","unstructured":"McLimans, W. F., Davis, E. V., Glover, F. L. & Rake, G. W. The submerged culture of mammalian cells: the spinner culture. J. Immunol. 79, 428\u2013433 (1957).","journal-title":"J. Immunol."},{"key":"53359_CR27","first-page":"194","volume":"6","author":"MH Hadwan","year":"2016","unstructured":"Hadwan, M. H. & Abed, H. N. Data supporting the spectrophotometric method for the estimation of catalase activity. DIB 6, 194\u2013199 (2016).","journal-title":"DIB"},{"key":"53359_CR28","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1016\/S0006-291X(72)80218-3","volume":"46","author":"M Nishikimi","year":"1972","unstructured":"Nishikimi, M., Rao, N. A. & Yagi, K. Measurement of superoxide dismutase. Biochem. Biophys. Res. Commun. 46, 849\u2013854 (1972).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"53359_CR29","first-page":"158","volume":"70","author":"DE Paglia","year":"1967","unstructured":"Paglia, D. E. & Valentine, W. N. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J. Lab. Clin. Med. 70, 158\u2013169 (1967).","journal-title":"J. Lab. Clin. Med."},{"key":"53359_CR30","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/0003-2697(79)90738-3","volume":"95","author":"H Ohkawa","year":"1979","unstructured":"Ohkawa, H., Ohishi, N. & Yagi, K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem. 95, 351\u2013358 (1979).","journal-title":"Anal. Biochem."},{"key":"53359_CR31","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/0003-2697(82)90118-X","volume":"126","author":"LC Green","year":"1982","unstructured":"Green, L. C. et al. Analysis of nitrate, nitrite, and [15\u00a0N] nitrate in biological fluids. Anal. Biochem. 126, 131\u2013138 (1982).","journal-title":"Anal. Biochem."},{"key":"53359_CR32","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1136\/jclinpath-2012-201085","volume":"66","author":"N Pathmanathan","year":"2013","unstructured":"Pathmanathan, N. & Balleine, R. L. Ki67 and proliferation in breast cancer. J. Clin. Pathol. 66, 512\u2013516 (2013).","journal-title":"J. Clin. Pathol."},{"key":"53359_CR33","doi-asserted-by":"publisher","first-page":"114643","DOI":"10.1016\/j.biopha.2023.114643","volume":"162","author":"C Duan","year":"2023","unstructured":"Duan, C. et al. Overcoming Cancer Multi-drug Resistance (MDR): Reasons, mechanisms, nanotherapeutic solutions, and challenges. Biomed. Pharmacother. 162, 114643 (2023).","journal-title":"Biomed. Pharmacother"},{"key":"53359_CR34","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1007\/s10876-019-01671-z","volume":"31","author":"H Vahidi","year":"2020","unstructured":"Vahidi, H., Barabadi, H. & Saravanan, M. Emerging selenium nanoparticles to combat cancer: a systematic review. J. Clust Sci. 31, 301\u2013309 (2020).","journal-title":"J. Clust Sci."},{"key":"53359_CR35","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1139\/y03-026","volume":"81","author":"K Skwarlo-Sonta","year":"2003","unstructured":"Skwarlo-Sonta, K., Majewski, P., Markowska, M., Oblap, R. & Olszanska, B. Bidirectional communication between the pineal gland and the immune system. Can. J. Physiol. Pharmacol. 81, 342\u2013349 (2003).","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"53359_CR36","doi-asserted-by":"crossref","unstructured":"Reiter, R. J., Ma, Q. & Sharma, R. Melatonin in mitochondria: mitigating clear and present dangers. Physiology. 35, 86\u201395 (2020).","DOI":"10.1152\/physiol.00034.2019"},{"key":"53359_CR37","doi-asserted-by":"publisher","first-page":"3805","DOI":"10.2174\/092986712801661013","volume":"19","author":"M S\u00e1nchez-Hidalgo","year":"2012","unstructured":"S\u00e1nchez-Hidalgo, M., Guerrero, M., Villegas, J. & Packham, I. A de la Lastra, C. Melatonin, a natural programmed cell death inducer in cancer. Curr. Med. Chem. 19, 3805\u20133821 (2012).","journal-title":"Curr. Med. Chem."},{"key":"53359_CR38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12964-023-01047-x","volume":"21","author":"A Mafi","year":"2023","unstructured":"Mafi, A. et al. Melatonin and 5-fluorouracil combination chemotherapy: opportunities and efficacy in cancer therapy. Cell. Commun. Signal. 21, 1\u201317 (2023).","journal-title":"Cell. Commun. Signal."},{"key":"53359_CR39","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/S0304-3835(99)00366-3","volume":"151","author":"MA El-Missiry","year":"2000","unstructured":"El-Missiry, M. A. & Abd El-Aziz, A. F. Influence of melatonin on proliferation and antioxidant system in Ehrlich ascites carcinoma cells. Cancer Lett. 151, 119\u2013125 (2000).","journal-title":"Cancer Lett."},{"key":"53359_CR40","doi-asserted-by":"publisher","first-page":"3779","DOI":"10.3390\/ijms23073779","volume":"23","author":"L Wang","year":"2022","unstructured":"Wang, L., Wang, C. & Choi, W. S. Use of melatonin in cancer treatment: where are we? Int. J. Mol. Sci. 23, 3779 (2022).","journal-title":"Int. J. Mol. Sci."},{"key":"53359_CR41","doi-asserted-by":"publisher","first-page":"17767","DOI":"10.1021\/acsomega.0c02448","volume":"5","author":"SV Gudkov","year":"2020","unstructured":"Gudkov, S. V. et al. Production and use of selenium nanoparticles as fertilizers. ACS omega. 5, 17767\u201317774 (2020).","journal-title":"ACS omega"},{"key":"53359_CR42","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1016\/S0891-5849(03)00428-3","volume":"35","author":"B Huang","year":"2003","unstructured":"Huang, B., Zhang, J., Hou, J. & Chen, C. Free radical scavenging efficiency of Nano-Se in vitro. Free Radic Biol. Med. 35, 805\u2013813 (2003).","journal-title":"Free Radic Biol. Med."},{"key":"53359_CR43","doi-asserted-by":"publisher","first-page":"7106","DOI":"10.1016\/j.biomaterials.2013.04.067","volume":"34","author":"Y Huang","year":"2013","unstructured":"Huang, Y. et al. Selective cellular uptake and induction of apoptosis of cancer-targeted selenium nanoparticles. Biomater 34, 7106\u20137116 (2013).","journal-title":"Biomater"},{"key":"53359_CR44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2014.04.003","volume":"72","author":"X Wang","year":"2014","unstructured":"Wang, X., Sun, K., Tan, Y., Wu, S. & Zhang, J. Efficacy and safety of selenium nanoparticles administered intraperitoneally for the prevention of growth of cancer cells in the peritoneal cavity. Free Radic Biol. Med. 72, 1\u201310 (2014).","journal-title":"Free Radic Biol. Med."},{"key":"53359_CR45","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1016\/j.colsurfb.2012.02.006","volume":"94","author":"H Luo","year":"2012","unstructured":"Luo, H., Wang, F., Bai, Y., Chen, T. & Zheng, W. Selenium nanoparticles inhibit the growth of HeLa and MDA-MB-231 cells through induction of S phase arrest. Colloids Surf. B: Biointerfaces. 94, 304\u2013308 (2012).","journal-title":"Colloids Surf. B: Biointerfaces"},{"key":"53359_CR46","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1016\/j.biopha.2018.12.146","volume":"111","author":"A Khurana","year":"2019","unstructured":"Khurana, A., Tekula, S., Saifi, M. A., Venkatesh, P. & Godugu, C. Therapeutic applications of selenium nanoparticles. Biomed. Pharmacother. 111, 802\u2013812 (2019).","journal-title":"Biomed. Pharmacother"},{"key":"53359_CR47","first-page":"3389","volume":"10","author":"MS Ahmad","year":"2015","unstructured":"Ahmad, M. S., Yasser, M. M., Sholkamy, E. N., Ali, A. M. & Mehanni, M. M. Anticancer activity of biostabilized selenium nanorods synthesized by Streptomyces bikiniensis strain Ess_amA-1. Int. J. Nanomed. 10, 3389\u20133401 (2015).","journal-title":"Int. J. Nanomed."},{"key":"53359_CR48","doi-asserted-by":"publisher","first-page":"3126","DOI":"10.1007\/s12011-020-02431-1","volume":"199","author":"MF Abd El-Kader","year":"2021","unstructured":"Abd El-Kader, M. F. et al. Selenium nanoparticles act potentially on the growth performance, hemato-biochemical indices, antioxidative, and immune-related genes of European seabass (Dicentrarchus labrax). Biol. Trace Elem. Res. 199, 3126\u20133134 (2021).","journal-title":"Biol. Trace Elem. Res."},{"key":"53359_CR49","doi-asserted-by":"publisher","first-page":"2506","DOI":"10.3390\/molecules26092506","volume":"26","author":"WH Talib","year":"2021","unstructured":"Talib, W. H., Alsayed, A. R., Abuawad, A., Daoud, S. & Mahmod, A. I. Melatonin in cancer treatment: current knowledge and future opportunities. Mol 26, 2506 (2021).","journal-title":"Mol"},{"key":"53359_CR50","doi-asserted-by":"publisher","first-page":"642","DOI":"10.3390\/antiox10050642","volume":"10","author":"S Arfin","year":"2021","unstructured":"Arfin, S. et al. Oxidative stress in cancer cell metabolism. Antioxidants 10, 642 (2021).","journal-title":"Antioxidants"},{"key":"53359_CR51","doi-asserted-by":"publisher","first-page":"114297","DOI":"10.1016\/j.jep.2021.114297","volume":"278","author":"MM Rahman","year":"2021","unstructured":"Rahman, M. M. et al. Unfolding the apoptotic mechanism of antioxidant enriched-leaves of Tabebuia pallida (lindl.) miers in EAC cells and mouse model. J. Ethnopharmacol. 278, 114297 (2021).","journal-title":"J. Ethnopharmacol."},{"key":"53359_CR52","doi-asserted-by":"publisher","first-page":"1916","DOI":"10.3390\/antiox11101916","volume":"11","author":"A Ullah","year":"2022","unstructured":"Ullah, A. et al. Biogenic selenium nanoparticles and their anticancer effects pertaining to probiotic bacteria\u2014A review. Antioxidants 11, 1916 (2022).","journal-title":"Antioxidants"},{"key":"53359_CR53","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1080\/17435889.2024.2440301","volume":"20","author":"K Dwivedi","year":"2025","unstructured":"Dwivedi, K. et al. Innovative nanocarrier systems for enhanced delivery of phyto-active compounds in cancer therapy. Nanomedicine 20, 91\u2013116 (2025).","journal-title":"Nanomedicine"},{"key":"53359_CR54","doi-asserted-by":"publisher","first-page":"3698","DOI":"10.3390\/cells11223698","volume":"11","author":"M Ra\u0161kov\u00e1","year":"2022","unstructured":"Ra\u0161kov\u00e1, M. et al. The role of IL-6 in cancer cell invasiveness and metastasis\u2014overview and therapeutic opportunities. Cells 11, 3698 (2022).","journal-title":"Cells"},{"key":"53359_CR55","doi-asserted-by":"publisher","first-page":"e70025","DOI":"10.1111\/jpi.70025","volume":"77","author":"AI \u00c1lvarez-L\u00f3pez","year":"2025","unstructured":"\u00c1lvarez-L\u00f3pez, A. I. et al. Melatonin, an Antitumor Necrosis Factor Therapy. J. Pineal Res. 77, e70025 (2025).","journal-title":"J. Pineal Res."},{"key":"53359_CR56","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s12645-022-00123-0","volume":"13","author":"EM Ebrahem","year":"2022","unstructured":"Ebrahem, E. M., Sayed, G. H., Gad, G. N., Anwer, K. E. & Selim, A. A. Histopathology, pharmacokinetics and estimation of interleukin-6 levels of Moringa oleifera leaves extract-functionalized selenium nanoparticles against rats induced hepatocellular carcinoma. Cancer Nanotechnol. 13, 14 (2022).","journal-title":"Cancer Nanotechnol"},{"key":"53359_CR57","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/bs.apcsb.2022.11.008","volume":"135","author":"M D\u2019costa","year":"2023","unstructured":"D\u2019costa, M. et al. P. CDK regulators\u2014Cell cycle progression or apoptosis\u2014Scenarios in normal cells and cancerous cells. Adv. Protein Chem. Struct. Biol. 135, 125\u2013177 (2023).","journal-title":"Adv. Protein Chem. Struct. Biol."},{"key":"53359_CR58","doi-asserted-by":"publisher","first-page":"1633","DOI":"10.1002\/bab.2233","volume":"69","author":"M Asadi","year":"2022","unstructured":"Asadi, M. et al. Caspase-3: structure, function, and biotechnological aspects. Biotechnol. Appl. Biochem. 69, 1633\u20131645 (2022).","journal-title":"Biotechnol. Appl. Biochem."},{"key":"53359_CR59","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1038\/cdd.2014.216","volume":"22","author":"S Shalini","year":"2015","unstructured":"Shalini, S., Dorstyn, L., Dawar, S. & Kumar, S. Old, new and emerging functions of caspases. Cell. Death Differ. 22, 526\u2013539 (2015).","journal-title":"Cell. Death Differ."},{"key":"53359_CR60","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1111\/j.1600-079X.2012.00973.x","volume":"53","author":"J Wang","year":"2012","unstructured":"Wang, J. et al. Simultaneous modulation of COX-2, p300, Akt, and Apaf\u20101 signaling by melatonin to inhibit proliferation and induce apoptosis in breast cancer cells. J. Pineal Res. 53, 77\u201390 (2012).","journal-title":"J. Pineal Res."},{"key":"53359_CR61","doi-asserted-by":"publisher","first-page":"121708","DOI":"10.1016\/j.lfs.2023.121708","volume":"324","author":"BLV de Godoy","year":"2023","unstructured":"de Godoy, B. L. V. et al. Synergistic actions of Alpelisib and Melatonin in breast cancer cell lines with PIK3CA gene mutation. Life Sci. 324, 121708 (2023).","journal-title":"Life Sci."},{"key":"53359_CR62","doi-asserted-by":"publisher","first-page":"6641","DOI":"10.3390\/ijms23126641","volume":"23","author":"EG Varlamova","year":"2022","unstructured":"Varlamova, E. G., Goltyaev, M. V., Simakin, A. V., Gudkov, S. V. & Turovsky, E. A. Comparative analysis of the cytotoxic effect of a complex of selenium nanoparticles doped with sorafenib,naked selenium nanoparticles, and sorafenib on human hepatocyte carcinoma HepG2 cells. Int. J. Mol. Sci. 23, 6641 (2022).","journal-title":"Int. J. Mol. Sci."},{"key":"53359_CR63","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1007\/s12022-023-09755-3","volume":"34","author":"S La Rosa","year":"2023","unstructured":"La Rosa, S. Diagnostic, prognostic, and predictive role of Ki67 proliferative index in neuroendocrine and endocrine neoplasms: past, present, and future. Endocr. Pathol. 34, 79\u201397 (2023).","journal-title":"Endocr. Pathol."},{"key":"53359_CR64","doi-asserted-by":"publisher","first-page":"259","DOI":"10.2217\/nnm-2022-0198","volume":"18","author":"M Shahidi","year":"2023","unstructured":"Shahidi, M. et al. Using chitosan-stabilized, hyaluronic acid-modified selenium nanoparticles to deliver CD44-targeted PLK1 siRNAs for treating bladder cancer. Nanomedicine 18, 259\u2013277 (2023).","journal-title":"Nanomedicine"},{"key":"53359_CR65","doi-asserted-by":"publisher","first-page":"e08837","DOI":"10.1016\/j.heliyon.2022.e08837","volume":"8","author":"OA Ammar","year":"2022","unstructured":"Ammar, O. A., El-Missiry, M. A., Othman, A. I. & Amer, M. E. Melatonin is a potential oncostatic agent to inhibit HepG2 cell proliferation through multiple pathways. Heliyon 8, e08837 (2022).","journal-title":"Heliyon"},{"key":"53359_CR66","doi-asserted-by":"publisher","first-page":"838","DOI":"10.3390\/cells12060838","volume":"12","author":"M Markowska","year":"2023","unstructured":"Markowska, M., Niemczyk, S. & Romejko, K. Melatonin treatment in kidney diseases. Cells 12, 838 (2023).","journal-title":"Cells"},{"key":"53359_CR67","doi-asserted-by":"publisher","first-page":"749","DOI":"10.3390\/foods11050749","volume":"11","author":"Y Qiu","year":"2022","unstructured":"Qiu, Y. et al. Effects of selenium nanoparticles on preventing patulin-induced liver, kidney and gastrointestinal damage. Foods 11, 749 (2022).","journal-title":"Foods"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-53359-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-53359-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-53359-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T09:02:41Z","timestamp":1779786161000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-53359-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,26]]},"references-count":67,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["53359"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-53359-w","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,26]]},"assertion":[{"value":"29 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This study was performed in line with the principles of the Mansoura University Animal Care and Use Committee (MU-ACAU). Approval was granted by the Ethics Committee of Mansoura University (code number: SC. PhD.22.09.2. R 1).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}}],"article-number":"16264"}}