{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T20:45:27Z","timestamp":1769633127722,"version":"3.49.0"},"reference-count":86,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100017160","name":"Beni Suef University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100017160","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>\n                    <jats:italic>Spirulina platensis<\/jats:italic>\n                    (\n                    <jats:italic>S. platensis<\/jats:italic>\n                    ) is a natural microalgae extract that exerts significant cytotoxic effects against different serious cancerous diseases. Lung cancer is one of the most common and leading causes of death all over the world. The purpose is to investigate the anti-proliferative cytotoxic effects of\n                    <jats:italic>S. Platensis<\/jats:italic>\n                    against the adenocarcinomic human alveolar basal epithelial cells (A549 cell line). Also, molecular docking Analysis and pathway Map were investigated. The viability of the cells was determined\n                    <jats:italic>via<\/jats:italic>\n                    the MTT assay. Moreover the lipid peroxidation, total thiol, the protein concentration of Microtubule-associated tumor suppressor 1 (MTUS1), P16, Kirsten rat sarcoma viral oncogene homolog (K-ras), the epidermal growth factor receptor (EGFr), and the molecular parameters (short stature homeobox 2 (SHOX2), Breast cancer metastasis suppressor 1 (BRMS1), B-cell lymphoma 2 (BCL-2), and Bcl-2-associated X protein (BAX) were assessed. In order to define interaction sites and classes, the current study investigates in detail the interactions between the ligand\n                    <jats:italic>S. platensis<\/jats:italic>\n                    and the Interleukin enhancer-binding factor 3 Receptor (IL-F3) of lung cancer. Covalent bonds, H-bonds, and hydrophobic interactions were observed to form with critical residues on the active site. Covalent bonds are identified in seventeen of the complexes. A correlation was observed between binding affinity and molecular size, branching, polar surface area of up to 199 \u00c52, hydrophilicity, and topological diameter for various bonds. In an effort to enhance pharmaceutical quality control, we utilized\n                    <jats:italic>in silico<\/jats:italic>\n                    methodologies to forecast the ADMET (absorption, distribution, metabolism, excretion, and toxicity) of\n                    <jats:italic>S. platensis<\/jats:italic>\n                    . Results revealed a great anti-proliferative cytotoxic effect with a concentration gradient through decreasing the peroxidation content, and the epigenetic markers, with significant up-regulations of the BRMS1 and BAX. In addition to the kinetic and MAP pathways, docking analysis confirmed that\n                    <jats:italic>S. platensis<\/jats:italic>\n                    binds with the highest affinity to the predicted active sites of the tumor receptor IL-F3, thereby validating its antitumor activity. In conclusion, great suppression in the virulence of lung cancer was reported following treatment with\n                    <jats:italic>S. platensis<\/jats:italic>\n                    , illustrating its suspected mechanism of action, safety profile, kinetic properties, molecular docking results, toxicity, and internal pathways.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-24051-2","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T08:44:46Z","timestamp":1762505086000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["In vitro and in silico analysis of the anti-proliferative effects of Spirulina platensis on A549 lung cancer cells"],"prefix":"10.1038","volume":"15","author":[{"given":"Fatma I.","family":"Abo El-Ela","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marwa A.","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salma I.","family":"El-Samannoudy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walid Hamdy","family":"Hassan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doaa R. I.","family":"Abdel-Gawad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,11,7]]},"reference":[{"key":"24051_CR1","first-page":"12","volume":"74","author":"RL Siegel","year":"2024","unstructured":"Siegel, R. L., Giaquinto, A. N. & Jemal, A. Cancer statistics, 2024. CA Cancer J. Clin. 74, 12\u201349 (2024).","journal-title":"CA Cancer J. Clin."},{"key":"24051_CR2","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1016\/j.biopha.2018.06.116","volume":"106","author":"A Czerwonka","year":"2018","unstructured":"Czerwonka, A. et al. Anticancer effect of the water extract of a commercial Spirulina (Arthrospira platensis) product on the human lung cancer A549 cell line. Biomed. Pharmacother. 106, 292\u2013302 (2018).","journal-title":"Biomed. Pharmacother"},{"key":"24051_CR3","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1016\/S0025-6196(11)60735-0","volume":"83","author":"JR Molina","year":"2008","unstructured":"Molina, J. R., Yang, P., Cassivi, S. D., Schild, S. E. & Adjei, A. A. Non-small cell lung cancer: Epidemiology, risk factors, treatment, and survivorship. Mayo Clin. Proc. 83, 584\u2013594 (2008).","journal-title":"Mayo Clin. Proc."},{"key":"24051_CR4","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/j.currproblcancer.2017.07.002","volume":"41","author":"N Akhtar","year":"2017","unstructured":"Akhtar, N. & Bansal, J. G. Risk factors of lung cancer in nonsmoker. Curr. Probl. Cancer. 41, 328\u2013339 (2017).","journal-title":"Curr. Probl. Cancer"},{"key":"24051_CR5","unstructured":"WHO report on cancer. (2020)."},{"key":"24051_CR6","doi-asserted-by":"crossref","unstructured":"Baylin, S. B. The cancer epigenome: Its origins, contributions to tumorigenesis, and translational implications. Proc. Am. Thorac. Soc. 9, 64\u201365 (2012).","DOI":"10.1513\/pats.201201-001MS"},{"key":"24051_CR7","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/carcin\/bgp220","volume":"31","author":"S Sharma","year":"2009","unstructured":"Sharma, S., Kelly, T. K. & Jones, P. A. Epigenetics in cancer. Carcinogenesis 31, 27\u201336 (2009).","journal-title":"Carcinogenesis"},{"key":"24051_CR8","first-page":"2","volume":"2017","author":"DM Howell","year":"2017","unstructured":"Howell, D. M. et al. Self management interventions for breathlessness in adult cancer patients. Cochrane Database Syst. Rev. 2017, 2\u20135 (2017).","journal-title":"Cochrane Database Syst. Rev."},{"key":"24051_CR9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-019-52915-x","volume":"9","author":"A Levitsky","year":"2019","unstructured":"Levitsky, A. et al. Early symptoms and sensations as predictors of lung cancer: a machine learning multivariate model. Sci. Rep. 9, 1\u201311 (2019).","journal-title":"Sci. Rep."},{"key":"24051_CR10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/life10100223","volume":"10","author":"M Adnan","year":"2020","unstructured":"Adnan, M. et al. Kenaf (Hibiscus cannabinus L.) leaves and seed as a potential source of the bioactive compounds: effects of various extraction solvents on biological properties. Life 10, 1\u201316 (2020).","journal-title":"Life"},{"key":"24051_CR11","doi-asserted-by":"crossref","unstructured":"Oun, R., Moussa, Y. E., Wheate, N. J. & Correction The side effects of platinum-based chemotherapy drugs: A review for chemists (Dalton Transactions 47 (6645\u20136653) DOI: 10.1039\/C8DT00838H). Dalt. Trans. 47, 7848 (2018). (2018).","DOI":"10.1039\/C8DT00838H"},{"key":"24051_CR12","first-page":"1","volume":"13","author":"MY Huang","year":"2018","unstructured":"Huang, M. Y., Zhang, L., Le, Ding, J. & Lu, J. J. Anticancer drug discovery from Chinese medicinal herbs. Chin. Med. (United Kingdom). 13, 1\u20139 (2018).","journal-title":"Chin. Med. (United Kingdom)"},{"key":"24051_CR13","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.procbio.2010.09.004","volume":"46","author":"S Malik","year":"2011","unstructured":"Malik, S. et al. Production of the anticancer drug taxol in taxus baccata suspension cultures: A review. Process. Biochem. 46, 23\u201334 (2011).","journal-title":"Process. Biochem."},{"key":"24051_CR14","doi-asserted-by":"crossref","unstructured":"Aggarwal, B. B. & Harikumar, K. B. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int. J. Biochem. Cell. Biol. 41 (2009).","DOI":"10.1016\/j.biocel.2008.06.010"},{"issue":"9","key":"24051_CR15","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1080\/17425255.2019.1650914","volume":"15","author":"AB Kunnumakkara","year":"2019","unstructured":"Kunnumakkara, A. B. et al. Is Curcumin bioavailability a problem in humans: lessons from clinical trials. Expert Opin. Drug Metab. Toxicol. 15 (9), 705\u2013733 (2019).","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"24051_CR16","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1021\/acs.jnatprod.5b01055","volume":"79","author":"DJ Newman","year":"2016","unstructured":"Newman, D. J. & Cragg, G. M. Natural products as sources of new drugs from 1981 to 2014. J. Nat. Prod. 79, 629\u2013661 (2016).","journal-title":"J. Nat. Prod."},{"key":"24051_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/md15080237","volume":"15","author":"D Nawrocka","year":"2017","unstructured":"Nawrocka, D., Kornicka, K., \u015amieszek, A. & Marycz, K. Spirulina platensis improves mitochondrial function impaired by elevated oxidative stress in adipose-derived mesenchymal stromal cells (ASCs) and intestinal epithelial cells (IECs), and enhances insulin sensitivity in equine metabolic syndrome (EMS) horse. Mar. Drugs. 15, 1\u201328 (2017).","journal-title":"Mar. Drugs"},{"key":"24051_CR18","doi-asserted-by":"publisher","first-page":"92","DOI":"10.7150\/jca.27462","volume":"10","author":"L Jiang","year":"2019","unstructured":"Jiang, L. et al. Molecular mechanism of anti-cancer activity of the nano-drug C-PC\/CMC-CD59sp NPs in cervical cancer. J. Cancer. 10, 92\u2013104 (2019).","journal-title":"J. Cancer"},{"key":"24051_CR19","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.ejphar.2015.01.009","volume":"749","author":"B Li","year":"2015","unstructured":"Li, B. et al. The synergistic antitumor effects of all-trans retinoic acid and C-phycocyanin on the lung cancer A549 cells in vitro and in vivo. Eur. J. Pharmacol. 749, 107\u2013114 (2015).","journal-title":"Eur. J. Pharmacol."},{"key":"24051_CR20","doi-asserted-by":"publisher","first-page":"846","DOI":"10.3923\/ijp.2015.846.851","volume":"11","author":"AAA Zaid","year":"2015","unstructured":"Zaid, A. A. A., Hammad, D. M. & Sharaf, E. M. Antioxidant and anticancer activity of Spirulina platensis water extracts. Int. J. Pharmacol. 11, 846\u2013851 (2015).","journal-title":"Int. J. Pharmacol."},{"key":"24051_CR21","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.apjtb.2016.10.011","volume":"7","author":"FY Flores Hernandez","year":"2017","unstructured":"Flores Hernandez, F. Y., Khandual, S. & Ram\u00edrez L\u00f3pez, I. G. Cytotoxic effect of Spirulina platensis extracts on human acute leukemia Kasumi-1 and chronic myelogenous leukemia K-562 cell lines. Asian Pac. J. Trop. Biomed. 7, 14\u201319 (2017).","journal-title":"Asian Pac. J. Trop. Biomed."},{"key":"24051_CR22","first-page":"122","volume":"7","author":"GA Ramzi","year":"2015","unstructured":"Ramzi, G. A., Puneeth, H. R., Madhu, C. S. & Sharada, A. C. Antagonistic effects of combination of flaxseed oil and spirulina platensis oil on their biological properties. Int. J. Pharm. Pharm. Sci. 7, 122\u2013127 (2015).","journal-title":"Int. J. Pharm. Pharm. Sci."},{"key":"24051_CR23","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1093\/abbs\/gmp104","volume":"42","author":"B Li","year":"2010","unstructured":"Li, B., Chu, X., Gao, M. & Li, W. Apoptotic mechanism of MCF-7 breast cells in vivo and in vitro induced by photodynamic therapy with C-phycocyanin. Acta Biochim. Biophys. Sin (Shanghai). 42, 80\u201389 (2010).","journal-title":"Acta Biochim. Biophys. Sin (Shanghai)"},{"key":"24051_CR24","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1590\/S1516-89132014005000018","volume":"57","author":"EG Gardeva","year":"2014","unstructured":"Gardeva, E. G. et al. Antitumor activity of C-phycocyanin from arthronema Africanum (Cyanophyceae). Brazilian Arch. Biol. Technol. 57, 675\u2013684 (2014).","journal-title":"Brazilian Arch. Biol. Technol."},{"key":"24051_CR25","unstructured":"Guiry, M. D. & Guiry, G. M. AlgaeBase. World-Wide. Electron. Publ. Natl. Univ. Ireland, Galw. (2022)."},{"key":"24051_CR26","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1128\/MMBR.69.2.292-305.2005","volume":"69","author":"J Sapp","year":"2005","unstructured":"Sapp, J. The Prokaryote-Eukaryote dichotomy: meanings and mythology. Microbiol. Mol. Biol. Rev. 69, 292\u2013305 (2005).","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"24051_CR27","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1016\/j.clnu.2015.09.007","volume":"35","author":"MC Serban","year":"2016","unstructured":"Serban, M. C. et al. B. M. A systematic review and meta-analysis of the impact of Spirulina supplementation on plasma lipid concentrations. Clin. Nutr. 35, 842\u2013851 (2016).","journal-title":"Clin. Nutr."},{"key":"24051_CR28","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1016\/j.sjbs.2018.01.003","volume":"26","author":"WH Al-Qahtani","year":"2019","unstructured":"Al-Qahtani, W. H. & Binobead, M. A. Anti-inflammatory, antioxidant and antihepatotoxic effects of Spirulina platensis against D-galactosamine induced hepatotoxicity in rats. Saudi J. Biol. Sci. 26, 647\u2013652 (2019).","journal-title":"Saudi J. Biol. Sci."},{"key":"24051_CR29","doi-asserted-by":"crossref","unstructured":"Fradinho, P. et al. Effect of arthrospira platensis (spirulina) incorporation on the rheological and bioactive properties of gluten-free fresh pasta. Algal Res 45, (2020).","DOI":"10.1016\/j.algal.2019.101743"},{"key":"24051_CR30","first-page":"295","volume":"86","author":"J Kom\u00e1rek","year":"2014","unstructured":"Kom\u00e1rek, J., Ka\u0161tovsk\u00fd, J., Mare\u0161, J. & Johansen, J. R. Taxonomic classification of cyanoprokaryotes (cyanobacterial genera) 2014, using a polyphasic approach. Preslia 86, 295\u2013335 (2014).","journal-title":"Preslia"},{"key":"24051_CR31","doi-asserted-by":"crossref","unstructured":"Bashandy, S. A. E., Awdan, E., Ebaid, S. A. & Alhazza, I. M. H. Antioxidant Potential of Spirulina platensis Mitigates Oxidative Stress and Reprotoxicity Induced by Sodium Arsenite in Male Rats. Oxid. Med. Cell. Longev. (2016). (2016).","DOI":"10.1155\/2016\/7174351"},{"key":"24051_CR32","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.2174\/1389557511313080009","volume":"13","author":"SM Hoseini","year":"2013","unstructured":"Hoseini, S. M. & Khosravi-Darani, K. Nutritional and medical applications of Spirulina microalgae. Mini Rev. Med. Chem. 13, 1231\u20131237 (2013).","journal-title":"Mini Rev. Med. Chem."},{"key":"24051_CR33","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.aquaculture.2006.05.003","volume":"258","author":"H Watanuki","year":"2006","unstructured":"Watanuki, H., Ota, K., Tassakka, A. C. M. A. & Kato, T. Immunostimulant effects of dietary Spirulina platensis on carp, Cyprinus Carpio. Aquaculture 258, 157\u2013163 (2006).","journal-title":"Aquaculture"},{"key":"24051_CR34","first-page":"1677","volume":"10","author":"Z Jin","year":"2018","unstructured":"Jin, Z. et al. Interleukin enhancer binding factor 2 is a prognostic biomarker for breast cancer that also predicts neoadjuvant chemotherapy responses. Am. J. Transl Res. 10, 1677\u20131689 (2018).","journal-title":"Am. J. Transl Res."},{"key":"24051_CR35","doi-asserted-by":"publisher","first-page":"10149","DOI":"10.1007\/s13277-014-2310-5","volume":"35","author":"Q Huang","year":"2014","unstructured":"Huang, Q. et al. Expression of NF45 correlates with malignant grade in gliomas and plays a pivotal role in tumor growth. Tumor Biol. 35, 10149\u201310157 (2014).","journal-title":"Tumor Biol."},{"issue":"4\u20135","key":"24051_CR36","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1007\/s10735-015-9624-5","volume":"46","author":"T Ni","year":"2015","unstructured":"Ni, T. et al. Upregulated expression of ILF2 in non-small cell lung cancer is associated with tumor cell proliferation and poor prognosis. J. Mol. Histol. 46 (4\u20135), 325\u2013335 (2015).","journal-title":"J. Mol. Histol."},{"key":"24051_CR37","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1053\/j.gastro.2013.10.009","volume":"146","author":"V Haselmann","year":"2014","unstructured":"Haselmann, V. et al. Nuclear death receptor trail-r2 inhibits maturation of let-7 and promotes proliferation of pancreatic and other tumor cells. Gastroenterology 146, 278\u2013290 (2014).","journal-title":"Gastroenterology"},{"key":"24051_CR38","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/s11010-015-2535-7","volume":"410","author":"C Wan","year":"2015","unstructured":"Wan, C. et al. NF45 overexpression is associated with poor prognosis and enhanced cell proliferation of pancreatic ductal adenocarcinoma. Mol. Cell. Biochem. 410, 25\u201335 (2015).","journal-title":"Mol. Cell. Biochem."},{"key":"24051_CR39","doi-asserted-by":"publisher","first-page":"5070","DOI":"10.1021\/pr2005204","volume":"10","author":"YY Lee","year":"2011","unstructured":"Lee, Y. Y. et al. Subcellular tissue proteomics of hepatocellular carcinoma for molecular signature discovery. J. Proteome Res. 10, 5070\u20135083 (2011).","journal-title":"J. Proteome Res."},{"key":"24051_CR40","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1136\/ard.45.1.44","volume":"45","author":"JF Koster","year":"1986","unstructured":"Koster, J. F., Biemond, P. & Swaak, A. J. Intra-cellular and extracellular sulphydryl levels in rheumatoid arthritis. Ann. Rheum. Dis. 45, 44\u201346 (1986).","journal-title":"Ann. Rheum. Dis."},{"key":"24051_CR41","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/0009-3084(87)90071-5","volume":"45","author":"K Yagi","year":"1987","unstructured":"Yagi, K. Lipid peroxides and human disease. Chem. Phys. Lipids. 45:, 337\u2013351 (1987).","journal-title":"Chem. Phys. Lipids"},{"key":"24051_CR42","doi-asserted-by":"publisher","first-page":"5569","DOI":"10.2147\/IJN.S208372","volume":"14","author":"GE Ali","year":"2019","unstructured":"Ali, G. E., Ibrahim, M. A., El-Deeb, A. H., Amer, H. & Zaki, S. M. Pulmonary deregulation of expression of miR-155 and two of its putative target genes; PROS1 and TP53INP1 associated with gold nanoparticles (AuNPs) administration in rat. Int. J. Nanomed. 14, 5569\u20135579 (2019).","journal-title":"Int. J. Nanomed."},{"key":"24051_CR43","doi-asserted-by":"publisher","first-page":"109720","DOI":"10.1016\/j.cbi.2021.109720","volume":"351","author":"RE Abdelrahman","year":"2022","unstructured":"Abdelrahman, R. E. et al. Quercetin ameliorates Ochratoxin A-Induced immunotoxicity in broiler chickens by modulation of PI3K\/AKT pathway. Chem. Biol. Interact. 351, 109720 (2022).","journal-title":"Chem. Biol. Interact."},{"key":"24051_CR44","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.bbrc.2009.08.087","volume":"389","author":"JH Ko","year":"2009","unstructured":"Ko, J. H. et al. Cloning of large-conductance Ca2+-activated K\u2009+\u2009channel \u03b1-subunits in mouse cardiomyocytes. Biochem. Biophys. Res. Commun. 389, 74\u201379 (2009).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"24051_CR45","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1042\/BSR20204091","volume":"41","author":"EI Hassanen","year":"2021","unstructured":"Abdel-Gawad, D. R. I. et al. Estimating the in vitro cytotoxicity of the newly emerged zinc oxide (ZnO) doped chromium nanoparticles using the human fetal lung fibroblast cells (WI38 cells). J. Trace. Elem. Med. Biol. 81, 127342. https:\/\/doi.org\/10.1016\/j.jtemb.2023.127342 (2024).","journal-title":"Biosci. Rep."},{"key":"24051_CR46","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s12859-024-05630-y","volume":"25","author":"M Gamal","year":"2024","unstructured":"Gamal, M. & Ibrahim, M. A. Introducing the f0% method: a reliable and accurate approach for qPCR analysis. BMC Bioinform. 25, 17 (2024).","journal-title":"BMC Bioinform."},{"key":"24051_CR47","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s40203-017-0026-0","volume":"5","author":"T Qidwai","year":"2017","unstructured":"Qidwai, T. QSAR modeling, Docking and ADMET studies for exploration of potential anti-malarial compounds against plasmodium falciparum. Silico Pharmacol. 5, 1\u201313 (2017).","journal-title":"Silico Pharmacol."},{"key":"24051_CR48","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1007\/s10534-015-9851-y","volume":"28","author":"P Fonteh","year":"2015","unstructured":"Fonteh, P. et al. Impedance technology reveals correlations between cytotoxicity and lipophilicity of mono and bimetallic phosphine complexes. Biometals 28, 653\u2013667 (2015).","journal-title":"Biometals"},{"issue":"3","key":"24051_CR49","first-page":"227","volume":"51","author":"W Pak","year":"2012","unstructured":"Pak, W. et al. Anti-oxidative and anti-inflammatory effects of spirulina on rat model of non-alcoholic steatohepatitis. J. Clin. Biochem. Nutr. 51 (3), 227\u2013234 (2012).","journal-title":"J. Clin. Biochem. Nutr."},{"key":"24051_CR50","doi-asserted-by":"crossref","unstructured":"Liu, Q., Huang, Y., Zhang, R., Cai, T. & Cai, Y. Medical Application of Spirulina platensis Derived C-Phycocyanin. Evidence-based Complement. Altern. Med. (2016). (2016).","DOI":"10.1155\/2016\/7803846"},{"key":"24051_CR51","doi-asserted-by":"crossref","unstructured":"Li, B. et al. CD59 underlines the antiatherosclerotic effects of c-phycocyanin on mice. Biomed Res. Int. 12\u201314 (2013). (2013).","DOI":"10.1155\/2013\/729413"},{"key":"24051_CR52","doi-asserted-by":"publisher","unstructured":"Chen, T., Wong, Y. S. & Zheng, W. W. I. T. H. D. R. A. W. N. Induction of G1 cell cycle arrest and mitochondria-mediated apoptosis in MCF-7 human breast carcinoma cells by selenium-enriched Spirulina extract. Biomed. Pharmacother. 6389 https:\/\/doi.org\/10.1016\/j.biopha.2009.09.006 (2009).","DOI":"10.1016\/j.biopha.2009.09.006"},{"key":"24051_CR53","first-page":"67","volume":"2","author":"AM Saleh","year":"2011","unstructured":"Saleh, A. M. & Dhar, D. W. Comparative pigment profiles of different Spirulina strains. Res. Biotechnol. 2, 67\u201374 (2011).","journal-title":"Res. Biotechnol."},{"key":"24051_CR54","doi-asserted-by":"publisher","first-page":"903","DOI":"10.3390\/nu2080903","volume":"2","author":"JA Evans","year":"2010","unstructured":"Evans, J. A. & Johnson, E. J. The role of phytonutrients in skin health. Nutrients 2, 903\u2013928 (2010).","journal-title":"Nutrients"},{"key":"24051_CR55","doi-asserted-by":"publisher","first-page":"4849","DOI":"10.3390\/nu5124849","volume":"5","author":"V Shete","year":"2013","unstructured":"Shete, V. & Quadro, L. Mammalian metabolism of \u03b2-carotene: gaps in knowledge. Nutrients 5, 4849\u20134868 (2013).","journal-title":"Nutrients"},{"key":"24051_CR56","first-page":"101139","volume":"28","author":"E Tajvidi","year":"2021","unstructured":"Tajvidi, E. et al. Study the antioxidant effects of blue-green algae Spirulina extract on ROS and MDA production in human lung cancer cells. Biochem. Biophys. Rep. 28, 101139 (2021).","journal-title":"Biochem. Biophys. Rep."},{"key":"24051_CR57","doi-asserted-by":"publisher","first-page":"229","DOI":"10.4103\/2008-322X.170349","volume":"10","author":"R Paduch","year":"2015","unstructured":"Paduch, R. & Wo\u017aniak, A. The effect of lamium album extract on cultivated human corneal epithelial cells (10.014 PRSV-T). J. Ophthalmic Vis. Res. 10, 229\u2013237 (2015).","journal-title":"J. Ophthalmic Vis. Res."},{"key":"24051_CR58","doi-asserted-by":"publisher","unstructured":"Ravi, M., De, S. L. & Azharuddin, S. The beneficial effects of spirulina focusing on its Immunomodulatory and antioxidant properties. Nutr. Diet. Suppl. 73 https:\/\/doi.org\/10.2147\/nds.s9838 (2010).","DOI":"10.2147\/nds.s9838"},{"issue":"2","key":"24051_CR59","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1089\/jmf.2009.1215","volume":"13","author":"MY Kim","year":"2009","unstructured":"Kim, M. Y. et al. R. Spirulina improves antioxidant status by reducing oxidative stress in rabbits fed a high-cholesterol diet. J. Med. Food. 13 (2), 420\u2013426 (2009).","journal-title":"J. Med. Food"},{"key":"24051_CR60","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ph15121561","volume":"15","author":"MAA Orabi","year":"2022","unstructured":"Orabi, M. A. A. et al. Human lung cancer (A549) cell line cytotoxicity and Anti-Leishmania major activity of Carissa Macrocarpa leaves: A study supported by UPLC-ESI-MS\/MS metabolites profiling and molecular Docking. Pharmaceuticals 15, 1\u201319 (2022).","journal-title":"Pharmaceuticals"},{"key":"24051_CR61","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13046-021-02083-6","volume":"40","author":"Y Teng","year":"2021","unstructured":"Teng, Y. et al. SHOX2 cooperates with STAT3 to promote breast cancer metastasis through the transcriptional activation of WASF3. J. Exp. Clin. Cancer Res. 40, 1\u201312 (2021).","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"24051_CR62","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1042\/BSR20170672","volume":"37","author":"LZ Lin","year":"2017","unstructured":"Lin, L. Z. et al. BRMS1 gene expression May be associated with clinico-pathological features of breast cancer. Biosci. Rep. 37, 4\u201313 (2017).","journal-title":"Biosci. Rep."},{"key":"24051_CR63","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1007\/s10555-020-09871-0","volume":"39","author":"R Zimmermann","year":"2020","unstructured":"Zimmermann, R. & Welch, D. R. BRMS1: A multi-functional signaling molecule metastasis. Cancer Metastasis Rev. 39, 755 (2020).","journal-title":"Cancer Metastasis Rev."},{"key":"24051_CR64","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12935-015-0204-2","volume":"15","author":"MH Naseri","year":"2015","unstructured":"Naseri, M. H. et al. Up regulation of Bax and down regulation of Bcl2 during 3-NC mediated apoptosis in human cancer cells. Cancer Cell. Int. 15, 1\u20139 (2015).","journal-title":"Cancer Cell. Int."},{"key":"24051_CR65","doi-asserted-by":"crossref","unstructured":"Smieszek, A. et al. The influence of Spirulina platensis filtrates on caco-2 proliferative activity and expression of apoptosis-related MicroRNAs and mRNA. Mar Drugs 15, (2017).","DOI":"10.3390\/md15030065"},{"key":"24051_CR66","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12935-018-0511-5","volume":"18","author":"L Jiang","year":"2018","unstructured":"Jiang, L. et al. C-Phycocyanin exerts anti-cancer effects via the MAPK signaling pathway in MDA-MB-231 cells. Cancer Cell. Int. 18, 1\u201314 (2018).","journal-title":"Cancer Cell. Int."},{"key":"24051_CR67","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1634\/theoncologist.7-5-451","volume":"7","author":"S Z\u00f6chbauer-M\u00fcller","year":"2002","unstructured":"Z\u00f6chbauer-M\u00fcller, S., Minna, J. D. & Gazdar, A. F. Aberrant DNA methylation in lung cancer: biological and clinical implications. Oncologist 7, 451\u2013457 (2002).","journal-title":"Oncologist"},{"key":"24051_CR68","doi-asserted-by":"publisher","first-page":"3348","DOI":"10.1038\/sj.onc.1204438","volume":"20","author":"C Umbricht","year":"2001","unstructured":"Umbricht, C. et al. Hypermethylation of 14-3-3 \u03c3 (stratifin) is an early event in breast cancer. Oncogene 20, 3348\u20133353 (2001).","journal-title":"Oncogene"},{"key":"24051_CR69","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1054\/bjoc.1999.0980","volume":"82","author":"H Tsuda","year":"2000","unstructured":"Tsuda, H., Yamamoto, K., Inoue, T., Uchiyama, I. & Umesaki, N. The role of p16-cyclin D\/CDK-pRb pathway in the tumorigenesis of endometrioid-type endometrial carcinoma. Br. J. Cancer. 82, 675\u2013682 (2000).","journal-title":"Br. J. Cancer"},{"issue":"16","key":"24051_CR70","first-page":"4366","volume":"60","author":"M Esteller","year":"2000","unstructured":"Esteller, M. et al. Analysis of adenomatous polyposis coli promoter hypermethylation in human cancer. Cancer Res. 60 (16), 4366\u20134371 (2000).","journal-title":"Cancer Res."},{"key":"24051_CR71","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1002\/ijc.24896","volume":"126","author":"L Buckingham","year":"2010","unstructured":"Buckingham, L. et al. PTEN, RASSF1 and DAPK site-specific hypermethylation and outcome in surgically treated stage I and II nonsmall cell lung cancer patients. Int. J. Cancer. 126, 1630\u20131639 (2010).","journal-title":"Int. J. Cancer"},{"key":"24051_CR72","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1007\/s11748-010-0743-3","volume":"59","author":"S Toyooka","year":"2011","unstructured":"Toyooka, S. et al. Molecular oncology of lung cancer. Gen. Thorac. Cardiovasc. Surg. 59, 527\u2013537 (2011).","journal-title":"Gen. Thorac. Cardiovasc. Surg."},{"key":"24051_CR73","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1016\/j.mehy.2005.09.041","volume":"66","author":"X Meng","year":"2006","unstructured":"Meng, X. & Riordan, N. H. Cancer is a functional repair tissue. Med. Hypotheses. 66, 486\u2013490 (2006).","journal-title":"Med. Hypotheses"},{"key":"24051_CR74","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1016\/j.ccr.2011.09.012","volume":"20","author":"HM O\u2019Hagan","year":"2011","unstructured":"O\u2019Hagan, H. M. et al. Oxidative damage targets complexes containing DNA Methyltransferases, SIRT1, and polycomb members to promoter CpG Islands. Cancer Cell. 20, 606\u2013619 (2011).","journal-title":"Cancer Cell."},{"key":"24051_CR75","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12957-022-02702-2","volume":"20","author":"LY Cheng","year":"2022","unstructured":"Cheng, L. Y. et al. MTUS1 is a promising diagnostic and prognostic biomarker for colorectal cancer. World J. Surg. Oncol. 20, 1\u201315 (2022).","journal-title":"World J. Surg. Oncol."},{"issue":"6","key":"24051_CR76","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.3390\/cancers13061245","volume":"13","author":"N Ranjan","year":"2021","unstructured":"Ranjan, N. et al. The tumor suppressor MTUS1\/ATIP1 modulates tumor promotion in glioma: association with epigenetics and DNA repair. Cancers (Basel). 13 (6), 1245 (2021).","journal-title":"Cancers (Basel)"},{"key":"24051_CR77","doi-asserted-by":"crossref","unstructured":"Junan Li#, M. J. & Poi\u00a7 and M.-D. T. The regulatory mechanisms of tumor supressor p16INK4 and relevance to cancer. Biochemistry 50, 5566\u20135582 (2011).","DOI":"10.1021\/bi200642e"},{"key":"24051_CR78","first-page":"1289","volume":"83","author":"Y Jiao","year":"2018","unstructured":"Jiao, Y., Feng, Y. & Wang, X. Regulation of tumor suppressor gene CDKN2A and encoded p16-INK4a protein by covalent modifications. Biochem 83, 1289\u20131298 (2018).","journal-title":"Biochem"},{"key":"24051_CR79","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1038\/nature13898","volume":"517","author":"PMK Westcott","year":"2015","unstructured":"Westcott, P. M. K. et al. The mutational landscapes of genetic and chemical models of Kras-driven lung cancer. Nature 517, 489\u2013492 (2015).","journal-title":"Nature"},{"key":"24051_CR80","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/j.yexcr.2018.12.004","volume":"374","author":"S Parbin","year":"2019","unstructured":"Parbin, S. et al. DNA methylation regulates Microtubule-associated tumor suppressor 1 in human non-small cell lung carcinoma. Exp. Cell. Res. 374, 323\u2013332 (2019).","journal-title":"Exp. Cell. Res."},{"key":"24051_CR81","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1517\/14728222.2011.648617","volume":"16","author":"P Seshacharyulu","year":"2012","unstructured":"Seshacharyulu, P. et al. Targeting the EGFR signaling pathway in cancer therapy. Expert Opin. Ther. Targets. 16, 15\u201331 (2012).","journal-title":"Expert Opin. Ther. Targets"},{"key":"24051_CR82","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/cancers9050052","volume":"9","author":"P Wee","year":"2017","unstructured":"Wee, P. & Wang, Z. Epidermal growth factor receptor cell proliferation signaling pathways. Cancers (Basel). 9, 1\u201345 (2017).","journal-title":"Cancers (Basel)"},{"key":"24051_CR83","first-page":"1","volume":"13","author":"JX Li","year":"2022","unstructured":"Li, J. X. et al. Targeting mutant Kirsten rat sarcoma viral oncogene homolog in Non-Small cell lung cancer: current Difficulties, integrative treatments and future perspectives. Front. Pharmacol. 13, 1\u201317 (2022).","journal-title":"Front. Pharmacol."},{"key":"24051_CR84","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41392-020-00451-w","volume":"6","author":"L Huang","year":"2021","unstructured":"Huang, L., Guo, Z., Wang, F. & Fu, L. KRAS mutation: from undruggable to druggable in cancer. Signal. Transduct. Target. Ther. 6, 1\u201320 (2021).","journal-title":"Signal. Transduct. Target. Ther."},{"key":"24051_CR85","doi-asserted-by":"crossref","unstructured":"Sasaki, T., Hiroki, K. & Yamashita, Y. The role of epidermal growth factor receptor in cancer metastasis and microenvironment. Biomed Res. Int. (2013). (2013).","DOI":"10.1155\/2013\/546318"},{"key":"24051_CR86","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13578-019-0361-4","volume":"9","author":"Z Koveitypour","year":"2019","unstructured":"Koveitypour, Z. et al. Signaling pathways involved in colorectal cancer progression. Cell. Biosci. 9, 1\u201314 (2019).","journal-title":"Cell. Biosci."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-24051-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-24051-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-24051-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T10:02:54Z","timestamp":1762509774000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-24051-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,7]]},"references-count":86,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["24051"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-24051-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,7]]},"assertion":[{"value":"20 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 November 2025","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":"The study was performed in guidance with the rules of the local ethical committee, IACUC, Faculty of Veterinary Medicine, Cairo University, with known approval number (\n                      \n                        Vet CU 03162023594\n                      \n                      ).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}}],"article-number":"39006"}}