{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:55:21Z","timestamp":1787028921390,"version":"build-2736575974"},"reference-count":158,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Marine-derived natural products are increasingly recognized for their therapeutic potential in cancer and other chronic diseases. Despite significant advances, current cancer treatments remain challenged by toxicity, drug resistance, and limited survival benefits. Natural compounds offer promising alternatives due to their multi-target mechanisms and favorable safety profiles. Among them, Spirulina, a filamentous cyanobacterium, stands out for its rich composition and diverse biological activities. Its anticancer effects involve apoptosis induction via intrinsic and extrinsic pathways, cell cycle arrest at G1\/S or G2\/M phases, inhibition of angiogenesis through the VEGF\/VEGFR2 axis, and suppression of epithelial\u2013mesenchymal transition. These activities are mainly attributed to C-phycocyanin, allophycocyanin, phenolic compounds, and immunomodulatory polysaccharides. Spirulina also exhibits potent immunomodulatory effects by enhancing natural killer cell activity, promoting M1 macrophage polarization, and regulating Th1 and Th17 cytokine responses, highlighting its potential as both an immunotherapeutic and chemoprotective agent. Moreover, preclinical findings suggest it may reduce chemotherapy-associated side effects. However, translation into clinical therapy remains limited by low bioavailability, lack of standardized extracts, and scarce clinical evidence. This review summarizes current mechanistic and immunological insights and highlights the need for optimized formulations, defined dosing strategies, and well-designed clinical trials to validate Spirulina\u2019s potential in cancer treatment.<\/jats:p>","DOI":"10.3390\/medsci14020189","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T10:20:16Z","timestamp":1775816416000},"page":"189","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Spirulina and Its Bioactive Compounds as Multi-Target Anticancer Agents: Mechanisms, Immune Modulation, and Translational Potential"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0020-3775","authenticated-orcid":false,"given":"Rym","family":"Akrout","sequence":"first","affiliation":[{"name":"Laboratory of Genetics Immunology and Human Pathology, Biology Department, Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis 2092, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6033-8597","authenticated-orcid":false,"given":"Khouloud","family":"Ayed","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics Immunology and Human Pathology, Biology Department, Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis 2092, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hela","family":"Mrizak","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics Immunology and Human Pathology, Biology Department, Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis 2092, Tunisia"},{"name":"Pharmacology Unit, School of Pharmacy, Center for Neuroscience, University of Camerino, 62032 Camerino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9369-5689","authenticated-orcid":false,"given":"Ludovic","family":"Leloup","sequence":"additional","affiliation":[{"name":"Facult\u00e9 des Sciences M\u00e9dicales et Param\u00e9dicales, Institut de NeuroPhysiopathologie (INP), UMR 7051, CNRS, Aix Marseille Universit\u00e9, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orace Mathieu","family":"Kenou","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics Immunology and Human Pathology, Biology Department, Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis 2092, Tunisia"},{"name":"Laboratoire de Biologie Int\u00e9grative pour l\u2019Innovation Th\u00e9rapeutique (BioInov), Facult\u00e9 des Sciences et Techniques (FAST), Universit\u00e9 d\u2019Abomey-Calavi, Abomey-Calavi BP 526, Benin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fid\u00e8le","family":"Fassinou","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics Immunology and Human Pathology, Biology Department, Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis 2092, Tunisia"},{"name":"Laboratoire de Biologie Int\u00e9grative pour l\u2019Innovation Th\u00e9rapeutique (BioInov), Facult\u00e9 des Sciences et Techniques (FAST), Universit\u00e9 d\u2019Abomey-Calavi, Abomey-Calavi BP 526, Benin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhouha","family":"Bacha","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics Immunology and Human Pathology, Biology Department, Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis 2092, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahma","family":"Boughriba","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics Immunology and Human Pathology, Biology Department, Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis 2092, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7504-7909","authenticated-orcid":false,"given":"Hanen","family":"Attia","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics Immunology and Human Pathology, Biology Department, Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis 2092, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6509-4210","authenticated-orcid":false,"given":"Herv\u00e9","family":"Kovacic","sequence":"additional","affiliation":[{"name":"Facult\u00e9 des Sciences M\u00e9dicales et Param\u00e9dicales, Institut de NeuroPhysiopathologie (INP), UMR 7051, CNRS, Aix Marseille Universit\u00e9, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1633-9757","authenticated-orcid":false,"given":"Wassim Y.","family":"Almawi","sequence":"additional","affiliation":[{"name":"Faculty of Sciences, University Campus at El-Manar, Tunis 2092, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8507-0451","authenticated-orcid":false,"given":"Asma","family":"Gati","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics Immunology and Human Pathology, Biology Department, Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis 2092, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","first-page":"229","article-title":"Chapter 8\u2014Marine Resource: A Promising Future for Anticancer Drugs","volume":"Volume 40","year":"2013","journal-title":"Studies in Natural Products Chemistry"},{"key":"ref_3","first-page":"1","article-title":"Chemotherapy for Late-Stage Cancer Patients: Meta-Analysis of Complete Response Rates","volume":"4","author":"Abbott","year":"2015","journal-title":"F1000Research"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5574","DOI":"10.1002\/cam4.2474","article-title":"Are 90% of deaths from cancer caused by metastases?","volume":"8","author":"Rogers","year":"2019","journal-title":"Cancer Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Pearce, A., Haas, M., Viney, R., Pearson, S.-A., Haywood, P., Brown, C., and Ward, R. (2017). Incidence and severity of self-reported chemotherapy side effects in routine care: A prospective cohort study. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0184360"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/s41586-019-1730-1","article-title":"A view on drug resistance in cancer","volume":"575","author":"Vasan","year":"2019","journal-title":"Nature"},{"key":"ref_7","unstructured":"(2025, September 17). National Institutes of Health Financial Burden of Cancer Care, Available online: https:\/\/progressreport.cancer.gov\/after\/economic_burden."},{"key":"ref_8","first-page":"100218","article-title":"Semisynthesis: Bridging natural products and novel anticancer therapies","volume":"12","author":"Goel","year":"2024","journal-title":"Eur. J. Med. Chem. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s43141-021-00290-4","article-title":"Promising bioactive compounds from the marine environment and their potential effects on various diseases","volume":"20","author":"Karthikeyan","year":"2022","journal-title":"J. Genet. Eng. Biotechnol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1021\/acs.jcim.8b00125","article-title":"Cheminformatic Insight into the Differences between Terrestrial and Marine Originated Natural Products","volume":"58","author":"Shang","year":"2018","journal-title":"J. Chem. Inf. Model."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Smyrniotopoulos, V., de Andrade Tomaz, A.C., Vanderlei de Souza, M.D., Leit\u00e3o da Cunha, E.V., Kiss, R., Mathieu, V., Ioannou, E., and Roussis, V. (2019). Halogenated Diterpenes with In Vitro Antitumor Activity from the Red Alga Sphaerococcus coronopifolius. Mar. Drugs, 18.","DOI":"10.3390\/md18010029"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Egbewande, F.A., Schwartz, B.D., Duffy, S., Avery, V.M., and Davis, R.A. (2023). Synthesis and Antimalarial Evaluation of Halogenated Analogues of Thiaplakortone A. Mar. Drugs, 21.","DOI":"10.3390\/md21050317"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1124\/jpet.122.527010","article-title":"Marine-Derived Pharmaceuticals in Clinical Trials in 2022","volume":"385","author":"Mayer","year":"2023","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Luna-Nophal, A., D\u00edaz-Castillo, F., Izquierdo-S\u00e1nchez, V., Vel\u00e1zquez-Fern\u00e1ndez, J.B., Orozco-Morales, M., Lara-Mej\u00eda, L., Bern\u00e1ldez-Sarabia, J., S\u00e1nchez-Campos, N., Arrieta, O., and D\u00edaz-Ch\u00e1vez, J. (2025). Preclinical Efficacy and Proteomic Prediction of Molecular Targets for s-cal14.1b and s-cal14.2b Conotoxins with Antitumor Capacity in Xenografts of Malignant Pleural Mesothelioma. Mar. Drugs, 23.","DOI":"10.3390\/md23010032"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Podg\u00f3rska-Kryszczuk, I. (2024). Spirulina\u2014An Invaluable Source of Macro- and Micronutrients with Broad Biological Activity and Application Potential. Molecules, 29.","DOI":"10.3390\/molecules29225387"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"dos Ramos, S.P., B\u00fcrck, M., da Costa, S.F.F., Assis, M., and Braga, A.R.C. (2025). Spirulina as a Key Ingredient in the Evolution of Eco-Friendly Cosmetics. BioTech, 14.","DOI":"10.3390\/biotech14020041"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.biopha.2018.06.116","article-title":"Anticancer effect of the water extract of a commercial Spirulina (Arthrospira platensis) product on the human lung cancer A549 cell line","volume":"106","author":"Czerwonka","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/S1665-2681(19)30891-9","article-title":"Anti-cancer effects of blue-green alga Spirulina platensis, a natural source of bilirubin-like tetrapyrrolic compounds","volume":"13","author":"Vankova","year":"2014","journal-title":"Ann. Hepatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1007\/s10811-025-03496-y","article-title":"Augmentation of the stability of phycocyanin from Arthrospira maxima (Spirulina) by the addition of food preservatives and influence of pH on extracts obtained with different extraction procedures","volume":"37","author":"Tran","year":"2025","journal-title":"J. Appl. Phycol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Fernandes, R., Campos, J., Serra, M., Fidalgo, J., Almeida, H., Casas, A., Toubarro, D., and Barros, A.I.R.N.A. (2023). Exploring the Benefits of Phycocyanin: From Spirulina Cultivation to Its Widespread Applications. Pharmaceuticals, 16.","DOI":"10.3390\/ph16040592"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.2174\/1389557516666161004161411","article-title":"Phycobilins and Phycobiliproteins Used in Food Industry and Medicine","volume":"17","author":"Solymosi","year":"2017","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7803846","DOI":"10.1155\/2016\/7803846","article-title":"Medical Application of Spirulina platensis Derived C-Phycocyanin","volume":"2016","author":"Liu","year":"2016","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e31642","DOI":"10.1016\/j.heliyon.2024.e31642","article-title":"Characterization of C-phycocyanin antioxidant, anti-inflammatory, anti-tumour, and anti-HCoV-229E activities and encapsulation for implementation in an innovative functional yogurt","volume":"10","author":"Soliman","year":"2024","journal-title":"Heliyon"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"102391","DOI":"10.1016\/j.algal.2021.102391","article-title":"Comparison of C-phycocyanin from extremophilic Galdieria sulphuraria and Spirulina platensis on stability and antioxidant capacity","volume":"58","author":"Wan","year":"2021","journal-title":"Algal Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1038\/s42003-021-02767-x","article-title":"Non-conventional octameric structure of C-phycocyanin","volume":"4","author":"Minato","year":"2021","journal-title":"Commun. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s13036-025-00496-x","article-title":"Unraveling the unique bioactivities of highly purified C-phycocyanin and allophycocyanin","volume":"19","author":"Na","year":"2025","journal-title":"J. Biol. Eng."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Chen, H., Qi, H., and Xiong, P. (2022). Phycobiliproteins\u2014A Family of Algae-Derived Biliproteins: Productions, Characterization and Pharmaceutical Potentials. Mar. Drugs, 20.","DOI":"10.3390\/md20070450"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Hassanin, S.O., Hegab, A.M.M., Mekky, R.H., Said, M.A., Khalil, M.G., Hamza, A.A., and Amin, A. (2024). Combining In Vitro, In Vivo, and Network Pharmacology Assays to Identify Targets and Molecular Mechanisms of Spirulina-Derived Biomolecules against Breast Cancer. Mar. Drugs, 22.","DOI":"10.3390\/md22070328"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Stanic-Vucinic, D., Minic, S., Nikolic, M.R., Velickovic, T.C., Stanic-Vucinic, D., Minic, S., Nikolic, M.R., and Velickovic, T.C. (2018). Spirulina Phycobiliproteins as Food Components and Complements. Microalgal Biotechnology, IntechOpen.","DOI":"10.5772\/intechopen.73791"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/nchembio.1555","article-title":"Natural strategies for photosynthetic light harvesting","volume":"10","author":"Croce","year":"2014","journal-title":"Nat. Chem. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.nutres.2020.06.010","article-title":"Update on the bioavailability and chemopreventative mechanisms of dietary chlorophyll derivatives","volume":"81","author":"Hayes","year":"2020","journal-title":"Nutr. Res."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Martins, T., Barros, A.N., Rosa, E., and Antunes, L. (2023). Enhancing Health Benefits through Chlorophylls and Chlorophyll-Rich Agro-Food: A Comprehensive Review. Molecules, 28.","DOI":"10.3390\/molecules28145344"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"022013","DOI":"10.1088\/1742-6596\/1280\/2\/022013","article-title":"Characterization and physicochemical properties of chlorophyll extract from Spirulina sp.","volume":"1280","author":"Munawaroh","year":"2019","journal-title":"J. Phys. Conf. Ser."},{"key":"ref_34","first-page":"34","article-title":"Nutritional and Toxicological Aspects of Spirulina (Arthrospira)","volume":"32","year":"2015","journal-title":"Nutr. Hosp."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"929","DOI":"10.21608\/ejabf.2024.395111","article-title":"Hamed Enhancing Beta-Carotene Synthesis in Spirulina platensis using Molybdenum Disulfide Nanoparticles","volume":"28","author":"Al","year":"2024","journal-title":"Egypt. J. Aquat. Biol. Fish."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Black, H.S., Boehm, F., Edge, R., and Truscott, T.G. (2020). The Benefits and Risks of Certain Dietary Carotenoids that Exhibit both Anti- and Pro-Oxidative Mechanisms\u2014A Comprehensive Review. Antioxidants, 9.","DOI":"10.3390\/antiox9030264"},{"key":"ref_37","first-page":"87","article-title":"Beta-carotene enhances natural killer cell activity in athymic mice","volume":"11","author":"Carlos","year":"1997","journal-title":"In Vivo"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1093\/ajcn\/68.1.164","article-title":"Beta-carotene-induced enhancement of natural killer cell activity in elderly men: An investigation of the role of cytokines","volume":"68","author":"Santos","year":"1998","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1093\/jn\/133.2.381","article-title":"Beta-carotene regulates NF-kappaB DNA-binding activity by a redox mechanism in human leukemia and colon adenocarcinoma cells","volume":"133","author":"Palozza","year":"2003","journal-title":"J. Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"37","DOI":"10.15430\/JCP.2018.23.1.37","article-title":"\u03b2-Carotene Inhibits Activation of NF-\u03baB, Activator Protein-1, and STAT3 and Regulates Abnormal Expression of Some Adipokines in 3T3-L1 Adipocytes","volume":"23","author":"Cho","year":"2018","journal-title":"J. Cancer Prev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"205082","DOI":"10.1155\/2013\/205082","article-title":"Zeaxanthin Induces Apoptosis in Human Uveal Melanoma Cells through Bcl-2 Family Proteins and Intrinsic Apoptosis Pathway","volume":"2013","author":"Bi","year":"2013","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"158652","DOI":"10.1016\/j.bbalip.2020.158652","article-title":"Mechanistic understanding of \u03b2-cryptoxanthin and lycopene in cancer prevention in animal models","volume":"1865","author":"Lim","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1093\/advances\/nmx005","article-title":"Xanthophylls","volume":"9","author":"Thomas","year":"2018","journal-title":"Adv. Nutr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e4785","DOI":"10.55251\/jmbfs.4785","article-title":"Spirulina: A Spotlight on Its Nutraceutical Properties and Food Processing Applications","volume":"12","author":"Priyanka","year":"2023","journal-title":"J. Microbiol. Biotechnol. Food Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e19","DOI":"10.1017\/jns.2012.21","article-title":"Spirulina can increase total-body vitamin A stores of Chinese school-age children as determined by a paired isotope dilution technique","volume":"1","author":"Li","year":"2012","journal-title":"J. Nutr. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1018696","DOI":"10.1080\/23311932.2015.1018696","article-title":"Chemistry, encapsulation, and health benefits of \u03b2-carotene\u2014A review","volume":"1","author":"Gul","year":"2015","journal-title":"Cogent Food Agric."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"104112","DOI":"10.1016\/j.algal.2025.104112","article-title":"Metabolomic changes and enhanced digestibility with algae (Spirulina platensis) derived polysaccharides supplementation in broilers","volume":"90","author":"Pootthachaya","year":"2025","journal-title":"Algal Res."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Wang, N., Qin, J., Chen, Z., Wu, J., and Xiang, W. (2024). Optimization of Ultrasonic-Assisted Extraction, Characterization and Antioxidant and Immunoregulatory Activities of Arthrospira platensis Polysaccharides. Molecules, 29.","DOI":"10.3390\/molecules29194645"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1016\/j.crfs.2022.08.016","article-title":"Structure\u2013immunomodulatory activity relationships of dietary polysaccharides","volume":"5","author":"Chen","year":"2022","journal-title":"Curr. Res. Food Sci."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Panya, A., Wathikthinnakon, M., Thepmalee, C., Chiawpanit, C., Panwong, S., Wutti-in, Y., Vongchan, P., Klangsinsirikul, P., Sattayawat, P., and Pekkoh, J. (2024). Polysaccharide extract of Spirulina sp. increases effector immune-cell killing activities against cholangiocarcinoma. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0312414"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Wu, X., Liu, Z., Liu, Y., Yang, Y., Shi, F., Cheong, K.-L., and Teng, B. (2020). Immunostimulatory Effects of Polysaccharides from Spirulina platensis In Vivo and Vitro and Their Activation Mechanism on RAW246.7 Macrophages. Mar. Drugs, 18.","DOI":"10.3390\/md18110538"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1808","DOI":"10.1016\/j.intimp.2006.08.001","article-title":"Toll-like receptor 2-dependent activation of monocytes by Spirulina polysaccharide and its immune enhancing action in mice","volume":"6","author":"Balachandran","year":"2006","journal-title":"Int. Immunopharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"108355","DOI":"10.1016\/j.isci.2023.108355","article-title":"Herbal supplement Spirulina stimulates inflammatory cytokine production in patients with dermatomyositis in vitro","volume":"26","author":"Bax","year":"2023","journal-title":"iScience"},{"key":"ref_54","first-page":"553","article-title":"Bacterial endotoxin-lipopolysaccharide role in inflammatory diseases: An overview","volume":"28","author":"Arya","year":"2025","journal-title":"Iran. J. Basic. Med. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3354\/meps022121","article-title":"Lipid and lipopolysaccharide constituents of cyanobacterium Spirulina platensis (Cyanophyceae, Nostocales)","volume":"22","author":"Tornabene","year":"1985","journal-title":"Mar. Ecol. Prog. Ser."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"531053","DOI":"10.1093\/ecam\/nen058","article-title":"Spirulina in Clinical Practice: Evidence-Based Human Applications","volume":"2011","author":"Karkos","year":"2011","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1089\/jmf.2016.0119","article-title":"The Potential Role of an Endotoxin Tolerance-Like Mechanism for the Anti-Inflammatory Effect of Spirulina platensis Organic Extract in Macrophages","volume":"20","author":"Pham","year":"2017","journal-title":"J. Med. Food"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"684","DOI":"10.3892\/or.2017.5346","article-title":"Spirulina lipopolysaccharides inhibit tumor growth in a Toll-like receptor 4-dependent manner by altering the cytokine milieu from interleukin-17\/interleukin-23 to interferon-\u03b3","volume":"37","author":"Okuyama","year":"2017","journal-title":"Oncol. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Marjanovi\u0107, B., Benkovi\u0107, M., Jurina, T., Soka\u010d Cvetni\u0107, T., Valinger, D., Gajdo\u0161 Kljusuri\u0107, J., and Jurinjak Tu\u0161ek, A. (2024). Bioactive Compounds from Spirulina spp.\u2014Nutritional Value, Extraction, and Application in Food Industry. Separations, 11.","DOI":"10.3390\/separations11090257"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1590\/fst.23920","article-title":"Antioxidant and anti-diabetic properties of Spirulina platensis produced in Turkey","volume":"41","author":"Guldas","year":"2020","journal-title":"Food Sci. Technol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Ty\u015bkiewicz, K., Konkol, M., and R\u00f3j, E. (2018). The Application of Supercritical Fluid Extraction in Phenolic Compounds Isolation from Natural Plant Materials. Molecules, 23.","DOI":"10.3390\/molecules23102625"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Cosme, P., Rodr\u00edguez, A.B., Espino, J., and Garrido, M. (2020). Plant Phenolics: Bioavailability as a Key Determinant of Their Potential Health-Promoting Applications. Antioxidants, 9.","DOI":"10.3390\/antiox9121263"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"128000","DOI":"10.1016\/j.foodchem.2020.128000","article-title":"Synergistic antioxidant effects of phenolic acids and carotenes on H2O2-induced H9c2 cells: Role of cell membrane transporters","volume":"341","author":"Pan","year":"2021","journal-title":"Food Chem."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Chakraborti, S. (2021). A Detailed Overview of ROS-Modulating Approaches in Cancer Treatment. Handbook of Oxidative Stress in Cancer: Therapeutic Aspects, Springer.","DOI":"10.1007\/978-981-16-1247-3"},{"key":"ref_65","first-page":"580","article-title":"Apoptotic effects of phenolic extract from Spirulina platensis on esophagus cancer cell line SK-GT-4","volume":"17","author":"Aljabery","year":"2023","journal-title":"Oncol. Radiother."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"\u015amieszek, A., Giezek, E., Chrapiec, M., Murat, M., Mucha, A., Michalak, I., and Marycz, K. (2017). The Influence of Spirulina platensis Filtrates on Caco-2 Proliferative Activity and Expression of Apoptosis-Related microRNAs and mRNA. Mar. Drugs, 15.","DOI":"10.3390\/md15030065"},{"key":"ref_67","first-page":"1165","article-title":"Phycocyanin-mediated apoptosis in AK-5 tumor cells involves down-regulation of Bcl-2 and generation of ROS","volume":"2","author":"Pardhasaradhi","year":"2003","journal-title":"Mol. Cancer Ther."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.freeradbiomed.2019.03.006","article-title":"Design and characterization of a novel Arthrospira platensis glutathione oxido-reductase-derived antioxidant peptide GM15 and its potent anti-cancer activity via caspase-9 mediated apoptosis in oral cancer cells","volume":"135","author":"Sannasimuthu","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Kozlov, A.V., Javadov, S., and Sommer, N. (2024). Cellular ROS and Antioxidants: Physiological and Pathological Role. Antioxidants, 13.","DOI":"10.3390\/antiox13050602"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"459","DOI":"10.4103\/epj.epj_352_23","article-title":"Antitumor, antioxidant, and anti-inflammatory activity of spirulina against 7,12-dimethylbenzanthracene-induced mammary cancer","volume":"23","author":"Hamdy","year":"2024","journal-title":"Egypt. Pharm. J."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1038\/s41598-024-82924-4","article-title":"Unveiling the potential anticancer activity of Spirulina maxima extract-nanoemulsion through in vitro and in vivo studies","volume":"15","author":"Hussein","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3887","DOI":"10.32604\/or.2025.070729","article-title":"C-Phycocyanin-Cisplatin Combination Targeting Redox Balance for Enhanced Efficacy Against Glioblastoma Cells","volume":"33","author":"Akrout","year":"2025","journal-title":"Oncol. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1002\/jcb.21707","article-title":"Dysregulation of apoptotic signaling in cancer: Molecular mechanisms and therapeutic opportunities","volume":"104","author":"Plati","year":"2008","journal-title":"J. Cell Biochem."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Mustafa, M., Ahmad, R., Tantry, I.Q., Ahmad, W., Siddiqui, S., Alam, M., Abbas, K., Hassan, M.I., and Habib, S. (2024). Apoptosis: A Comprehensive Overview of Signaling Pathways, Morphological Changes, and Physiological Significance and Therapeutic Implications. Cells, 13.","DOI":"10.3390\/cells13221838"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/sj.cdd.4400476","article-title":"Emerging roles of caspase-3 in apoptosis","volume":"6","author":"Porter","year":"1999","journal-title":"Cell Death Differ."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3416","DOI":"10.7150\/jca.21058","article-title":"Phycocyanin: A Potential Drug for Cancer Treatment","volume":"8","author":"Jiang","year":"2017","journal-title":"J. Cancer"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Ravi, M., Tentu, S., Baskar, G., Rohan Prasad, S., Raghavan, S., Jayaprakash, P., Jeyakanthan, J., Rayala, S.K., and Venkatraman, G. (2015). Molecular mechanism of anti-cancer activity of phycocyanin in triple-negative breast cancer cells. BMC Cancer, 15.","DOI":"10.1186\/s12885-015-1784-x"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.bcp.2004.02.025","article-title":"Molecular mechanisms in C-Phycocyanin induced apoptosis in human chronic myeloid leukemia cell line-K562","volume":"68","author":"Subhashini","year":"2004","journal-title":"Biochem. Pharmacol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"115272","DOI":"10.1016\/j.bmc.2019.115272","article-title":"Molecular mechanism of C-phycocyanin induced apoptosis in LNCaP cells","volume":"28","author":"Kaur","year":"2020","journal-title":"Bioorg. Med. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"103624","DOI":"10.1016\/j.algal.2024.103624","article-title":"Biochemical and molecular docking-based assessment of \u2019s bioactive constituents for their potential application as natural anticancer drug","volume":"82","author":"Khalil","year":"2024","journal-title":"Algal Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s12935-018-0511-5","article-title":"C-Phycocyanin exerts anti-cancer effects via the MAPK signaling pathway in MDA-MB-231 cells","volume":"18","author":"Jiang","year":"2018","journal-title":"Cancer Cell Int."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.biopha.2005.06.012","article-title":"Effects of CD59 on antitumoral activities of phycocyanin from Spirulina platensis","volume":"59","author":"Li","year":"2005","journal-title":"Biomed. Pharmacother."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"409","DOI":"10.21608\/ejchem.2025.350286.11107","article-title":"Immunomodulatory and antioxidant Effects of Spirulina against DMBA-Induced Breast Cancer in Rat Model","volume":"68","author":"Mourad","year":"2025","journal-title":"Egypt. J. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"12205","DOI":"10.3390\/ijms140612205","article-title":"Enhancement of Immune Activation Activities of Spirulina maxima Grown in Deep-Sea Water","volume":"14","author":"Choi","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/s41418-019-0474-7","article-title":"Autophagy in cancer: Moving from understanding mechanism to improving therapy responses in patients","volume":"27","author":"Thorburn","year":"2020","journal-title":"Cell Death Differ."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"105145","DOI":"10.1016\/j.jff.2022.105145","article-title":"Phycocyanin diminishes the viability of non-small cell lung cancer cells via induction of autophagy","volume":"94","author":"Hao","year":"2022","journal-title":"J. Funct. Foods"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"34564","DOI":"10.1038\/srep34564","article-title":"Phycocyanin Inhibits Tumorigenic Potential of Pancreatic Cancer Cells: Role of Apoptosis and Autophagy","volume":"6","author":"Liao","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1186\/s12935-020-01384-8","article-title":"C-phycocyanin inhibits epithelial-to-mesenchymal transition in Caski cells","volume":"20","author":"Ji","year":"2020","journal-title":"Cancer Cell Int."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/1747-1028-1-25","article-title":"Regulation of CDK4","volume":"1","author":"Bockstaele","year":"2006","journal-title":"Cell Div."},{"key":"ref_90","first-page":"101139","article-title":"Study the antioxidant effects of blue-green algae Spirulina extract on ROS and MDA production in human lung cancer cells","volume":"28","author":"Tajvidi","year":"2021","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.gene.2016.03.023","article-title":"Transcriptome analysis of phycocyanin inhibitory effects on SKOV-3 cell proliferation","volume":"585","author":"Ying","year":"2016","journal-title":"Gene"},{"key":"ref_92","first-page":"1295","article-title":"Anti-proliferative effects of C-phycocyanin on a human leukemic cell line and induction of apoptosis via the PI3K\/AKT pathway","volume":"2014","author":"Tantirapan","year":"2014","journal-title":"J. Chem. Pharm. Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"10921","DOI":"10.1021\/acs.jafc.8b03495","article-title":"Phycocyanin Reduces Proliferation of Melanoma Cells through Downregulating GRB2\/ERK Signaling","volume":"66","author":"Hao","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s10456-024-09913-z","article-title":"Navigating tumor angiogenesis: Therapeutic perspectives and myeloid cell regulation mechanism","volume":"27","author":"Yang","year":"2024","journal-title":"Angiogenesis"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1139\/bcb-2014-0016","article-title":"Targeting angiogenic pathway for chemoprevention of experimental colon cancer using C-phycocyanin as cyclooxygenase-2 inhibitor","volume":"92","author":"Saini","year":"2014","journal-title":"Biochem. Cell Biol."},{"key":"ref_96","first-page":"87","article-title":"Spirulina platensis\u2019s phycocyanobilin as an antiangiogenesis by inhibiting VEGFR2-VEGFA pathway in breast cancer: In silico study","volume":"2","author":"Jayanti","year":"2021","journal-title":"JSMARTech J. Smart Bioprospect. Technol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"118827","DOI":"10.1016\/j.lfs.2020.118827","article-title":"Spirulina inhibits hepatocellular carcinoma through activating p53 and apoptosis and suppressing oxidative stress and angiogenesis","volume":"265","author":"Mahmoud","year":"2021","journal-title":"Life Sci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2402","DOI":"10.1111\/jcmm.14922","article-title":"Anti-angiogenic effects of the blue-green alga Arthrospira platensis on pancreatic cancer","volume":"24","author":"Strnad","year":"2020","journal-title":"J. Cell Mol. Med."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Leone, I., Costabile, V., Smaldone, G., Franzese, M., Soricelli, A., and D\u2019Agostino, A. (2025). Arthrospira platensis Attenuates Endothelial Inflammation and Monocyte Activation. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26167844"},{"key":"ref_100","first-page":"1951","article-title":"Inhibitory effects of polysaccharide extract from Spirulina platensis on corneal neovascularization","volume":"15","author":"Yang","year":"2009","journal-title":"Mol. Vis."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"118023","DOI":"10.1016\/j.biopha.2025.118023","article-title":"Targeting VEGF signaling for tumor microenvironment remodeling and metastasis inhibition: Therapeutic strategies and insights","volume":"186","author":"Mahaki","year":"2025","journal-title":"Biomed. Pharmacother."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Chitoran, E., Rotaru, V., Stefan, D.-C., Gullo, G., and Simion, L. (2025). Blocking Tumoral Angiogenesis VEGF\/VEGFR Pathway: Bevacizumab\u201420 Years of Therapeutic Success and Controversy. Cancers, 17.","DOI":"10.3390\/cancers17071126"},{"key":"ref_103","unstructured":"Martin, T.A., Ye, L., Sanders, A.J., Lane, J., and Jiang, W.G. (2013). Cancer Invasion and Metastasis: Molecular and Cellular Perspective. Madame Curie Bioscience Database, Landes Bioscience."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1007\/s10930-017-9707-0","article-title":"The Inhibitory Effect of C-phycocyanin Containing Protein Extract (C-PC Extract) on Human Matrix Metalloproteinases (MMP-2 and MMP-9) in Hepatocellular Cancer Cell Line (HepG2)","volume":"36","author":"Kunte","year":"2017","journal-title":"Protein J."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Hao, S., Yan, Y., Li, S., Zhao, L., Zhang, C., Liu, L., and Wang, C. (2018). The In Vitro Anti-Tumor Activity of Phycocyanin against Non-Small Cell Lung Cancer Cells. Mar. Drugs, 16.","DOI":"10.3390\/md16060178"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1186\/s13045-022-01347-8","article-title":"The molecular mechanisms and therapeutic strategies of EMT in tumor progression and metastasis","volume":"15","author":"Huang","year":"2022","journal-title":"J. Hematol. Oncol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"113219","DOI":"10.1016\/j.biopha.2022.113219","article-title":"Spirulina phycocyanin extract and its active components suppress epithelial-mesenchymal transition process in endometrial cancer via targeting TGF-beta1\/SMAD4 signaling pathway","volume":"152","author":"Chen","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_108","first-page":"210609N773","article-title":"Phycocyanin inhibits pancreatic cancer metastasis via suppressing epithelial-mesenchymal transition and targeting Akt\/\u03b2-catenin pathway","volume":"70","author":"Huang","year":"2021","journal-title":"Neoplasma"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Hao, S., Li, S., Wang, J., Zhao, L., Yan, Y., Wu, T., Zhang, J., and Wang, C. (2019). C-Phycocyanin Suppresses the In Vitro Proliferation and Migration of Non-Small-Cell Lung Cancer Cells through Reduction of RIPK1\/NF-\u03baB Activity. Mar. Drugs, 17.","DOI":"10.3390\/md17060362"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/nrclinonc.2016.217","article-title":"Tumour-associated macrophages as treatment targets in oncology","volume":"14","author":"Mantovani","year":"2017","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"53","DOI":"10.4103\/JMAU.JMAU_68_18","article-title":"Mitogen-Activated Protein Kinase Pathway: A Critical Regulator in Tumor-associated Macrophage Polarization","volume":"7","author":"Neamatallah","year":"2019","journal-title":"J. Microsc. Ultrastruct."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"431","DOI":"10.3177\/jnsv.40.431","article-title":"Enhancement of antibody production in mice by dietary Spirulina platensis","volume":"40","author":"Hayashi","year":"1994","journal-title":"J. Nutr. Sci. Vitaminol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"e70025","DOI":"10.1002\/jex2.70025","article-title":"Characterization of Spirulina-derived extracellular vesicles and their potential as a vaccine adjuvant","volume":"3","author":"Sharifpour","year":"2024","journal-title":"J. Extracell. Biol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"5932","DOI":"10.1038\/onc.2008.267","article-title":"NK cells and cancer immunosurveillance","volume":"27","author":"Waldhauer","year":"2008","journal-title":"Oncogene"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.1055\/s-0030-1250043","article-title":"Enhancement of natural killer cell activity in healthy subjects by Immulina\u00ae, a Spirulina extract enriched for Braun-type lipoproteins","volume":"76","author":"Nielsen","year":"2010","journal-title":"Planta Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1111\/j.1349-7006.2009.01188.x","article-title":"Enhancement of antitumor natural killer cell activation by orally administered Spirulina extract in mice","volume":"100","author":"Akao","year":"2009","journal-title":"Cancer Sci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/S1567-5769(01)00166-7","article-title":"Activation of the human innate immune system by Spirulina: Augmentation of interferon production and NK cytotoxicity by oral administration of hot water extract of Spirulina platensis","volume":"2","author":"Hirahashi","year":"2002","journal-title":"Int. Immunopharmacol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/s41568-025-00832-9","article-title":"Regulatory T cells in the tumour microenvironment","volume":"25","author":"Imianowski","year":"2025","journal-title":"Nat. Rev. Cancer"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1186\/s13046-025-03377-9","article-title":"Tumor-associated macrophages remodel the suppressive tumor immune microenvironment and targeted therapy for immunotherapy","volume":"44","author":"Yang","year":"2025","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/s41577-022-00746-9","article-title":"IL-17 and IL-17-producing cells in protection versus pathology","volume":"23","author":"Mills","year":"2023","journal-title":"Nat. Rev. Immunol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"11056","DOI":"10.1111\/jcmm.15743","article-title":"Molecular mechanism for impaired suppressive function of Tregs in autoimmune diseases: A summary of cell-intrinsic and cell-extrinsic factors","volume":"24","author":"Yang","year":"2020","journal-title":"J. Cell Mol. Med."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Subramaiam, H., Chu, W.-L., Radhakrishnan, A.K., Chakravarthi, S., Selvaduray, K.R., and Kok, Y.-Y. (2021). Evaluating Anticancer and Immunomodulatory Effects of Spirulina (Arthrospira) platensis and Gamma-Tocotrienol Supplementation in a Syngeneic Mouse Model of Breast Cancer. Nutrients, 13.","DOI":"10.3390\/nu13072320"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.21037\/tcr.2019.06.13","article-title":"The efficacy of dietary Spirulina as an adjunct to chemotherapy to improve immune function and reduce myelosuppression in patients with malignant tumors","volume":"8","author":"Ge","year":"2019","journal-title":"Transl. Cancer Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1089\/jmf.2007.564","article-title":"Enhancement of human adaptive immune responses by administration of a high-molecular-weight polysaccharide extract from the cyanobacterium Arthrospira platensis","volume":"11","author":"Walsted","year":"2008","journal-title":"J. Med. Food"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1007\/BF02934440","article-title":"Effect of Spirulina platensis polysaccharide on hematopoietic recovery and related cytokines in mice with transplanted tumor treated by chemotherapy","volume":"8","author":"Liu","year":"2002","journal-title":"Chin. J. Integr. Tradit. West. Med."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"453","DOI":"10.2147\/PPA.S292462","article-title":"Cancer Patients\u2019 Perspectives and Experiences of Chemotherapy-Induced Myelosuppression and Its Impact on Daily Life","volume":"15","author":"Epstein","year":"2021","journal-title":"Patient Prefer. Adherence"},{"key":"ref_127","first-page":"616","article-title":"Effect of polysaccharide from Spirulina platensis on hematopoietic cells proliferation, apoptosis and Bcl-2 expression in mice bearing tumor treated with chemotherapy","volume":"37","author":"Liu","year":"2002","journal-title":"Acta Pharm. Sin."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"115616","DOI":"10.1016\/j.fct.2025.115616","article-title":"Protective effect of Spirulina platensis against testicular toxicity induced by bromoxynil octanoate herbicide through reducing oxidative stress, and inflammation and regulating PPAR-\u03b3\/FOXO1\/NF-\u03baB and Nrf-2\/HO-1 signaling pathways","volume":"204","author":"Elsisi","year":"2025","journal-title":"Food Chem. Toxicol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/S0006-291X(03)00586-2","article-title":"C-Phycocyanin, a selective cyclooxygenase-2 inhibitor, induces apoptosis in lipopolysaccharide-stimulated RAW 264.7 macrophages","volume":"304","author":"Reddy","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.cbi.2010.03.013","article-title":"Protective effect of C-phycocyanin against carbon tetrachloride-induced hepatocyte damage in vitro and in vivo","volume":"185","author":"Ou","year":"2010","journal-title":"Chem. Biol. Interact."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.bionut.2011.12.001","article-title":"Hepatoprotective and antioxidative effects of C-phycocyanin from Arthrospira maxima SAG 25780 in CCl4-induced hepatic damage rats","volume":"2","author":"Nagaraj","year":"2012","journal-title":"Biomed. Prev. Nutr."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.lfs.2018.01.010","article-title":"Spirulina ameliorates methotrexate hepatotoxicity via antioxidant, immune stimulation, and proinflammatory cytokines and apoptotic proteins modulation","volume":"196","author":"Khafaga","year":"2018","journal-title":"Life Sci."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1007\/s43450-023-00470-y","article-title":"Spirulina and Thymoquinone Protect Against Methotrexate-Induced Hepatic Injury in Rats","volume":"34","author":"Behairy","year":"2024","journal-title":"Rev. Bras. Farmacogn."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1007\/s00280-006-0231-8","article-title":"Protection against cisplatin-induced nephrotoxicity by Spirulina in rats","volume":"58","author":"Mohan","year":"2006","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1681\/ASN.2020101455","article-title":"Potential Therapeutic Targets for Cisplatin-Induced Kidney Injury: Lessons from Other Models of AKI and Fibrosis","volume":"32","author":"Sears","year":"2021","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1392.e1","DOI":"10.1016\/j.urology.2012.06.053","article-title":"The protective effects of spirulina in cyclophosphamide induced nephrotoxicity and urotoxicity in rats","volume":"80","author":"Sinanoglu","year":"2012","journal-title":"Urology"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1093\/toxres\/tfab037","article-title":"Protective impact of Spirulina platensis against \u03b3-irradiation and thioacetamide-induced nephrotoxicity in rats mediated by regulation of micro-RNA 1 and micro-RNA 146a","volume":"10","author":"Salem","year":"2021","journal-title":"Toxicol. Res."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"E120124225622","DOI":"10.2174\/0126668629269256231222092721","article-title":"Beneficial Effects of Spirulina on Brain Health: A Systematic Review","volume":"3","author":"Kumar","year":"2025","journal-title":"Curr. Funct. Foods"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/s11064-020-03164-2","article-title":"C-phycocyanin Mitigates Cognitive Impairment in Doxorubicin-Induced Chemobrain: Impact on Neuroinflammation, Oxidative Stress, and Brain Mitochondrial and Synaptic Alterations","volume":"46","author":"Wang","year":"2021","journal-title":"Neurochem. Res."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1007\/s11011-024-01477-7","article-title":"Aqueous extract of Spirulina exerts neuroprotection in an experimental model of Alzheimer sporadic disease in mice induced by Streptozotocin","volume":"40","author":"Tavares","year":"2024","journal-title":"Metab. Brain Dis."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.bbi.2019.08.181","article-title":"Amelioration of neurobehavioral and cognitive abilities of F1 progeny following dietary supplementation with Spirulina to protein malnourished mothers","volume":"85","author":"Sinha","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Koh, E.-J., Seo, Y.-J., Choi, J., Lee, H.Y., Kang, D.-H., Kim, K.-J., and Lee, B.-Y. (2017). Spirulina maxima Extract Prevents Neurotoxicity via Promoting Activation of BDNF\/CREB Signaling Pathways in Neuronal Cells and Mice. Molecules, 22.","DOI":"10.3390\/molecules22081363"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/0278-6915(96)00000-2","article-title":"Effect of Spirulina maxima consumption on reproduction and peri- and postnatal development in rats","volume":"34","author":"Salazar","year":"1996","journal-title":"Food Chem. Toxicol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/S0378-8741(98)00080-4","article-title":"Subchronic toxicity study in mice fed Spirulina maxima","volume":"62","author":"Salazar","year":"1998","journal-title":"J. Ethnopharmacol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"123188","DOI":"10.1016\/j.talanta.2021.123188","article-title":"A new paradigm to search for allergenic proteins in novel foods by integrating proteomics analysis and in silico sequence homology prediction: Focus on spirulina and chlorella microalgae","volume":"240","author":"Bianco","year":"2022","journal-title":"Talanta"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1111\/j.1398-9995.2009.02257.x","article-title":"First case report of anaphylaxis to spirulin: Identification of phycocyanin as responsible allergen","volume":"65","author":"Petrus","year":"2010","journal-title":"Allergy"},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Sochacka, M., K\u00f3zka, B., Kurek, E., and Giebu\u0142towicz, J. (2025). Spirulina and Chlorella Dietary Supplements\u2014Are They a Source Solely of Valuable Nutrients?. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262110468"},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Galinyt\u0117, D., Bal\u010di\u016bnait\u0117-Murzien\u0117, G., Karosien\u0117, J., Morudov, D., Naginien\u0117, R., Baranauskien\u0117, D., \u0160ulinskien\u0117, J., Kudlinskien\u0117, I., Savickas, A., and Savickien\u0117, N. (2023). Determination of Heavy Metal Content: Arsenic, Cadmium, Mercury, and Lead in Cyano-Phycocyanin Isolated from the Cyanobacterial Biomass. Plants, 12.","DOI":"10.3390\/plants12173150"},{"key":"ref_149","first-page":"43","article-title":"Heavy Metals Concentration in Commercially available Spirulina Products","volume":"9","year":"2016","journal-title":"Biosci. Biotechnol. Res. Asia"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1016\/j.jaad.2020.06.037","article-title":"The effects of immunostimulatory herbal supplements on autoimmune skin diseases","volume":"84","author":"Chakka","year":"2021","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s42358-025-00446-7","article-title":"Spirulina ingestion and autoimmune disease onset or flare","volume":"65","author":"Martinez","year":"2025","journal-title":"Adv. Rheumatol."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Mukhopadhyay, C.D. (2015). Engineering Spirulina for Enhanced Medicinal Application. Algal Biorefinery: An Integrated Approach, Springer.","DOI":"10.1007\/978-3-319-22813-6_11"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1111\/ajo.13023","article-title":"Oral complementary medicine use and first-cycle in vitro fertilization\u2014What are the effects on the oocyte, the embryo and the pregnancy rate?","volume":"59","author":"Kieu","year":"2019","journal-title":"Aust. N. Z. J. Obstet. Gynaecol."},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Milia, M., Castangia, I., Corrias, F., Aroffu, M., Casula, M., Manca, M.L., Manconi, M., Bouakline, H., and Angioni, A. (2025). Physicochemical Characteristics of Phospholipid Vesicles for Spirulina-Based Dietary Supplement Delivery. Molecules, 30.","DOI":"10.3390\/molecules30122581"},{"key":"ref_155","first-page":"315","article-title":"Pharmacokinetic profile of Arthrospira maxima-derived phycocyanobilin. Development and application of a novel bioanalytical method","volume":"38","year":"2025","journal-title":"J. Appl. Phycol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"2401172","DOI":"10.1002\/advs.202401172","article-title":"Overcoming Biopotency Barriers: Advanced Oral Delivery Strategies for Enhancing the Efficacy of Bioactive Food Ingredients","volume":"11","author":"Liu","year":"2024","journal-title":"Adv. Sci."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"eabo4160","DOI":"10.1126\/scirobotics.abo4160","article-title":"Gastrointestinal tract drug delivery using algae motors embedded in a degradable capsule","volume":"7","author":"Zhang","year":"2022","journal-title":"Sci. Robot."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1080\/01635589509514407","article-title":"Evaluation of chemoprevention of oral cancer with Spirulina fusiformis","volume":"24","author":"Mathew","year":"1995","journal-title":"Nutr. Cancer"}],"container-title":["Medical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3271\/14\/2\/189\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T04:12:27Z","timestamp":1776917547000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3271\/14\/2\/189"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,10]]},"references-count":158,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["medsci14020189"],"URL":"https:\/\/doi.org\/10.3390\/medsci14020189","relation":{},"ISSN":["2076-3271"],"issn-type":[{"value":"2076-3271","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,10]]}}}