{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:53:22Z","timestamp":1791003202655,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T00:00:00Z","timestamp":1785628800000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Food Science &amp;amp; Nutrition"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Lung cancer remains one of the leading causes of cancer\u2010related mortality worldwide, and although Cytarabine (CYT) exhibits anticancer activity, its clinical application is often restricted by dose\u2010dependent toxicity. In this study, we investigated the synergistic anticancer potential of the NCBI\u2010registered probiotic\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Streptococcus thermophilus<\/jats:italic>\n                    <\/jats:styled-content>\n                    Ab.342 SH (GenBank accession no. PX426457) in combination with CYT against human lung adenocarcinoma A549 cells. Following molecular identification of the probiotic isolate, A549 cells were treated with different concentrations of bacterial cell\u2010free supernatant (CFS), CYT, or their combination, while human umbilical vein endothelial cells (HUVECs) were used to evaluate selective cytotoxicity. Cell viability was assessed using the MTT assay, apoptosis\u2010related gene expression was analyzed by qRT\u2010PCR, and apoptotic cell death was confirmed by Annexin V\u2010FITC\/PI flow cytometry. The CFS alone reduced A549 cell viability in a dose\u2010dependent manner without significant cytotoxicity toward HUVECs. CYT monotherapy exhibited an IC\u2085\u2080 of approximately 40\u2009\u03bcg\/mL, whereas combination treatment with\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>S. thermophilus<\/jats:italic>\n                    <\/jats:styled-content>\n                    CFS (OD\u2086\u2080\u2080\u2009=\u20091.2) reduced the IC\u2085\u2080 to 145\u2009ng\/mL, representing an approximately 276\u2010fold dose reduction. Combined treatment significantly upregulated\n                    <jats:italic>PTEN, BAX, CASP3, CASP8, CASP9, P53, P21<\/jats:italic>\n                    , and\n                    <jats:italic>FAS<\/jats:italic>\n                    expression while suppressing\n                    <jats:italic>AKT, mTOR, BCL\u20102<\/jats:italic>\n                    , and\n                    <jats:italic>I\u03baB<\/jats:italic>\n                    , accompanied by a marked increase in apoptotic cells. These findings demonstrate that\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>S. thermophilus<\/jats:italic>\n                    <\/jats:styled-content>\n                    Ab.342 SH markedly enhances the anticancer efficacy of CYT while substantially reducing the required drug dosage, supporting the potential application of probiotic\u2010based adjuvant therapy for safer and more effective lung cancer treatment.\n                  <\/jats:p>","DOI":"10.1002\/fsn3.72187","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T04:55:46Z","timestamp":1785732946000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synergistic Anti\u2010Lung Cancer Effects of Cytarabine and a\n                    <scp>NCBI<\/scp>\n                    \u2010Registered\n                    <i>Streptococcus<\/i>\n                    via Modulation of Apoptotic and Survival Pathways"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6552-5268","authenticated-orcid":false,"given":"Abbas","family":"Asoudeh\u2010Fard","sequence":"first","affiliation":[{"name":"Institute Galil\u00e9e University Sorbonne Paris North  Paris France"},{"name":"Research Center for Pharmaceutical Nanotechnology Tabriz University of Medical Sciences  Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farnood","family":"Afrakhteh","sequence":"additional","affiliation":[{"name":"Department of Microbiology Islamic Azad University, Rasht Branch  Rasht Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahra","family":"Rahimi","sequence":"additional","affiliation":[{"name":"Niko Gene Saba Biotech Company, Rayan Novin Pajohan Company  Shiraz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1779-2692","authenticated-orcid":false,"given":"Rakhshan","family":"Hakimelahi","sequence":"additional","affiliation":[{"name":"Department of Chemistry Shi. C, Islamic Azad University, Shiraz Branch  Shiraz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Bagher","family":"Nazari","sequence":"additional","affiliation":[{"name":"Department of Microbiology Islamic Azad University, Shiraz Branch  Shiraz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad Mehdi","family":"Nemati","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Research Center Shiraz University of Medical Sciences  Shiraz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abbas","family":"Fazlinia","sequence":"additional","affiliation":[{"name":"Department of Chemistry Islamic Azad University, Shiraz Branch  Shiraz Iran"},{"name":"Department of Biology Zand Institute of Higher Education, Rayan Novin Pajohan Company  Shiraz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asghar","family":"Parsaei","sequence":"additional","affiliation":[{"name":"Zand Institute of Higher Education  Shiraz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,2]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-025-04032-1"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12906-024-04730-9"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crbiot.2026.100366"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-025-03034-3"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2025.104050"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-025-02886-z"},{"key":"e_1_2_13_8_1","article-title":"Enhanced Efficacy of Breast cancer Treatment With Etoposide\u2010Graphene Oxide Nanogels: A Novel Nanomedicine Approach","volume":"16","author":"Asoudeh\u2010Fard A.","year":"2025","journal-title":"BioImpacts: BI"},{"issue":"2","key":"e_1_2_13_9_1","first-page":"78","article-title":"Novel Effects of Phycocyanin Extract on the Regulation of Apoptosis Genes in Human Colorectal Cancer Cells","volume":"18","author":"Asoudeh\u2010Fard A.","year":"2024","journal-title":"Iran Journal of Toxicology"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-025-03071-y"},{"key":"e_1_2_13_11_1","volume-title":"Intracellular Pathways Under Stress Conditions and the Role of Antioxidants in Cell Protection","author":"Asoudeh\u2010Fard A.","year":"2025"},{"issue":"4","key":"e_1_2_13_12_1","first-page":"447","article-title":"Isolated \n                     Lactobacillus fermentum\n                   Ab. RS22 From Traditional Dairy Products Inhibits HeLa Cervical cancer Cell Proliferation and Modulates Apoptosis by the PTEN\u2010Akt Pathway","volume":"27","author":"Asoudeh\u2010Fard A.","year":"2024","journal-title":"Iranian Journal of Basic Medical Sciences"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-025-10551-x"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phyplu.2025.100909"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-025-04099-w"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crbiot.2026.100392"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-024-03599-2"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms13061335"},{"issue":"3","key":"e_1_2_13_19_1","first-page":"201","article-title":"Bovine Lactoferrin Ameliorates Antioxidant Esterase Activity and 8\u2010Isoprostane Levels in High\u2010Cholesterol\u2010Diet Fed Rats","volume":"87","author":"Faridvand Y.","year":"2019","journal-title":"International Journal for Vitamin and Nutrition Research"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-024-02005-y"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-025-10626-9"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/foods14173088"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-024-00551-9"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-023-02865-z"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph17040445"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/ot9.0000000000000067"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01856-7"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1080\/21691401.2016.1200059"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/lambio\/ovae084"},{"issue":"3","key":"e_1_2_13_30_1","first-page":"212","article-title":"Calcitriol Modulates Cholesteryl Ester Transfer Protein (CETP) Levels and Lipid Profile in Hypercholesterolemic Male Rabbits: A Pilot Study","volume":"91","author":"Radagdam S.","year":"2019","journal-title":"International Journal for Vitamin and Nutrition Research"},{"key":"e_1_2_13_31_1","first-page":"25","volume-title":"Postbiotics in Metabolic Disorders","author":"Raveendran C.","year":"2026"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.52711\/2349-2996.2024.00016"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26052049"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm14031025"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-11344-9"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/fft2.406"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells13070632"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.2174\/0115748928322627241016120142"}],"container-title":["Food Science &amp; Nutrition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/fsn3.72187","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/fsn3.72187","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/fsn3.72187","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:13:39Z","timestamp":1791000819000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/fsn3.72187"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":37,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/fsn3.72187"],"URL":"https:\/\/doi.org\/10.1002\/fsn3.72187","archive":["Portico"],"relation":{},"ISSN":["2048-7177","2048-7177"],"issn-type":[{"value":"2048-7177","type":"print"},{"value":"2048-7177","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"2025-10-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e72187"}}