{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:18:49Z","timestamp":1786976329306,"version":"build-2736575974"},"reference-count":55,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T00:00:00Z","timestamp":1748390400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Advanced Biology"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Non\u2010small cell lung cancer (NSCLC) remains a major cause of cancer\u2010related mortality. This study investigates the cytotoxic effects of\n                    <jats:italic>Euphorbia rigida<\/jats:italic>\n                    extract on A549 NSCLC cells and its potential as a therapeutic agent. Cellular morphology was observed microscopically, and cell viability was evaluated using dose\u2010dependent proliferation assays. Apoptosis\u2010related gene expression\u2014including Bax, Bcl\u20102, and Caspase\u20109\u2014was analyzed via quantitative PCR (qPCR). Chromatographic methods identified bioactive flavonoids, and molecular docking assessed their binding to cancer\u2010related proteins. Additionally, absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles were evaluated. The extract induced apoptotic morphological changes such as cell shrinkage and loss of intercellular contact. A dose\u2010dependent reduction in A549 viability was observed, with an IC\n                    <jats:sub>50<\/jats:sub>\n                    of 0.5 mg mL\n                    <jats:sup>\u22121<\/jats:sup>\n                    . Gene expression indicated activation of the intrinsic mitochondrial apoptotic pathway, with increased Bax and Caspase\u20109 and decreased Bcl\u20102 expression. Flow cytometry using Annexin V\u2010allophycocyanin (V\u2010APC) staining revealed selective cytotoxicity: significant apoptosis in A549 cells while preserving viability in BEAS\u20102B normal lung epithelial cells. Identified flavonoids included quercetin, apigenin, and myricetin, which showed strong binding affinities in docking studies. ADMET profiling supported their drug\u2010likeness. These findings highlight\n                    <jats:italic>E. rigida<\/jats:italic>\n                    potential in NSCLC treatment via apoptosis induction and selective cytotoxicity.\n                  <\/jats:p>","DOI":"10.1002\/adbi.202500136","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T03:35:37Z","timestamp":1748403337000},"source":"Crossref","is-referenced-by-count":4,"title":["Flow Cytometry and Gene Expression Modulation by\n                    <i>Euphorbia rigida<\/i>\n                    Methanol Extract in A549 Lung Cancer Cells: Induction of Apoptosis Through Bax, Caspase\u20109, and Bcl\u20102 Pathways"],"prefix":"10.1002","volume":"9","author":[{"given":"Zeynep Bet\u00fcl","family":"Sar\u0131","sequence":"first","affiliation":[{"name":"Faculty of Medicine Department of Basic Medical Sciences Medical Biology Ankara Y\u0131ld\u0131r\u0131m Beyaz\u0131t University  Ankara 06010 T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammed Emin","family":"Sar\u0131","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Department of Medical Biology Necmettin Erbakan University  Konya 42090 T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6045-0183","authenticated-orcid":false,"given":"Erdi Can","family":"Aytar","sequence":"additional","affiliation":[{"name":"Faculty of Agriculture Department of Horticulture Usak University  U\u015fak 64200 T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abidin","family":"G\u00fcmr\u00fck\u00e7\u00fco\u011flu","sequence":"additional","affiliation":[{"name":"Medicinal\u2010Aromatic Plants Application and Research Center Artvin \u00c7oruh University  Artvin 08000 T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emine Incilay","family":"Toruno\u011flu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Department of Medical Biochemistry Necmettin Erbakan University  Konya 42090 T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuba","family":"Ozdemir\u2010Sanci","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Department of Histology and Embriyology Ankara Yildirim Beyazit University  Ankara 06010 T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gamze","family":"Demirel","sequence":"additional","affiliation":[{"name":"Sel\u00e7uk University \u2013 Ak\u015fehir Kadir Yallag\u00f6z School of Health \u2013 Department of Nutrition and Dietetics  Konya 42560 T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alper","family":"Durmaz","sequence":"additional","affiliation":[{"name":"Ali Nihat G\u00f6kyi\u011fit Botanical Garden Application and Research Center Artvin \u00c7oruh University  Artvin 08000 T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,28]]},"reference":[{"key":"e_1_2_8_1_1","first-page":"45","volume":"25","author":"Thandra K. C.","year":"2021","journal-title":"Contemp. Oncol."},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jddst.2025.107023"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.945102"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13092633"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/15287394.2022.2071787"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/15287394.2022.2156956"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/15287394.2023.2233989"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seppur.2023.123713"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10904-021-02162-3"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.4103\/0974-8490.65510"},{"key":"e_1_2_8_11_1","volume-title":"Flora of Turkey and the East Aegean Islands","author":"Davis P.","year":"1982"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25174019"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2016.02.025"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules17055030"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/01635581.2011.608481"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phytochem.2007.01.017"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0367-326X(02)00213-7"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(01)01285-0"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2017.11.031"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2019.01.005"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2020.100712"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.985363"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-023-00629-4"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2012.02.013"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.8157"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s43088-021-00143-6"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23020387"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.03.072"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s42535-023-00621-5"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sajb.2022.08.015"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sciaf.2023.e01943"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eujim.2024.102361"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-024-05972-3"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.56499\/jppres20.916_9.1.13"},{"key":"e_1_2_8_35_1","first-page":"64","volume":"7","author":"Ghout A.","year":"2018","journal-title":"World J. Environ. Biosci."},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1080\/01926230701320337"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867322666150209150639"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/plants10102193"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.4274\/tjps.80299"},{"key":"e_1_2_8_40_1","first-page":"675","volume":"11","author":"Bakshi H.","year":"2010","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11101993"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.15671\/hjbc.519212"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231911746"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.21977"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/9913179"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.14202\/vetworld.2017.869-872"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/181260"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.04.100"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109604"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-017-0179-x"},{"key":"e_1_2_8_51_1","first-page":"1","volume":"17","author":"Aytar E. C.","year":"2024","journal-title":"Food Bioproc. Tech."},{"key":"e_1_2_8_52_1","unstructured":"POWO Euphorbia rigida M.Bieb. | Plants of the World Online | Kew Science https:\/\/powo.science.kew.org\/taxon\/urn:lsid:ipni.org:names:348063\u20101(accessed: October 2024)."},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2024.111895"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.202301645"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21334"}],"container-title":["Advanced Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adbi.202500136","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T07:20:36Z","timestamp":1758266436000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adbi.202500136"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,28]]},"references-count":55,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1002\/adbi.202500136"],"URL":"https:\/\/doi.org\/10.1002\/adbi.202500136","archive":["Portico"],"relation":{},"ISSN":["2701-0198","2701-0198"],"issn-type":[{"value":"2701-0198","type":"print"},{"value":"2701-0198","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,28]]},"article-number":"e00136"}}