{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T23:57:45Z","timestamp":1785455865746,"version":"3.56.0"},"reference-count":43,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Sphaeranthus amaranthoides<\/jats:italic>\n                    , a lesser\u2010known species of the Asteraceae family, has shown promising medicinal properties, prompting investigation into its cytotoxic and pro\u2010apoptotic effects on human cancer cells. This study evaluated aqueous, methanol, ethyl acetate, and hexane leaf extracts for selective anticancer activity. Normal Vero cells and cancer cell lines AGS (gastric) and HT\u201029 (colorectal) were exposed to Sa\u2010EAE extract, and GC\u2013MS analysis identified key bioactive compounds, including methyl 10,13\u2010dimethyltetradecanoate, 3,7,11,15\u2010tetramethyl\u20102\u2010hexadecen\u20101\u2010ol, and 1,3,5\u2010triazine derivatives. The extract showed selective cytotoxicity against AGS cells while sparing normal Vero cells. Apoptosis was evidenced by mitochondrial\u2010membrane depolarization (\u0394\u03a8m), cytochrome c release, activation of Caspase\u20109 and Caspase\u20103, LDH leakage, and modulation of the Bcl\u20102\/Bax ratio. Apoptotic morphology was confirmed via AO\/EB and PI staining. Flow cytometry revealed G\n                    <jats:sub>0<\/jats:sub>\n                    \/G\n                    <jats:sub>1<\/jats:sub>\n                    cell cycle arrest, with downregulation of Cyclin D1 and CDK4 and upregulation of p21 and p27. These findings indicate that Sa\u2010EAE exerts dual effects of mitochondrial\u2010mediated apoptosis and G\n                    <jats:sub>0<\/jats:sub>\n                    \/G\n                    <jats:sub>1<\/jats:sub>\n                    arrest in gastric cancer cells, with minimal toxicity to normal cells, supporting its potential as a therapeutic candidate for further in\u00a0vivo validation.\n                  <\/jats:p>","DOI":"10.1002\/jat.70026","type":"journal-article","created":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T02:30:15Z","timestamp":1768617015000},"page":"2753-2765","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["GC\u2013MS Metabolite Profiling and Induction of Cell Death by\n                    <i>Sphaeranthus amaranthoides<\/i>\n                    Leaf Extracts"],"prefix":"10.1002","volume":"46","author":[{"given":"Kaviya","family":"Ramalingam","sequence":"first","affiliation":[{"name":"Department of Biotechnology, School of bio and Chemical Engineering Sathyabama Institute of Science and Technology  Chennai Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishnu","family":"Nagarajan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, School of bio and Chemical Engineering Sathyabama Institute of Science and Technology  Chennai Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niranjni","family":"Sekar","sequence":"additional","affiliation":[{"name":"Department of Zoology University of Madras  Chennai Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chermakani\u00a0Panneer","family":"Selvam","sequence":"additional","affiliation":[{"name":"Department of Biochemistry University of Madras  Chennai Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhinesh\u00a0Kumar","family":"Rajendran","sequence":"additional","affiliation":[{"name":"Department of Marine Biotechnology Academy of Maritime Education and Training  Chennai Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arulvasu","family":"Chinnasamy","sequence":"additional","affiliation":[{"name":"Department of Zoology University of Madras  Chennai Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiruthiga","family":"Balakrishnan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, School of bio and Chemical Engineering Sathyabama Institute of Science and Technology  Chennai Tamil Nadu India"},{"name":"Chettinad Health and Research Institute (CHRI) Chettinad Academy of Research and Education (CARE), Chettinad Health City  Chennai Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepakrajasekar","family":"Padmanaban","sequence":"additional","affiliation":[{"name":"Department of Zoology University of Madras  Chennai Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3428-7516","authenticated-orcid":false,"given":"Gracy\u00a0Jenifer","family":"Sahayanathan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, School of bio and Chemical Engineering Sathyabama Institute of Science and Technology  Chennai Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/3079895"},{"issue":"7","key":"e_1_2_12_3_1","first-page":"1485","article-title":"Anti\u2010Cancer Effect of Datura Innoxia P. Mill. Leaf Extract in Vitro Through Induction of Apoptosis in Human Colon Adenocarcinoma and Larynx Cancer Cell Lines","volume":"3","author":"Arulvasu C.","year":"2010","journal-title":"Journal of Pharmacy Research"},{"issue":"4","key":"e_1_2_12_4_1","first-page":"153","article-title":"Comparison of Different Solvents on the Extraction of Melastoma Malabathricum Leaves Using Soxhlet Extraction Method","volume":"8","author":"Awang M. A.","year":"2017","journal-title":"Der Pharmacia Lettre"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.7324\/JAPS.2016.60405"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2021.130229"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1039\/b514294f"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phcgj.2013.09.005"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/01926230701320337"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.18097\/pbmc20135902119"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2024.124316"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3627"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.4103\/0974\u20108490.150544"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.4103\/0974\u20108490.171101"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/607109"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1099320"},{"key":"e_1_2_12_17_1","volume-title":"Phytochemical Methods: A Guide to Modern Techniques of Plant Analysis","author":"Harborne J. B.","year":"1998"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.3109\/01480545.2014.919582"},{"issue":"5","key":"e_1_2_12_19_1","first-page":"206","article-title":"Phytochemical and GC\u2010MS Analysis of Sphaeranthus amaranthoides Burm","volume":"8","author":"Kanimozhi S.","year":"2021","journal-title":"Natural Volatiles and Essential Oils"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.5530\/pres.20251946"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003\u20104819\u201064\u20102\u2010485_2"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2013.04.006"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctarc.2024.100845"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2015.4050"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1039\/C6RA04974E"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022\u20101759(83)90303\u20104"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.5530\/pj.2020.12.86"},{"issue":"1","key":"e_1_2_12_28_1","first-page":"45","article-title":"Apoptosis Dysregulation in Human Gastric Carcinomas: Relationship to Anti\u2010 and pro\u2010Apoptotic Protein Expression","volume":"8","author":"Nasif W. A.","year":"2007","journal-title":"Asian Pacific Journal of Cancer Prevention: APJCP"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13399\u2010023\u201004515\u2010z"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13174363"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2018.4547"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1385\/1\u201059259\u2010811\u20100:301"},{"issue":"4","key":"e_1_2_12_33_1","first-page":"125","article-title":"Screening of Antioxidant, Antimutagenic, Antimicrobial Activities and Phytochemical Studies on Sphaeranthus amaranthoides (Burm)","volume":"1","author":"Prabakaran M.","year":"2011","journal-title":"Asian Journal of Pharmacy and Technology"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/1472\u20106750\u20105\u201012"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.238"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014\u20105793(97)00669\u20108"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055\u20109965.EPI\u201010\u20101264"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.22271\/chemi.2020.v8.i2i.8834"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.5897\/AJB2014.14034"},{"issue":"2","key":"e_1_2_12_40_1","first-page":"27","article-title":"Protective Role of Sphaeranthus amaranthoides on Hepatic Marker Enzymes","volume":"12","author":"Swarnalatha Y. S.","year":"2012","journal-title":"Global Journal of Science Frontier Research: Chemistry"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2952"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.76.9.4350"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology12030412"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2308"}],"container-title":["Journal of Applied Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.70026","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jat.70026","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.70026","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T23:00:36Z","timestamp":1785452436000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jat.70026"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,16]]},"references-count":43,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/jat.70026"],"URL":"https:\/\/doi.org\/10.1002\/jat.70026","archive":["Portico"],"relation":{},"ISSN":["0260-437X","1099-1263"],"issn-type":[{"value":"0260-437X","type":"print"},{"value":"1099-1263","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,16]]},"assertion":[{"value":"2025-06-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}