{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T06:15:26Z","timestamp":1778134526308,"version":"3.51.4"},"reference-count":78,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Epidemiological studies have demonstrated an inverse correlation between millet-based diets and incidence of cancers of colon and rectum. These findings highlight the potential of millets as functional foods for effective management of cancers. But the experimental evidences supporting these observations remain limited. Among diverse millet varieties, Browntop millet (BTM) has recently been reported to possess potent anti-oxidant and DNA protection properties. Therefore, in the current study we have hypothesized that metabolite rich fractions of browntop millet, particularly the free metabolites extract (BTM-F), exert anticancer effects by targeting key oncogenic pathways that regulate cell proliferation, cell cycle progression, and apoptosis in breast and colorectal cancers. To test this hypothesis, the study aimed to (a) chemically characterize free and bound metabolites (BTM-F and BTM-B) using UPLC-QTOF-MS; (b) evaluate their anticancer efficacy\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    models; (c) delineate their effects on cell cycle regulation and apoptosis, including modulation of caspase-dependent pathways; and(d) investigate the molecular interactions of identified bioactive metabolite with selected oncogenic protein targets using\n                    <jats:italic>in silico<\/jats:italic>\n                    approaches. Results of the study showed that metabolites of browntop millet contained bioactive phenolics and flavonoids which possessed anticancer potential. Both BTM-F and BTM-B demonstrated significant antioxidant activity and reduced viability of breast- and colorectal cancer cells (IC\n                    <jats:sub>50<\/jats:sub>\n                    : 15.36 \u00b1 0.86 to 67.44 \u00b1 7.46\u00a0\u03bcg\/mL). Mechanistically, BTM-F could induce G2\/M cell cycle arrest and promoted apoptosis through increased caspase-3 expression and DNA fragmentation.\n                    <jats:italic>In silico<\/jats:italic>\n                    analyses revealed strong binding of key metabolites-Formononetin-7-O-glucuronide, Naringenin-7-O-\u03b2-D-glucuronide, and Apigenin-7-glucoside to COX-2 and mtALDH-2.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , BTM-F but not BTM-B significantly suppressed EAC tumor growth. In summary, results of this study for the first time, demonstrated the anti-tumor properties of browntop millet free metabolites\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Future studies shall consider BTM-F for testing against patient-derived xenografts and develop functional food-based therapeutic formulation for the better treatment of cancers.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2026.1805287","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T05:41:27Z","timestamp":1778132487000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolites extracted from browntop millet (Urochloa ramosa (L.) T.Q. Nguyen) mitigated the proliferation of breast- and colorectal carcinoma cells in vitro and retarded the EAC tumors in vivo by binding to oncogenic proteins"],"prefix":"10.3389","volume":"17","author":[{"given":"Mahadevaswamy G.","family":"Kuruburu","sequence":"first","affiliation":[{"name":"Center of Excellence in Molecular Biology and Regenerative Medicine (A DST-FIST Supported Center), Department of Biochemistry (A DST-FIST Supported Department), JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER)","place":["Mysuru, Karnataka, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Venugopal R.","family":"Bovilla","sequence":"additional","affiliation":[{"name":"Center of Excellence in Molecular Biology and Regenerative Medicine (A DST-FIST Supported Center), Department of Biochemistry (A DST-FIST Supported Department), JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER)","place":["Mysuru, Karnataka, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rimshia","family":"Naaz","sequence":"additional","affiliation":[{"name":"Center of Excellence in Molecular Biology and Regenerative Medicine (A DST-FIST Supported Center), Department of Biochemistry (A DST-FIST Supported Department), JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER)","place":["Mysuru, Karnataka, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zonunsiami","family":"Leihang","sequence":"additional","affiliation":[{"name":"Center of Excellence in Molecular Biology and Regenerative Medicine (A DST-FIST Supported Center), Department of Biochemistry (A DST-FIST Supported Department), JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER)","place":["Mysuru, Karnataka, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sahana","family":"Shivaramakrishna","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Life Science, JSS Academy of Higher Education & Research (JSS AHER)","place":["Mysuru, Karnataka, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Pramod Kumar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, CSIR-Central Food Technological Research Institute","place":["Mysore, Karnataka, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. V.","family":"Harish Prashanth","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, CSIR-Central Food Technological Research Institute","place":["Mysore, Karnataka, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tousif Ahmed","family":"Hediyal","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research","place":["Mysuru, Karnataka, India"]},{"name":"Centre for Experimental Pharmacology and Toxicology, JSS Academy of Higher Education & Research","place":["Mysuru, Karnataka, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dugganaboyana Guru","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Life Science, JSS Academy of Higher Education & Research (JSS AHER)","place":["Mysuru, Karnataka, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saravana Babu","family":"Chidambaram","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research","place":["Mysuru, Karnataka, India"]},{"name":"Centre for Experimental Pharmacology and Toxicology, JSS Academy of Higher Education & Research","place":["Mysuru, Karnataka, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T Durai Ananda","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, JSS College of Pharmacy","place":["Ooty, Tamil Nadu, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle","family":"Twilley","sequence":"additional","affiliation":[{"name":"Department of Plant and Soil Sciences, Faculty of Natural and Agricultural sciences, University of Pretoria","place":["Pretoria, South Africa"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Namrita","family":"Lall","sequence":"additional","affiliation":[{"name":"Department of Plant and Soil Sciences, Faculty of Natural and Agricultural sciences, University of Pretoria","place":["Pretoria, South Africa"]},{"name":"School of Natural Resources, University of Missouri","place":["Columbia, MO, United States"]},{"name":"Bio-Tech Research and Development Institute, The University of the West Indies","place":["Mona, Jamaica"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Preethi G.","family":"Anantharaju","sequence":"additional","affiliation":[{"name":"Center of Excellence in Molecular Biology and Regenerative Medicine (A DST-FIST Supported Center), Department of Biochemistry (A DST-FIST Supported Department), JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER)","place":["Mysuru, Karnataka, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"SubbaRao V.","family":"Madhunapantula","sequence":"additional","affiliation":[{"name":"Center of Excellence in Molecular Biology and Regenerative Medicine (A DST-FIST Supported Center), Department of Biochemistry (A DST-FIST Supported Department), JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER)","place":["Mysuru, Karnataka, India"]},{"name":"Special Interest Group in Cancer Biology and Cancer Stem Cells (SIG-CBCSC), JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER)","place":["Mysuru, Karnataka, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"221","DOI":"10.3390\/biom10020221","article-title":"Therapeutic potential of plant phenolic acids in the treatment of cancer","volume":"10","author":"Abotaleb","year":"2020","journal-title":"Biomolecules"},{"key":"B2","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1016\/j.joim.2019.09.004","article-title":"Induction of sub-G(0) arrest and apoptosis by seed extract of Moringa peregrina (forssk.) fiori in cervical and prostate cancer cell lines","volume":"17","author":"Abou-Hashem","year":"2019","journal-title":"J. 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