{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T06:52:30Z","timestamp":1781679150910,"version":"3.54.5"},"reference-count":84,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"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:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Breast cancer killed 665,684 patients globally in 2022 despite government efforts and conventional therapies. The hydro-ethanolic extract of Acacia seyal, a sub-Saharan African ethnomedicinal plant, showed moderate cytotoxicity, significant anti-migration and in vivo preventive effects against breast cancer cells. The aim of this study was to propose an improved traditional extract and to evaluate its efficacy and potential mechanism of action.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To achieve this, A. seyal hydro-ethanolic extract (ASHE) was fractionated in polyphenol-enriched (ASpo), polysaccharides (ASsu) and residue (ASre) fractions. Fractions along with the crude extract were tested for their ability to inhibit cell growth (MTT) and proliferation (CCK-8). The promising fraction (ASpo) was further investigated on clone formation, caspase-3, wound healing, chemotaxis and cell adhesion to understand its underlying mechanisms of action. Moreover, ASpo at 18.75 and 37.5 mg\/kg,\n                      <jats:italic>p.o<\/jats:italic>\n                      compared to standard drugs (tamoxifen and letrozole) and control (distilled water) were assessed in a 20-week preventive study of DMBA (50 mg\/kg,\n                      <jats:italic>s.c<\/jats:italic>\n                      )-induced breast cancer by considering tumor incidence, tumor volume, organ mass, histopathological, hematological, antioxidant and anti-inflammatory\/immunomodulatory markers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among the 3 fractions, ASpo compared to control, inhibited (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.01) MDA-MB 231 cells growth, proliferation and clone formation at 50 \u03bcg\/mL. It increased caspase-3 and inhibited cell migration and invasion (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.01) with increase (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.01) adherence to collagen and fibronectin.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , comparable to reference drugs, ASpo reduced tumor incidence (50%), and tumor volume from 7827.30 mm3 (adenocarcinoma SBRIII, 10% lymphocytes infiltration) in DMBA to 804.32 mm3 (adenocarcinoma SBRII, 30% lymphocytes infiltration) at 37.5 mg\/kg. It increased femur and thymus\u2019mass, lymphocytes and monocyte levels (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001) in serum, reduced (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001) TNF-\u03b1, IL-6, IL-12, EGF, nitrites levels whereas increased SOD, catalase and major IFN-\u03b3 cytokine (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001). ASpo additionally showed a safety profile on toxicity organs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Overall, ASpo mainly contributed to anti-breast cancer activities of total crude extract and involved immunomodulatory effects to consider with optimized bioactivity to further investigate it as a promising natural and inexpensive alternative to costly and efficient current immunotherapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1772878","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T05:55:43Z","timestamp":1781675743000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Polyphenol-enriched fraction of Acacia seyal Delile (Mimosaceae) inhibits human triple-negative breast cancer cells and exhibits anticancer and immunomodulatory effects in a DMBA-induced breast cancer model"],"prefix":"10.3389","volume":"17","author":[{"given":"Alain Brice","family":"Tueche","sequence":"first","affiliation":[{"name":"Department of Animal Biology and Physiology, Faculty of Science, University of Yaound\u00e9 1","place":["Yaound\u00e9, Cameroon"]},{"name":"Drug Discovery and Smart Molecules Research Laboratory, Department of Chemical Sciences, University of Johannesburg","place":["Johannesburg, South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Hermann Kengne","family":"Kamdem","sequence":"additional","affiliation":[{"name":"Drug Discovery and Smart Molecules Research Laboratory, Department of Chemical Sciences, University of Johannesburg","place":["Johannesburg, South Africa"]},{"name":"Centre for Natural Product Research (CNPR), Department of Chemical Sciences, University of Johannesburg","place":["Johannesburg, South Africa"]},{"name":"Research Centre for Synthesis and Catalysis, Department of Chemical Sciences, University of Johannesburg-Kingsway Campus","place":["Johannesburg, South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan Lembe","family":"Tonga","sequence":"additional","affiliation":[{"name":"Drug Discovery and Smart Molecules Research Laboratory, Department of Chemical Sciences, University of Johannesburg","place":["Johannesburg, South Africa"]},{"name":"Centre for Natural Product Research (CNPR), Department of Chemical Sciences, University of Johannesburg","place":["Johannesburg, South Africa"]},{"name":"Research Centre for Synthesis and Catalysis, Department of Chemical Sciences, University of Johannesburg-Kingsway Campus","place":["Johannesburg, South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin Mpoh","family":"Mmutlane","sequence":"additional","affiliation":[{"name":"Centre for Natural Product Research (CNPR), Department of Chemical Sciences, University of Johannesburg","place":["Johannesburg, South Africa"]},{"name":"Research Centre for Synthesis and Catalysis, Department of Chemical Sciences, University of Johannesburg-Kingsway Campus","place":["Johannesburg, South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek Tantoh","family":"Ndinteh","sequence":"additional","affiliation":[{"name":"Drug Discovery and Smart Molecules Research Laboratory, Department of Chemical Sciences, University of Johannesburg","place":["Johannesburg, South Africa"]},{"name":"Centre for Natural Product Research (CNPR), Department of Chemical Sciences, University of Johannesburg","place":["Johannesburg, South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Zingue","sequence":"additional","affiliation":[{"name":"Centre for Natural Product Research (CNPR), Department of Chemical Sciences, University of Johannesburg","place":["Johannesburg, South Africa"]},{"name":"Department of Pharmacotoxicology and Pharmacokinetics, Faculty of Medicine and Biomedical Sciences, University of Yaound\u00e9 1","place":["Yaound\u00e9, Cameroon"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieudonn\u00e9","family":"Njamen","sequence":"additional","affiliation":[{"name":"Department of Animal Biology and Physiology, Faculty of Science, University of Yaound\u00e9 1","place":["Yaound\u00e9, Cameroon"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"B79","doi-asserted-by":"publisher","first-page":"4575","DOI":"10.3390\/molecules29194575","article-title":"Immunomodulatory Effects of Green Tea Catechins and Their Ring Fission Metabolites in a Tumor Microenvironment Perspective","volume":"29","author":"Andrade","year":"2024","journal-title":"Molecules"},{"key":"B1","first-page":"396","article-title":"Arbres, arbustes et lianes des zones s\u00e8ches d\u2019Afrique de l\u2019Ouest","author":"Arbonnier","year":"2009","journal-title":"Ed. Qu\u00e6; Mus\u00e9um Natl. D\u2019histoire Nat. (MNHN)"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.3390\/molecules27041171","article-title":"A review on the main phytoconstituents, traditional uses, inventions, and patent literature of gum Arabic emphasizing Acacia seyal","volume":"27","author":"Ashour","year":"2022","journal-title":"Molecules"},{"key":"B3","doi-asserted-by":"publisher","first-page":"41","DOI":"10.3390\/biom15010041","article-title":"The metabolism of creatinine and its usefulness to evaluate kidney function and body composition in clinical practice","volume":"15","author":"\u00c1vila","year":"2025","journal-title":"Biomolecules"},{"key":"B4","doi-asserted-by":"publisher","first-page":"113936","DOI":"10.1016\/j.phytochem.2023.113936","article-title":"N-containing phenolic compounds from Periplaneta americana with triple negative breast cancer inhibitory activity","volume":"218","author":"Bai","year":"2024","journal-title":"Phytochemistry"},{"key":"B5","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/S0140-6736(00)04046-0","article-title":"Inflammation and cancer: back to virchow?","volume":"357","author":"Balkwill","year":"2001","journal-title":"Lancet"},{"key":"B6","doi-asserted-by":"publisher","first-page":"110714","DOI":"10.1016\/j.biopha.2020.110714","article-title":"Pleotropic effects of polyphenols in cardiovascular system","volume":"130","author":"Behl","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"B7","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1038\/s41598-023-51021-3","article-title":"N-glycan profiling of tissue samples to aid breast cancer subtyping","volume":"14","author":"Benesova","year":"2024","journal-title":"Sci. Rep."},{"key":"B8","doi-asserted-by":"publisher","first-page":"228","DOI":"10.3390\/cancers17020228","article-title":"Triple-negative breast cancer progression and drug resistance in the context of epithelial-mesenchymal transition","volume":"17","author":"B\u0142aszczak","year":"2025","journal-title":"Cancers (Basel)"},{"key":"B9","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1007\/s10753-016-0477-1","article-title":"Aptamers against Pro- and anti-inflammatory cytokines: a review","volume":"40","author":"Bohstam","year":"2017","journal-title":"Inflammation"},{"key":"B10","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","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":"B11","doi-asserted-by":"publisher","first-page":"4963","DOI":"10.1038\/s41596-021-00615-0","article-title":"Analysis of clonogenic growth in vitro","volume":"16","author":"Brix","year":"2021","journal-title":"Nat. Protocols"},{"key":"B12","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1016\/j.freeradbiomed.2007.04.026","article-title":"Methods to detect nitric oxide and its metabolites in biological samples","volume":"43","author":"Bryan","year":"2007","journal-title":"Free Radic. Biol. Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"13201","DOI":"10.2147\/OTT.S283033","article-title":"Comparative study of lipophilic Statin activity in 2D and 3D in vitro models of human breast cancer cell lines MDA-MB-231 and MCF-7","volume":"13","author":"Bytautaite","year":"2020","journal-title":"Onco Targets Ther."},{"key":"B14","doi-asserted-by":"publisher","first-page":"847","DOI":"10.3389\/fimmu.2018.00847","article-title":"Interferon-Gamma at the crossroads of tumor immune surveillance or evasion","volume":"9","author":"Castro","year":"2018","journal-title":"Front. Immunol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"111865","DOI":"10.1016\/j.cbi.2025.111865","article-title":"Immunomodulatory evaluation of caffeic acid and its quinic acid derivatives using Th1\/Th2 cytokine secretion profiles and principal component analysis","volume":"424","author":"Chang","year":"2025","journal-title":"Chem. Biol. Interact."},{"key":"B16","doi-asserted-by":"publisher","first-page":"015","DOI":"10.4103\/jlp.jlp_124_17","article-title":"Automated hematology analyzers: recent trends and applications","volume":"10","author":"Chhabra","year":"2018","journal-title":"J. Lab. Physicians."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2213","DOI":"10.3390\/antiox11112213","article-title":"Spectrophotometric methods for measurement of antioxidant activity in food and pharmaceuticals","volume":"11","author":"Christodoulou","year":"2022","journal-title":"Antioxidants"},{"key":"B18","doi-asserted-by":"publisher","first-page":"9542","DOI":"10.1021\/jf102590p","article-title":"Inhibition of pro-inflammatory responses and antioxidant capacity of Mexican blackberry (Rubus spp.) extracts","volume":"58","author":"Cuevas-Rodr\u00edguez","year":"2010","journal-title":"J. Agric. Food Chem."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.1080\/10715760400016139","article-title":"Caffeic acid derivatives: in vitro and in vivo anti-inflammatory properties","volume":"38","author":"da Cunha","year":"2004","journal-title":"Free Radic. Res."},{"key":"B20","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3791\/61122","article-title":"Evaluation of oxidative stress in biological samples using the thiobarbituric acid reactive substances assay","volume":"159","author":"De Leon","year":"2020","journal-title":"J. Vis. Exp."},{"key":"B21","doi-asserted-by":"publisher","first-page":"104","DOI":"10.3390\/antiox14010104","article-title":"Role of oxidative stress in the occurrence, development, and treatment of breast cancer","volume":"14","author":"Dong","year":"2025","journal-title":"Antioxidants (Basel)"},{"key":"B22","doi-asserted-by":"publisher","first-page":"10217","DOI":"10.1007\/s11033-022-07885-1","article-title":"The suppressive role of nanoencapsulated chia oil against DMBA-induced breast cancer through oxidative stress repression and tumor genes expression modulation in rats","volume":"49","author":"El Makawy","year":"2022","journal-title":"Mol. Biol. Rep."},{"key":"B80","doi-asserted-by":"publisher","first-page":"2392","DOI":"10.3390\/molecules25102392","article-title":"Evaluation of antioxidant and antibacterial activities, cytotoxicity of Acacia seyal Del bark extracts and isolated compounds","volume":"25","author":"Elmi","year":"2020","journal-title":"Molecules"},{"key":"B81","doi-asserted-by":"publisher","first-page":"218","DOI":"10.22159\/ijpps.2017v9i11.21802","article-title":"A comparative study of chemical composition of Acacia seyal stem, stem wood and stem bark dry distillates used by Sudanese women as cosmetic and medicine","volume":"2017","author":"Eltayeb","year":"2017","journal-title":"Int. J. Pharm. Pharm. Sci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"4143","DOI":"10.3390\/nu16234143","article-title":"Polyphenols as immunomodulators and epigenetic modulators: an analysis of their role in the treatment and prevention of breast cancer","volume":"16","author":"Eren","year":"2024","journal-title":"Nutrients"},{"key":"B24","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1021\/acs.chemrestox.3c00339","article-title":"Cell via cell viability assay changes cellular metabolic characteristics by intervening with glycolysis and pentose phosphate pathway","volume":"37","author":"Fan","year":"2024","journal-title":"Chem. Res. Toxicol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1038\/laban.254","article-title":"Estimation of rat mammary tumor volume using caliper and ultrasonography measurements","volume":"42","author":"Faustino-Rocha","year":"2013","journal-title":"Lab. Anim. (NY)"},{"key":"B26","doi-asserted-by":"publisher","first-page":"116408","DOI":"10.1016\/j.jep.2023.116408","article-title":"Breast cancer cell growth arrest and chemopreventive effects of Passiflora edulis Sims (Passifloraceae) ethanolic leaves extract on a rat model of mammary carcinoma","volume":"311","author":"Fotsing","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1124\/mol.107.039230","article-title":"p53 and ATM\/ATR regulate 7,12-dimethylbenz[a]anthracene-induced immunosuppression","volume":"73","author":"Gao","year":"2008","journal-title":"Mol. Pharmacol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1080\/10408390903584094","article-title":"Effects of flavonoids and other polyphenols on inflammation","volume":"51","author":"Gonz\u00e1lez","year":"2011","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"B29","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.dib.2015.12.012","article-title":"Data supporting the spectrophotometric method for the estimation of catalase activity","volume":"6","author":"Hadwan","year":"2016","journal-title":"Data Brief"},{"key":"B30","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1186\/s13045-024-01649-z","article-title":"Current and future immunotherapy for breast cancer","volume":"17","author":"Heater","year":"2024","journal-title":"J. Hematol. Oncol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"667514","DOI":"10.3389\/fnut.2021.667514","article-title":"In-vitro investigation of polyphenol-rich date (Phoenix dactylifera L.) seed extract bioactivity","volume":"8","author":"Hilary","year":"2021","journal-title":"Front. Nutr."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1090","DOI":"10.1016\/j.jep.2013.12.011","article-title":"Metabonomics study on the hepatoprotective effect of polysaccharides from different preparations of Angelica sinensis","volume":"151","author":"Hua","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"7432797","DOI":"10.1155\/2016\/7432797","article-title":"Oxidative stress and inflammation: what polyphenols can do for us?","volume":"2016","author":"Hussain","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"B33","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1002\/cyto.b.20021","article-title":"Multiplex bead array assays for detection of soluble cytokines: comparisons of sensitivity and quantitative values among kits from multiple manufacturers","volume":"61","author":"Khan","year":"2004","journal-title":"Cytom. B Clin. Cytom."},{"key":"B34","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1016\/j.jfda.2016.05.003","article-title":"Inhibitory mechanism against oxidative stress of caffeic acid","volume":"24","author":"Khan","year":"2016","journal-title":"J. Food Drug Analysis"},{"key":"B35","doi-asserted-by":"publisher","first-page":"3035","DOI":"10.3892\/or.2015.4304","article-title":"Polyphenol mixtures of Euphorbia supina the inhibit invasion and metastasis of highly metastatic breast cancer MDA-MB-231 cells","volume":"34","author":"Ko","year":"2015","journal-title":"Oncol. Rep."},{"key":"B36","doi-asserted-by":"publisher","first-page":"19","DOI":"10.3390\/molecules25081916","article-title":"Polyphenols extracted from Artemisia annua L. exhibit anti-cancer effects on radio-resistant MDA-MB-231 human breast cancer cells by suppressing stem cell phenotype, \u03b2-catenin, and MMP-9","volume":"25","author":"Ko","year":"2020","journal-title":"Molecules"},{"key":"B37","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1158\/0008-5472.CAN-24-1211","article-title":"Distant metastases of breast cancer resemble primary tumors in cancer cell composition but differ in immune cell phenotypes","volume":"85","author":"Kuett","year":"2025","journal-title":"Cancer Res."},{"key":"B38","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1002\/mc.20309","article-title":"Chemoprevention of rat mammary carcinogenesis by Black tea polyphenols: modulation of xenobiotic\u2010metabolizing enzymes, oxidative stress, cell proliferation, apoptosis, and angiogenesis","volume":"46","author":"Kumaraguruparan","year":"2007","journal-title":"Mol. Carcinog."},{"key":"B39","doi-asserted-by":"publisher","first-page":"6625","DOI":"10.1038\/s41598-020-63465-y","article-title":"Determining organ weight toxicity with Bayesian causal models: improving on the analysis of relative organ weights","volume":"10","author":"Lazic","year":"2020","journal-title":"Sci. Rep."},{"key":"B40","doi-asserted-by":"publisher","first-page":"bqaf045","DOI":"10.1210\/endocr\/bqaf045","article-title":"Effects of Endocrine-Disrupting chemicals on adrenal function","volume":"166","author":"Li","year":"2025","journal-title":"Endocrinology"},{"key":"B41","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/j.jfda.2016.01.005","article-title":"Inhibitory effects of polyphenol-enriched extract from Ziyang tea against human breast cancer MCF-7 cells through reactive oxygen species-dependent mitochondria molecular mechanism","volume":"24","author":"Li","year":"2016","journal-title":"J. Food Drug Anal."},{"key":"B42","doi-asserted-by":"publisher","first-page":"415","DOI":"10.3892\/ijo.2019.4821","article-title":"IR-783 inhibits breast cancer cell proliferation and migration by inducing mitochondrial fission","volume":"55","author":"Li","year":"2019","journal-title":"Int. J. Oncol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1021\/jf801826w","article-title":"Fresh apples suppress mammary carcinogenesis and proliferative activity and induce apoptosis in mammary tumors of the Sprague-Dawley rat","volume":"57","author":"Liu","year":"2009","journal-title":"J. Agric. Food Chem."},{"key":"B44","doi-asserted-by":"publisher","first-page":"925","DOI":"10.7150\/ijms.8951","article-title":"Alanine aminotransferase-old biomarker and new concept: a review","volume":"11","author":"Liu","year":"2014","journal-title":"Int. J. Med. Sci."},{"key":"B45","doi-asserted-by":"publisher","first-page":"e17023","DOI":"10.1038\/sigtrans.2017.23","article-title":"NF-\u03baB signaling in inflammation","volume":"2","author":"Liu","year":"2017","journal-title":"Signal Transduct. Target Ther."},{"key":"B46","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1111\/j.1749-6632.1997.tb56895.x","article-title":"Results of three life-span experimental carcinogenicity and anticarcinogenicity studies on tamoxifen in rats","volume":"26","author":"Maltoni","year":"1997","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1727","DOI":"10.3390\/ani11061727","article-title":"Effects of dietary polyphenols from olive mill waste waters on inflammatory and apoptotic effectors in rabbit ovary","volume":"11","author":"Maranesi","year":"2021","journal-title":"Anim. (Basel)"},{"key":"B48","doi-asserted-by":"publisher","first-page":"13045","DOI":"10.1038\/s41598-019-49631-x","article-title":"Annurca apple polyphenol extract selectively kills MDA-MB-231 cells through ROS generation, sustained JNK activation and cell growth and survival inhibition","volume":"9","author":"Martino","year":"2019","journal-title":"Sci. Rep."},{"key":"B49","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1007\/s12291-024-01222-y","article-title":"Anti-tumor effects of polyphenols via targeting cancer driving signaling pathways: a review","volume":"39","author":"Moar","year":"2024","journal-title":"Indian J. Clin. Biochem."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12906-020-03070-8","article-title":"The leaf aqueous extract of Myrianthus arboreus P. Beauv. (Cecropiaceae) improved letrozole-induced polycystic ovarian syndrome associated conditions and infertility in female Wistar rats","volume":"20","author":"Mvondo","year":"2020","journal-title":"BMC Complement. Med. Ther."},{"key":"B51","doi-asserted-by":"publisher","first-page":"200","DOI":"10.3390\/cancers17020200","article-title":"Evaluating the quality of real-world data on adherence to oral endocrine therapy in breast cancer patients: how real is real-world data?","volume":"17","author":"Navarro","year":"2025","journal-title":"Cancers (Basel)"},{"key":"B52","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1002\/tox.24428","article-title":"Anticancer potential of ethanolic extract of Xylopia aethiopica (Dunal) A. Rich (Annonaceae) dried fruits on breast adenocarcinoma: in vitro and in vivo evidences","volume":"40","author":"Nguedia","year":"2024","journal-title":"Environ. Toxicol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"e24410","DOI":"10.1016\/j.heliyon.2024.e24410","article-title":"Duguetia confinis Engl. and Diels (Annonaceae) inhibitory and cytotoxic effects on breast adenocarcinoma growth both in vitro and in vivo","volume":"10","author":"Nkuimi","year":"2024","journal-title":"Heliyon"},{"key":"B54","doi-asserted-by":"publisher","first-page":"1796","DOI":"10.3390\/pharmaceutics15071796","article-title":"Triple negative breast cancer treatment options and limitations: future outlook","volume":"15","author":"Obidiro","year":"2023","journal-title":"Pharmaceutics"},{"key":"B83","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.3390\/molecules25051020","article-title":"Apoptosis induced by (\u2212)-epicatechin in human breast cancer cells is mediated by reactive oxygen species","volume":"25","author":"Pereyra-Vergara","year":"2020","journal-title":"Molecules"},{"key":"B55","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1038\/nprot.2009.223","article-title":"Preparation of the caspase-3\/7 substrate Ac-DEVD-pNA by solution-phase peptide synthesis","volume":"5","author":"Peterson","year":"2010","journal-title":"Nat. Protoc."},{"key":"B56","doi-asserted-by":"publisher","first-page":"574","DOI":"10.22038\/AJP.2019.13475","article-title":"Cytotoxic activity of caffeic acid and gallic acid against MCF-7 human breast cancer cells: an in silico and in vitro study","volume":"9","author":"Rezaei-Seresht","year":"2019","journal-title":"Avicenna J. Phytomed"},{"key":"B57","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1002\/cbf.3884","article-title":"Cytotoxic, antioxidant, and cytoprotective properties of polyphenol\u2010enriched extracts from pecan nutshells in MDA\u2010MB\u2010231 breast cancer cells","volume":"41","author":"Ribas","year":"2023","journal-title":"Cell Biochem. Funct."},{"key":"B58","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1177\/0192623314532036","article-title":"Significance of rat mammary tumors for human risk assessment","volume":"43","author":"Russo","year":"2015","journal-title":"Toxicol. Pathol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1023\/a:1026443305758","article-title":"Atlas and histologic classification of tumors of the rat mammary gland","volume":"5","author":"Russo","year":"2000","journal-title":"J. Mammary Gland. Biol. Neoplasia"},{"key":"B60","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1089\/adt.2024.109","article-title":"Roadmap to cytotoxicity: exploring assays and mechanisms","volume":"23","author":"Shekhawat","year":"2025","journal-title":"Assay. Drug Dev. Technol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"390","DOI":"10.22271\/veterinary.2025.v10.i6f.2362","article-title":"Exploring the effect of DMBA on haematological and biochemical parameters in rats","volume":"10","author":"Shivani","year":"2025","journal-title":"Int. J. Vet. Sci. Anim. Husb."},{"key":"B62","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1186\/s12906-023-04073-x","article-title":"Comparative anticancer effects of Annona muricata Linn (Annonaceae) leaves and fruits on DMBA-induced breast cancer in female rats","volume":"23","author":"Silihe","year":"2023","journal-title":"BMC Complement. Med. Ther."},{"key":"B63","doi-asserted-by":"publisher","first-page":"915","DOI":"10.3390\/ijms26030915","article-title":"Plant polyphenols as heart\u2019s best friends: from health properties, to cellular effects, to molecular mechanisms of action","volume":"26","author":"Stankovic","year":"2025","journal-title":"Int. J. Mol. Sci."},{"key":"B64","doi-asserted-by":"publisher","first-page":"e0285718","DOI":"10.1371\/journal.pone.0285718","article-title":"Utilization of complementary and alternative medicine (CAM) by women with breast cancer or gynecological cancer","volume":"18","author":"St\u00f6cker","year":"2023","journal-title":"PLoS One"},{"key":"B65","doi-asserted-by":"publisher","first-page":"5","DOI":"10.21836\/PEM20230101","article-title":"Comparison of refractometer and biuret reaction as measurement methods for serum total protein concentration in Warmblood foals","volume":"39","author":"Straub","year":"2023","journal-title":"Pferdeheilkunde"},{"key":"B84","doi-asserted-by":"publisher","first-page":"1456730","DOI":"10.3389\/fnut.2024.1456730","article-title":"Polyphenols in health and food processing: antibacterial, anti-inflammatory, and antioxidant insights","volume":"11","author":"Sun","year":"2024","journal-title":"Front. Nutr."},{"key":"B66","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12967-016-0770-7","article-title":"Role of a polyphenol-enriched preparation on chemoprevention of mammary carcinoma through cancer stem cells and inflammatory pathways modulation","volume":"14","author":"Vuong","year":"2016","journal-title":"J. Transl. Med."},{"key":"B67","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1615\/JEnvironPatholToxicolOncol.2021036057","article-title":"Mangiferin inhibits inflammation and cell proliferation, and activates proapoptotic events via NF-\u03baB inhibition in DMBA-induced mammary carcinogenesis in rats","volume":"40","author":"Wang","year":"2021","journal-title":"J. Environ. Pathol. Toxicol. Oncol."},{"key":"B68","doi-asserted-by":"publisher","first-page":"3019","DOI":"10.3390\/nu15133019","article-title":"Dietary plant polysaccharides for cancer prevention: role of immune cells and gut microbiota, challenges and perspectives","volume":"15","author":"Wang","year":"2023","journal-title":"Nutrients"},{"key":"B69","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1016\/j.jff.2017.08.021","article-title":"Nelumbo nucifera leaf polyphenol extract inhibits breast cancer cells metastasis in vitro and in vivo through PKC\u03b1 targeting","volume":"37","author":"Wu","year":"2017","journal-title":"J. Funct. Foods."},{"key":"B70","doi-asserted-by":"publisher","first-page":"117158","DOI":"10.1016\/j.biopha.2024.117158","article-title":"Caffeic acid inhibits the tumorigenicity of triple-negative breast cancer cells through the FOXO1\/FIS pathway","volume":"178","author":"Xie","year":"2024","journal-title":"Biomed. and Pharmacother."},{"key":"B71","doi-asserted-by":"publisher","first-page":"4348","DOI":"10.53730\/ijhs.v6nS6.10278","article-title":"DMBA induced mammary tumor study of Phyto-fabricated sliver nanoparticles from Russelia Equisetiformis flower extract in rat","volume":"6","author":"Yadav","year":"2022","journal-title":"Int. J. Health Sci."},{"key":"B72","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1038\/s41413-020-00111-3","article-title":"Mechanical suppression of breast cancer cell invasion and paracrine signaling to osteoclasts requires nucleo-cytoskeletal connectivity","volume":"8","author":"Yi","year":"2020","journal-title":"Bone Res."},{"key":"B73","doi-asserted-by":"publisher","first-page":"683","DOI":"10.6004\/jnccn.2021.7116","article-title":"Adjuvant hormone therapy\u2013related hot flashes predict treatment discontinuation and worse breast cancer prognosis","volume":"20","author":"Zeng","year":"2022","journal-title":"J. Natl. Compr. Canc Netw."},{"key":"B74","doi-asserted-by":"publisher","first-page":"4021","DOI":"10.1016\/j.biomaterials.2009.04.005","article-title":"Tissue-specific extracellular matrix coatings for the promotion of cell proliferation and maintenance of cell phenotype","volume":"30","author":"Zhang","year":"2009","journal-title":"Biomaterials"},{"key":"B75","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12943-025-02305-x","article-title":"Advances in cancer immunotherapy: historical perspectives, current developments, and future directions","volume":"24","author":"Zhang","year":"2025","journal-title":"Mol. Cancer"},{"key":"B76","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12906-016-1385-5","article-title":"Estrogenic and cytotoxic potentials of compounds isolated from Millettia macrophylla Benth (Fabaceae): towards a better understanding of its underlying mechanisms","volume":"16","author":"Zingue","year":"2016","journal-title":"BMC Complement. Altern. Med."},{"key":"B77","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.jep.2018.05.021","article-title":"The hydro-ethanolic extract of Acacia seyal (Mimosaceae) stem barks induced death in an ER-negative breast cancer cell line by the intrinsic pathway of apoptosis and inhibited cell migration","volume":"223","author":"Zingue","year":"","journal-title":"J. Ethnopharmacol."},{"key":"B78","doi-asserted-by":"publisher","first-page":"2024602","DOI":"10.1155\/2018\/2024602","article-title":"In vitro cytotoxicity and in vivo antimammary tumor effects of the hydroethanolic extract of Acacia seyal (Mimosaceae) stem bark","volume":"2018","author":"Zingue","year":"","journal-title":"Biomed. Res. Int."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1772878\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T05:55:45Z","timestamp":1781675745000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1772878\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,17]]},"references-count":84,"alternative-id":["10.3389\/fphar.2026.1772878"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1772878","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,17]]},"article-number":"1772878"}}