{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T03:04:20Z","timestamp":1793847860984,"version":"4.6.1"},"reference-count":79,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T00:00:00Z","timestamp":1742169600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T00:00:00Z","timestamp":1742169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007414","name":"Qassim University","doi-asserted-by":"publisher","award":["QU-APC-2025"],"award-info":[{"award-number":["QU-APC-2025"]}],"id":[{"id":"10.13039\/501100007414","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007414","name":"Qassim University","doi-asserted-by":"publisher","award":["QU-APC-2025"],"award-info":[{"award-number":["QU-APC-2025"]}],"id":[{"id":"10.13039\/501100007414","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007414","name":"Qassim University","doi-asserted-by":"publisher","award":["QU-APC-2025"],"award-info":[{"award-number":["QU-APC-2025"]}],"id":[{"id":"10.13039\/501100007414","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007414","name":"Qassim University","doi-asserted-by":"publisher","award":["QU-APC-2025"],"award-info":[{"award-number":["QU-APC-2025"]}],"id":[{"id":"10.13039\/501100007414","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Breast cancer is a prominent health issue among oncological diseases in emerging nations. The study sought to assess the significant function of amygdalin as a protective and chemotherapeutical substance in combating this lethal condition, either independently or in conjunction with tamoxifen therapy. Breast cancer in mice was induced by 7,12-Dimethylbenz(a)anthracene (DMBA). Mice were divided into six groups, 15 mice in each group. (i) control group, (ii) carcinogenic group, (iii) tamoxifen-treated group, (iv) Amygdalin-treated group, (v) (Amygdalin\u2009+\u2009tamoxifen) group, (vi) Amygdalin protective group. Results revealed that DMBA-induced breast cancer caused a significant increase in biochemical parameters such as CEA, CA15.3, CA125, PRL, E2, urea, creatinine, ALT, AST, and ALP and a substantial increase in gene expression of TNF-\u03b1 and BcL-2. In contrast, amygdalin administrations alone or in co-administration with tamoxifen could ameliorate breast cancer by declining TNF-\u03b1, BcL-2 and attenuating the biochemical parameters. Amygdalin administrations showed a significant increase in SOD and GPx antioxidants and upregulation of Caspase-3 and P53 in breast tissue. Moreover, flow cytometric analysis revealed that amygdalin administrations were correlated with CD20 and CD44 and promoted the cell cycle and apoptosis in carcinogenic mice. Indeed, the above results were confirmed by the histopathological examinations, which showed that the DMBA group had proliferated microductular carcinoma with marked mononuclear inflammatory cell infiltration, which decreased by the Amygdalin administrations. In conclusion, amygdalin administration may be effective in preventing breast cancer and exhibiting chemotherapeutic properties.<\/jats:p>","DOI":"10.1038\/s41598-025-93620-2","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T09:03:55Z","timestamp":1742202235000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The protective and chemotherapeutical role of amygdalin in induced mammary cancer in experimental mice and upregulation of related genes"],"prefix":"10.1038","volume":"15","author":[{"given":"Afaf D. Abdel","family":"Mageid","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim M.","family":"Abdel-Wadoud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elsayed I.","family":"Salim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thamer","family":"Aljutaily","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan","family":"Barakat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huda","family":"Aljumayi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khadija S.","family":"Radhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sami O.","family":"Almutairi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarek A.","family":"Ebeid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,17]]},"reference":[{"key":"93620_CR1","doi-asserted-by":"publisher","DOI":"10.1200\/EDBK_175617","author":"NL Henry","year":"2017","unstructured":"Henry, N. L., Bedard, P. L. & DeMichele, A. Standard and Genomic Tools for Decision Support in Breast Cancer Treatment. Am. Soc. Clin. Oncol. Educ. https:\/\/doi.org\/10.1200\/EDBK_175617 (2017).","journal-title":"Am. Soc. Clin. Oncol. Educ."},{"key":"93620_CR2","unstructured":"DeSantis, C., Siegel, R. & Jemal, A. Breast cancer facts & figures 2015\u20132016. Am. Cancer Soc. 44 (2015)."},{"key":"93620_CR3","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.1007\/s00204-020-02733-2","volume":"94","author":"A Hartwig","year":"2020","unstructured":"Hartwig, A. et al. Mode of action-based risk assessment of genotoxic carcinogens. Archives Toxicol. 94, 1787\u20131877. https:\/\/doi.org\/10.1007\/s00204-020-02733-2 (2020).","journal-title":"Archives Toxicol."},{"key":"93620_CR4","doi-asserted-by":"publisher","first-page":"222","DOI":"10.5999\/aps.2016.43.2.222","volume":"43","author":"AR Carmichael","year":"2016","unstructured":"Carmichael, A. R. & Mokbel, K. Evolving Trends in Breast Surgery: Oncoplastic to Onco-Aesthetic Surgery. Arch. Plast. Surg. 43, 222\u2013223. https:\/\/doi.org\/10.5999\/aps.2016.43.2.222 (2016).","journal-title":"Arch. Plast. Surg."},{"key":"93620_CR5","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1210\/me.2003-0202","volume":"18","author":"D-Y Wang","year":"2004","unstructured":"Wang, D.-Y., Fulthorpe, R., Liss, S. N. & Edwards, E. A. Identification of estrogen-responsive genes by complementary deoxyribonucleic acid microarray and characterization of a novel early estrogen-induced gene: EEIG1. Mol. Endocrinol. 18, 402\u2013411. https:\/\/doi.org\/10.1210\/me.2003-0202 (2004).","journal-title":"Mol. Endocrinol."},{"key":"93620_CR6","doi-asserted-by":"publisher","first-page":"389","DOI":"10.7326\/0003-4819-89-3-389","volume":"89","author":"RT Dorr","year":"1978","unstructured":"Dorr, R. T. & Paxinos, J. The current status of laetrile. Ann. Intern. Med. 89, 389\u2013397 (1978).","journal-title":"Ann. Intern. Med."},{"key":"93620_CR7","doi-asserted-by":"publisher","first-page":"770","DOI":"10.3109\/09637481003796314","volume":"61","author":"S-M Shim","year":"2010","unstructured":"Shim, S.-M. & Kwon, H. Metabolites of amygdalin under simulated human digestive fluids. Int. J. Food Sci. Nutr. 61, 770\u2013779. https:\/\/doi.org\/10.3109\/09637481003796314 (2010).","journal-title":"Int. J. Food Sci. Nutr."},{"key":"93620_CR8","unstructured":"Orlikova, B., Legrand, N., Panning, J., Dicato, M. & Diederich, M. in Advances in Nutrition and Cancer. (eds Vincenzo Zappia et al.) 123\u2013143 (Springer Berlin Heidelberg)."},{"key":"93620_CR9","doi-asserted-by":"crossref","unstructured":"Orlikova, B., Legrand, N., Panning, J., Dicato, M. & Diederich, M. in Adv. Nutr. Cancer 123\u2013143 (Springer, 2014).","DOI":"10.1007\/978-3-642-38007-5_8"},{"key":"93620_CR10","unstructured":"Barakat, H. in 1st International Electronic Conference on Nutrients - Nutritional and Microbiota Effects on Chronic Disease session Potential nutraceutical effects of nutrients, phytochemicals, and microbiota in chronic metabolic disorders (MDPI, 2020)."},{"key":"93620_CR11","doi-asserted-by":"publisher","first-page":"1514","DOI":"10.3390\/biom12101514","volume":"12","author":"H Barakat","year":"2022","unstructured":"Barakat, H. et al. Amygdalin: a review on its characteristics, antioxidant potential, gastrointestinal microbiota intervention, anticancer therapeutic and mechanisms, toxicity, and encapsulation. Biomolecules 12, 1514 (2022).","journal-title":"Biomolecules"},{"key":"93620_CR12","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1093\/jnci\/63.5.1279","volume":"63","author":"MA Lea","year":"1979","unstructured":"Lea, M. A. & Koch, M. R. Effects of cyanate, thiocyanate, and amygdalin on metabolite uptake in normal and neoplastic tissues of the Rat2. JNCI J. Nat. Cancer Inst. 63, 1279\u20131283. https:\/\/doi.org\/10.1093\/jnci\/63.5.1279 (1979).","journal-title":"JNCI J. Nat. Cancer Inst."},{"key":"93620_CR13","doi-asserted-by":"publisher","first-page":"1597","DOI":"10.1248\/bpb.29.1597","volume":"29","author":"H-K Chang","year":"2006","unstructured":"Chang, H.-K. et al. Amygdalin induces apoptosis through regulation of Bax and Bcl-2 expressions in human DU145 and LNCaP prostate cancer cells. Biol. Pharm. Bull. 29, 1597\u20131602 (2006).","journal-title":"Biol. Pharm. Bull."},{"key":"93620_CR14","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1080\/08923970600815253","volume":"28","author":"J-S Do","year":"2006","unstructured":"Do, J.-S., Hwang, J.-K., Seo, H.-J., Woo, W.-H. & Nam, S.-Y. Antiasthmatic Activity and Selective Inhibition of Type 2 Helper T cell Response by Aqueous Extract of Semen Armeniacae Amarum. Immunopharmacol. Immunotoxicol. 28, 213\u2013225. https:\/\/doi.org\/10.1080\/08923970600815253 (2006).","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"93620_CR15","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1093\/chromsci\/bmt063","volume":"52","author":"X-B Li","year":"2014","unstructured":"Li, X.-B. et al. Determination and pharmacokinetics of amygdalin in rats by LC\u2013MS-MS. J. Chromatogr. Sci. 52, 476\u2013481 (2014).","journal-title":"J. Chromatogr. Sci."},{"key":"93620_CR16","doi-asserted-by":"publisher","first-page":"3","DOI":"10.4103\/0973-1482.139743","volume":"10","author":"Z Song","year":"2014","unstructured":"Song, Z. & Xu, X. Advanced research on anti-tumor effects of amygdalin. Therapeutics is J. Cancer Res. 10, 3 (2014).","journal-title":"Therapeutics is J. Cancer Res."},{"key":"93620_CR17","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1016\/j.carbpol.2012.05.073","volume":"90","author":"C Zhou","year":"2012","unstructured":"Zhou, C. et al. Enhancement of amygdalin activated with \u03b2-D-glucosidase on HepG2 cells proliferation and apoptosis. Carbohydr. Polym. 90, 516\u2013523 (2012).","journal-title":"Carbohydr. Polym."},{"key":"93620_CR18","doi-asserted-by":"crossref","unstructured":"Scherf, K. A. in Handbook of Plant-Based Food and Drinks Design 371\u2013390 (Elsevier, 2024).","DOI":"10.1016\/B978-0-443-16017-2.00028-0"},{"key":"93620_CR19","first-page":"5156","volume":"11","author":"H-J Park","year":"2005","unstructured":"Park, H.-J. et al. Amygdalin inhibits genes related to cell cycle in SNU-C4 human colon cancer cells. World J. Gastroenterol. 11, 5156 (2005).","journal-title":"World J. Gastroenterol."},{"key":"93620_CR20","doi-asserted-by":"publisher","first-page":"43","DOI":"10.3109\/08923973.2012.738688","volume":"35","author":"Y Chen","year":"2013","unstructured":"Chen, Y. et al. Amygdalin induces apoptosis in human cervical cancer cell line HeLa cells. Immunopharmacol. Immunotoxicol. 35, 43\u201351 (2013).","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"93620_CR21","doi-asserted-by":"publisher","DOI":"10.1007\/s13273-021-00163-4","author":"AA Badawy","year":"2021","unstructured":"Badawy, A. A., Othman, R. Q. A. & El-Magd, M. A. Effect of combined therapy with camel milk-derived exosomes, tamoxifen, and hesperidin on breast cancer. Mol. Cell Toxicol. https:\/\/doi.org\/10.1007\/s13273-021-00163-4 (2021).","journal-title":"Mol. Cell Toxicol."},{"key":"93620_CR22","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1002\/pca.2476","volume":"25","author":"LP Santos Pimenta","year":"2014","unstructured":"Santos Pimenta, L. P., Schilthuizen, M., Verpoorte, R. & Choi, Y. H. Quantitative analysis of amygdalin and prunasin in prunus serotina Ehrh using 1H-NMR spectroscopy. Phytochem. Anal. 25, 122\u2013126. https:\/\/doi.org\/10.1002\/pca.2476 (2014).","journal-title":"Phytochem. Anal."},{"key":"93620_CR23","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.13005\/bpj\/2693","volume":"16","author":"PC Semwal","year":"2023","unstructured":"Semwal, P. C., Semwal, A., Bhatt, S., Parashar, T. & Jakhmola, V. Apricot-a new source of chemically active constituents: a medicinal overview. Biomed. pharmacol. J. 16, 1133\u20131142 (2023).","journal-title":"Biomed. pharmacol. J."},{"key":"93620_CR24","first-page":"125","volume":"14","author":"V Jaswal","year":"2018","unstructured":"Jaswal, V., Palanivelu, J. & Ramalingam, C. Effects of the gut microbiota on amygdalin and its use as an anti-cancer therapy: Substantial review on the key components involved in altering dose efficacy and toxicity. Biochem. Biophys. Rep. 14, 125\u2013132 (2018).","journal-title":"Biochem. Biophys. Rep."},{"key":"93620_CR25","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1111\/j.1556-4029.2012.02138.x","volume":"57","author":"VM Toomey","year":"2012","unstructured":"Toomey, V. M., Nickum, E. A. & Flurer, C. L. Cyanide and amygdalin as indicators of the presence of bitter almonds in imported raw almonds. J. Forensic Sci. 57, 1313\u20131317 (2012).","journal-title":"J. Forensic Sci."},{"key":"93620_CR26","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/j.ejmhg.2014.05.001","volume":"15","author":"J Minari","year":"2014","unstructured":"Minari, J. Chemopreventive effect of Annona muricata on DMBA-induced cell proliferation in the breast tissues of female albino mice. Egypt. J. Med. Hum. Genet. 15, 327\u2013334 (2014).","journal-title":"Egypt. J. Med. Hum. Genet."},{"key":"93620_CR27","first-page":"235","volume":"52","author":"KC Fendl","year":"1992","unstructured":"Fendl, K. C. & Zimniski, S. J. Role of Tamoxifen in the Induction of Hormone-independent Rat Mammary Tumors1. Cancer Res. 52, 235\u2013237 (1992).","journal-title":"Cancer Res."},{"key":"93620_CR28","doi-asserted-by":"publisher","first-page":"1566","DOI":"10.1345\/aph.1E634","volume":"39","author":"J Bromley","year":"2005","unstructured":"Bromley, J., Hughes, B. G. M., Leong, D. C. S. & Buckley, N. A. Life-threatening interaction between complementary medicines: Cyanide toxicity following ingestion of amygdalin and vitamin C. Ann. Pharmacother. 39, 1566\u20131569. https:\/\/doi.org\/10.1345\/aph.1E634 (2005).","journal-title":"Ann. Pharmacother."},{"key":"93620_CR29","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1111\/fcp.12397","volume":"33","author":"B Karimi","year":"2019","unstructured":"Karimi, B., Ashrafi, M., Shomali, T. & Yektaseresht, A. Therapeutic effect of simvastatin on DMBA-induced breast cancer in mice. Fundam. Clin. Pharmacol. 33, 84\u201393. https:\/\/doi.org\/10.1111\/fcp.12397 (2019).","journal-title":"Fundam. Clin. Pharmacol."},{"key":"93620_CR30","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0203793","volume":"13","author":"N Marquardt","year":"2018","unstructured":"Marquardt, N. et al. Euthanasia of laboratory mice: Are isoflurane and sevoflurane real alternatives to carbon dioxide?. PloS one 13, e0203793 (2018).","journal-title":"PloS one"},{"key":"93620_CR31","unstructured":"Young, D. Effects of drugs on clinical laboratory tests. Third. Vol. 3 (1990)."},{"key":"93620_CR32","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1159\/000459586","volume":"12","author":"A Belfield","year":"1971","unstructured":"Belfield, A. & Goldenberg, D. M. Enzyme. 12, 561 (1971).","journal-title":"M. Enzyme."},{"key":"93620_CR33","unstructured":"Tietz, N. W. in Clinical guide to laboratory tests 1096\u20131096 (1995)."},{"key":"93620_CR34","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1093\/clinchem\/26.5.555","volume":"26","author":"LD Bowers","year":"1980","unstructured":"Bowers, L. D. & Wong, E. T. Kinetic serum creatinine assays. II. A critical evaluation and review. Clin. Chem. 26, 555\u2013561. https:\/\/doi.org\/10.1093\/clinchem\/26.5.555 (1980).","journal-title":"Clin. Chem."},{"key":"93620_CR35","doi-asserted-by":"crossref","unstructured":"Sugarbaker, P. H. in Advances in Immunity and Cancer Therapy: Volume 1 (ed P. K. Ray) 167\u2013193 (Springer New York, 1985).","DOI":"10.1007\/978-1-4612-5068-5_5"},{"key":"93620_CR36","doi-asserted-by":"publisher","first-page":"2831","DOI":"10.1002\/1097-0142(19921215)70:12<2831::AID-CNCR2820701218>3.0.CO;2-8","volume":"70","author":"JG Geraghty","year":"1992","unstructured":"Geraghty, J. G., Coveney, E. C., Sherry, F., O\u2019Higgins, N. J. & Dufy, M. J. CA 15\u20133 in patients with locoregional and metastatic breast carcinoma. Cancer 70, 2831\u20132834. https:\/\/doi.org\/10.1002\/1097-0142(19921215)70:12%3c2831::AID-CNCR2820701218%3e3.0.CO;2-8 (1992).","journal-title":"Cancer"},{"key":"93620_CR37","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1097\/00000441-198607000-00005","volume":"292","author":"Y Haga","year":"1986","unstructured":"Haga, Y., Sakamoto, K., Egami, H., Yoshimura, R. & Akagi, M. Evaluation of Serum CA125 Values in Healthy Individuals and Pregnant Women. Am. J. Med. Sci. 292, 25\u201329. https:\/\/doi.org\/10.1097\/00000441-198607000-00005 (1986).","journal-title":"Am. J. Med. Sci."},{"key":"93620_CR38","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1210\/jcem-53-2-443","volume":"53","author":"B Martin","year":"1981","unstructured":"Martin, B., Rotten, D., Jolivet, A. & Gautray, J. P. Binding of Steroids by Proteins in Follicular Fluid of the Human Ovary. J. Clin. Endocrinol. Metab. 53, 443\u2013447. https:\/\/doi.org\/10.1210\/jcem-53-2-443 (1981).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"93620_CR39","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/0022-1759(81)90219-2","volume":"42","author":"M Uotila","year":"1981","unstructured":"Uotila, M., Ruoslahti, E. & Engvall, E. Two-site sandwich enzyme immunoassay with monoclonal antibodies to human alpha-fetoprotein. J. Immunol. Methods 42, 11\u201315. https:\/\/doi.org\/10.1016\/0022-1759(81)90219-2 (1981).","journal-title":"J. Immunol. Methods"},{"key":"93620_CR40","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1016\/S0006-291X(72)80218-3","volume":"46","author":"M Nishikimi","year":"1972","unstructured":"Nishikimi, M., Appaji Rao, N. & Yagi, K. The occurrence of superoxide anion in the reaction of reduced phenazine methosulfate and molecular oxygen. Biochem. Biophys. Res. Commun. 46, 849\u2013854. https:\/\/doi.org\/10.1016\/S0006-291X(72)80218-3 (1972).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"93620_CR41","first-page":"158","volume":"70","author":"DE Paglia","year":"1967","unstructured":"Paglia, D. E. & Valentine, W. N. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J. Lab. Clin. Med. 70, 158\u2013169 (1967).","journal-title":"J. Lab. Clin. Med."},{"key":"93620_CR42","doi-asserted-by":"publisher","first-page":"3655","DOI":"10.2147\/IJN.S111279","volume":"11","author":"X-F Zhang","year":"2016","unstructured":"Zhang, X.-F. & Gurunathan, S. Combination of salinomycin and silver nanoparticles enhances apoptosis and autophagy in human ovarian cancer cells: an effective anticancer therapy. Int. J. Nanomedicine. 11, 3655\u20133675. https:\/\/doi.org\/10.2147\/IJN.S111279 (2016).","journal-title":"Int. J. Nanomedicine."},{"key":"93620_CR43","doi-asserted-by":"publisher","first-page":"6537","DOI":"10.2147\/IJN.S125281","volume":"12","author":"Y-G Yuan","year":"2017","unstructured":"Yuan, Y.-G. & Gurunathan, S. Combination of graphene oxide\u2013silver nanoparticle nanocomposites and cisplatin enhances apoptosis and autophagy in human cervical cancer cells. Int. J. Nanomedicine. 12, 6537\u20136558. https:\/\/doi.org\/10.2147\/IJN.S125281 (2017).","journal-title":"Int. J. Nanomedicine."},{"key":"93620_CR44","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1080\/00071668.2014.925090","volume":"55","author":"E Gasparino","year":"2014","unstructured":"Gasparino, E. et al. The effect of heat stress on GHR, IGF-I, ANT, UCP and COXIII mRNA expression in the liver and muscle of high and low feed efficiency female quail. Br. Poult. Sci. 55, 466\u2013473. https:\/\/doi.org\/10.1080\/00071668.2014.925090 (2014).","journal-title":"Br. Poult. Sci."},{"key":"93620_CR45","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1089\/scd.1.1993.2.387","volume":"2","author":"DJ Recktenwald","year":"1993","unstructured":"Recktenwald, D. J. Introduction to Flow Cytometry: Principles, Fluorochromes, Instrument Set-up. Calibration. J. Chemother. 2, 387\u2013394. https:\/\/doi.org\/10.1089\/scd.1.1993.2.387 (1993).","journal-title":"Calibration. J. Chemother."},{"key":"93620_CR46","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1083\/jcb.60.2.523","volume":"60","author":"PN Dean","year":"1974","unstructured":"Dean, P. N. & Jett, J. H. Mathematical analysis of DNA distributions derived from flow microfluorometry. J. Cell Biol. 60, 523 (1974).","journal-title":"J. Cell Biol."},{"key":"93620_CR47","unstructured":"Bancroft, J. D. & Gamble, M. Theory and Practice of Histological Techniques. (Churchill Livingstone, 2008)."},{"key":"93620_CR48","unstructured":"Steel, R. G. Pinciples and procedures of statistics a biometrical approach. 3rd ed edn, (1997)."},{"key":"93620_CR49","doi-asserted-by":"publisher","first-page":"1584","DOI":"10.1016\/j.fct.2009.04.005","volume":"47","author":"AS El-Sharaky","year":"2009","unstructured":"El-Sharaky, A. S., Newairy, A. A., Kamel, M. A. & Eweda, S. M. Protective effect of ginger extract against bromobenzene-induced hepatotoxicity in male rats. Food and Chem Toxicol 47, 1584\u20131590. https:\/\/doi.org\/10.1016\/j.fct.2009.04.005 (2009).","journal-title":"Food and Chem Toxicol"},{"key":"93620_CR50","doi-asserted-by":"publisher","first-page":"486","DOI":"10.2174\/1871520620666200120095525","volume":"20","author":"MA El-Desouky","year":"2020","unstructured":"El-Desouky, M. A., Fahmi, A. A., Abdelkader, I. Y. & Nasraldin, K. M. Anticancer effect of amygdalin (vitamin B-17) on hepatocellular carcinoma cell line (HepG2) in the presence and absence of zinc. Anticancer Agents Med. Chem. 20, 486\u2013494 (2020).","journal-title":"Anticancer Agents Med. Chem."},{"key":"93620_CR51","doi-asserted-by":"crossref","unstructured":"Ali, S. A., Ibrahim, N. A., Mohammed, M. M., El-Hawary, S. & Refaat, E. A. The potential chemo preventive effect of ursolic acid isolated from Paulownia tomentosa, against N-diethylnitrosamine: initiated and promoted hepatocarcinogenesis. Heliyon 5 (2019).","DOI":"10.1016\/j.heliyon.2019.e01769"},{"key":"93620_CR52","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.3892\/mmr.2013.1391","volume":"7","author":"J Guo","year":"2013","unstructured":"Guo, J., Wu, W., Sheng, M., Yang, S. & Tan, J. Amygdalin inhibits renal fibrosis in chronic kidney disease. Mol. Med. Rep. 7, 1453\u20131457. https:\/\/doi.org\/10.3892\/mmr.2013.1391 (2013).","journal-title":"Mol. Med. Rep."},{"key":"93620_CR53","doi-asserted-by":"publisher","first-page":"483","DOI":"10.3390\/nu11020483","volume":"11","author":"Z Dong","year":"2019","unstructured":"Dong, Z., Sun, Y., Wei, G., Li, S. & Zhao, Z. Ergosterol ameliorates diabetic nephropathy by attenuating mesangial cell proliferation and extracellular matrix deposition via the TGF-\u03b21\/Smad2 signaling pathway. Nutrients 11, 483 (2019).","journal-title":"Nutrients"},{"key":"93620_CR54","doi-asserted-by":"publisher","first-page":"526","DOI":"10.3892\/ijmm.2015.2439","volume":"37","author":"E Juengel","year":"2016","unstructured":"Juengel, E. et al. Amygdalin inhibits the growth of renal cell carcinoma cells in vitro. Int. J. Mol. Med. 37, 526\u2013532. https:\/\/doi.org\/10.3892\/ijmm.2015.2439 (2016).","journal-title":"Int. J. Mol. Med."},{"key":"93620_CR55","doi-asserted-by":"crossref","unstructured":"Koles\u00e1r, E., Halen\u00e1r, M., Koles\u00e1rov\u00e1, A. & Mass\u00e1nyi, P. Natural plant toxicant-cyanogenic glycoside amygdalin: characteristic, metabolism and the effect on animal reproduction. J. Microbiol. Biotechnol. Food Sci. 4 (2015).","DOI":"10.15414\/jmbfs.2015.4.special2.49-50"},{"key":"93620_CR56","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1080\/10934529.2012.672144","volume":"47","author":"A Kolesarova","year":"2012","unstructured":"Kolesarova, A. et al. Resveratrol inhibits reproductive toxicity induced by deoxynivalenol. J. Environ. Sci. Health A. 47, 1329\u20131334. https:\/\/doi.org\/10.1080\/10934529.2012.672144 (2012).","journal-title":"J. Environ. Sci. Health A."},{"key":"93620_CR57","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.bbrep.2018.04.008","volume":"14","author":"V Jaswal","year":"2018","unstructured":"Jaswal, V., Palanivelu, J. & C, R.,. Effects of the Gut microbiota on Amygdalin and its use as an anti-cancer therapy: Substantial review on the key components involved in altering dose efficacy and toxicity. Biochem. Biophys. Rep. 14, 125\u2013132. https:\/\/doi.org\/10.1016\/j.bbrep.2018.04.008 (2018).","journal-title":"Biochem. Biophys. Rep."},{"key":"93620_CR58","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1002\/(SICI)1097-0215(19981209)78:6<712::AID-IJC8>3.0.CO;2-D","volume":"78","author":"KN Syrigos","year":"1998","unstructured":"Syrigos, K. N., Rowlinson-Busza, G. & Epenetos, A. A. In vitro cytotoxicity following specific activation of amygdalin by \u03b2-glucosidase conjugated to a bladder cancer-associated monoclonal antibody. Int. J. Cancer. 78, 712\u2013719. https:\/\/doi.org\/10.1002\/(SICI)1097-0215(19981209)78:6%3c712::AID-IJC8%3e3.0.CO;2-D (1998).","journal-title":"Int. J. Cancer."},{"key":"93620_CR59","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1007\/s11655-015-2154-x","volume":"24","author":"Y-L Li","year":"2018","unstructured":"Li, Y.-L., Li, Q.-X., Liu, R.-J. & Shen, X.-Q. Chinese Medicine Amygdalin and \u03b2-Glucosidase Combined with Antibody Enzymatic Prodrug System As A Feasible Antitumor Therapy. Chin. J. Integr. Med. 24, 237\u2013240. https:\/\/doi.org\/10.1007\/s11655-015-2154-x (2018).","journal-title":"Chin. J. Integr. Med."},{"key":"93620_CR60","first-page":"555","volume":"2","author":"A Alam","year":"2018","unstructured":"Alam, A. et al. Chemotherapy treatment and strategy schemes: A review. Open Acc. J. of Toxicol 2, 555\u2013600 (2018).","journal-title":"Open Acc. J. of Toxicol"},{"key":"93620_CR61","doi-asserted-by":"crossref","unstructured":"Gill, S. S., Gill, R. K. & Sobti, R. in Handbook of Oncobiology: From Basic to Clinical Sciences 259\u2013296 (Springer, 2024).","DOI":"10.1007\/978-981-99-6263-1_7"},{"key":"93620_CR62","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.fct.2014.04.036","volume":"70","author":"AB Karabulut","year":"2014","unstructured":"Karabulut, A. B. et al. Apricot attenuates oxidative stress and modulates of Bax, Bcl-2, caspases, NF\u03ba-B, AP-1, CREB expression of rats bearing DMBA-induced liver damage and treated with a combination of radiotherapy. Food and Chem. Toxicol. 70, 128\u2013133. https:\/\/doi.org\/10.1016\/j.fct.2014.04.036 (2014).","journal-title":"Food and Chem. Toxicol."},{"key":"93620_CR63","doi-asserted-by":"publisher","first-page":"621","DOI":"10.2174\/1871520620666200608124003","volume":"21","author":"S Hosny","year":"2021","unstructured":"Hosny, S., Sahyon, H., Youssef, M. & Negm, A. Prunus Armeniaca L. seed extract and its amygdalin containing fraction induced mitochondrial-mediated apoptosis and autophagy in liver carcinogenesis. Anticancer Agents Med. Chem. 21, 621\u2013629 (2021).","journal-title":"Anticancer Agents Med. Chem."},{"key":"93620_CR64","first-page":"4969","volume":"52","author":"JS Lim","year":"1992","unstructured":"Lim, J. S., Frenkel, K. & Troll, W. Tamoxifen suppresses tumor promoter-induced hydrogen peroxide formation by human neutrophils1. Cancer Res. 52, 4969\u20134972 (1992).","journal-title":"Cancer Res."},{"key":"93620_CR65","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1002\/cbdv.200900022","volume":"6","author":"B Testa","year":"2009","unstructured":"Testa, B. & Kraemer, S. D. The biochemistry of drug metabolism\u2013an introduction: part 5. Metab. Bioact. Chem. Biodiv. 6, 591\u2013684 (2009).","journal-title":"Metab. Bioact. Chem. Biodiv."},{"key":"93620_CR66","doi-asserted-by":"publisher","first-page":"1891","DOI":"10.1002\/jcb.30331","volume":"123","author":"MR Patil","year":"2022","unstructured":"Patil, M. R. & Bihari, A. A comprehensive study of p53 protein. J. Cell. Biochem. 123, 1891\u20131937 (2022).","journal-title":"J. Cell. Biochem."},{"key":"93620_CR67","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.985363","volume":"12","author":"S Qian","year":"2022","unstructured":"Qian, S. et al. The role of BCL-2 family proteins in regulating apoptosis and cancer therapy. Front. Oncol. 12, 985363 (2022).","journal-title":"Front. Oncol."},{"key":"93620_CR68","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.cbpa.2017.06.014","volume":"39","author":"TP Garner","year":"2017","unstructured":"Garner, T. P., Lopez, A., Reyna, D. E., Spitz, A. Z. & Gavathiotis, E. Progress in targeting the BCL-2 family of proteins. Curr. Opin. Chem. Biol. 39, 133\u2013142 (2017).","journal-title":"Curr. Opin. Chem. Biol."},{"key":"93620_CR69","doi-asserted-by":"publisher","first-page":"11333","DOI":"10.1073\/pnas.91.24.11333","volume":"91","author":"M Truss","year":"1994","unstructured":"Truss, M., Bartsch, J. & Beato, M. Antiprogestins prevent progesterone receptor binding to hormone responsive elements in vivo. Proc. Natl. Acad. Sci. 91, 11333\u201311337 (1994).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"93620_CR70","doi-asserted-by":"publisher","first-page":"1424","DOI":"10.1182\/blood.V63.6.1424.1424","volume":"63","author":"K Anderson","year":"1984","unstructured":"Anderson, K. et al. Expression of human B cell-associated antigens on leukemias and lymphomas: a model of human B cell differentiation. Blood 63, 1424\u20131433. https:\/\/doi.org\/10.1182\/blood.V63.6.1424.1424 (1984).","journal-title":"Blood"},{"key":"93620_CR71","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1038\/nrc3023","volume":"11","author":"M Z\u00f6ller","year":"2011","unstructured":"Z\u00f6ller, M. CD44: can a cancer-initiating cell profit from an abundantly expressed molecule?. Nat. Rev. Cancer. 11, 254\u2013267 (2011).","journal-title":"Nat. Rev. Cancer."},{"key":"93620_CR72","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1186\/1471-2407-11-418","volume":"11","author":"E Olsson","year":"2011","unstructured":"Olsson, E. et al. CD44 isoforms are heterogeneously expressed in breast cancer and correlate with tumor subtypes and cancer stem cell markers. BMC Cancer 11, 418. https:\/\/doi.org\/10.1186\/1471-2407-11-418 (2011).","journal-title":"BMC Cancer"},{"key":"93620_CR73","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1172\/JCI39397","volume":"120","author":"C Ginestier","year":"2010","unstructured":"Ginestier, C. et al. CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts. J. Clin. Investig. 120, 485\u2013497 (2010).","journal-title":"J. Clin. Investig."},{"key":"93620_CR74","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0106966","volume":"9","author":"SM Smith","year":"2014","unstructured":"Smith, S. M., Lyu, Y. L. & Cai, L. NF-\u03baB affects proliferation and invasiveness of breast cancer cells by regulating CD44 expression. PloS one 9, e106966 (2014).","journal-title":"PloS one"},{"key":"93620_CR75","doi-asserted-by":"publisher","first-page":"9236","DOI":"10.3390\/ijms16059236","volume":"16","author":"M Fantini","year":"2015","unstructured":"Fantini, M. et al. In vitro and in vivo antitumoral effects of combinations of polyphenols, or polyphenols and anticancer drugs: Perspectives on cancer treatment. Int. J. Mol. Sci. 16, 9236\u20139282 (2015).","journal-title":"Int. J. Mol. Sci."},{"key":"93620_CR76","doi-asserted-by":"publisher","first-page":"4199","DOI":"10.2741\/3523","volume":"14","author":"A Maya-Mendoza","year":"2009","unstructured":"Maya-Mendoza, A., Tang, C. W., Pombo, A. & Jackson, D. A. Mechanisms regulating S phase progression in mammalian cells. Front. Biosci. 14, 4199\u20134213 (2009).","journal-title":"Front. Biosci."},{"key":"93620_CR77","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.ecoenv.2014.11.011","volume":"113","author":"S Anbumani","year":"2015","unstructured":"Anbumani, S. & Mohankumar, M. N. Gamma radiation induced cell cycle perturbations and DNA damage in Catla Catla as measured by flow cytometry. Ecotoxicol. Environ. Saf. 113, 18\u201322 (2015).","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"93620_CR78","first-page":"84","volume":"5","author":"A Hosseini","year":"2015","unstructured":"Hosseini, A. & Ghorbani, A. Cancer therapy with phytochemicals: evidence from clinical studies. Avicenna. J. Phytomed. 5, 84\u201397 (2015).","journal-title":"Avicenna. J. Phytomed."},{"key":"93620_CR79","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1016\/S1534-5807(03)00090-X","volume":"4","author":"S Arur","year":"2003","unstructured":"Arur, S. et al. Annexin I is an endogenous ligand that mediates apoptotic cell engulfment. Dev. Cell 4, 587\u2013598 (2003).","journal-title":"Dev. Cell"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-93620-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-93620-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-93620-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T09:04:11Z","timestamp":1742202251000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-93620-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,17]]},"references-count":79,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["93620"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-93620-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,17]]},"assertion":[{"value":"22 September 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 March 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 March 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The study was approved by the Committee of Research Ethics, School of Veterinary Medicine at Benha University (BUFVTM 18\u201301-23).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Institutional review board statement"}}],"article-number":"9131"}}