{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:54:29Z","timestamp":1791237269771,"version":"4.1.0"},"reference-count":39,"publisher":"Radiation Research Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2026,4,10]]},"abstract":"<jats:p>Apigenin inhibits proliferation and induces apoptosis in triple-negative breast cancer (TNBC) cells, processes linked to DNA damage. However, the combined effect of apigenin and radiation on TNBC cells remains unclear. This study aimed to determine whether apigenin enhances the radiosensitivity of TNBC cells by activating the cGAS-STING pathway. Human TNBC cell lines MDA-MB-231 and MDA-MB-468 were X-ray irradiated, and the optimal apigenin concentration was determined by CCK-8 assay. Protein expression was analyzed by western blot, and cGAS or STING was knocked down using siRNA. DNA damage was assessed by immunofluorescence quantification of \u03b3H2AX and cytoplasmic dsDNA foci, while apoptosis was measured by flow cytometry. At 15 \u00b5M, apigenin showed minimal toxicity and enhanced radiosensitivity in both cell lines. Ionizing radiation increased cytosolic dsDNA levels and micronuclei formation, which was associated with upregulated cGAS-STING-TBK1-IRF3 pathway activity. Apigenin further enhanced this pathway by increasing radiation-induced cytosolic dsDNA and micronuclei, thereby promoting TNBC cell apoptosis. Moreover, knockdown of cGAS or STING significantly attenuated the apoptotic response induced by the combination of apigenin and radiation. These findings suggest that apigenin enhances the radiosensitivity of TNBC cells by activating the tumor cell-intrinsic cGAS-STING pathway.<\/jats:p>","DOI":"10.1667\/rade-25-00117.1","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T09:41:26Z","timestamp":1778146886000},"page":"502-512","source":"Crossref","is-referenced-by-count":0,"title":["Apigenin Enhances the Radiosensitivity of TNBC Cells by Improving cGAS-STING Pathway Activity"],"prefix":"10.1667","volume":"205","author":[{"given":"Xiongxiong","family":"Liu","sequence":"first","affiliation":[{"name":"Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youming","family":"Zhu","sequence":"additional","affiliation":[{"name":"The First People's Hospital of Taian, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Zheng","sequence":"additional","affiliation":[{"name":"Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"AC Garrido-Castro, NU Lin, K Polyak,  \"Cancer Discov.\"  9, \"Insights into Molecular Classifications of Triple-Negative Breast Cancer: Improving Patient Selection for Treatment.\" 176 (2019)","DOI":"10.1158\/2159-8290.CD-18-1177"},{"key":"2","doi-asserted-by":"crossref","unstructured":"G Bianchini, C De Angelis, L Licata, et al.  \"Nat Rev Clin Oncol.\"  19, \"Treatment landscape of triple-negative breast cancer - expanded options, evolving needs.\" 91 (2022)","DOI":"10.1038\/s41571-021-00565-2"},{"key":"3","doi-asserted-by":"crossref","unstructured":"P Schmid, J Cortes, L Pusztai,  \"N Engl J Med.\"  382, \"Pembrolizumab for Early Triple-Negative Breast Cancer.\" 810 (2020)","DOI":"10.1056\/NEJMoa1910549"},{"key":"5","doi-asserted-by":"crossref","unstructured":"H Kumar, NV Gupta, R Jain, et al.  \"J Adv Res.\"  54, \"A review of biological targets and therapeutic approaches in the management of triple-negative breast cancer.\" 271 (2023)","DOI":"10.1016\/j.jare.2023.02.005"},{"key":"6","doi-asserted-by":"crossref","unstructured":"TE Keenan  and SM Tolaney  \"J Natl Compr Canc Netw.\"  18, \"Role of Immunotherapy in Triple-Negative Breast Cancer.\" 479 (2020)","DOI":"10.6004\/jnccn.2020.7554"},{"key":"7","doi-asserted-by":"crossref","unstructured":"Y Gan, X Li, S Han, et al.  \"Front Immunol.\"  12, \"The cGAS\/STING Pathway: A Novel Target for Cancer Therapy.\" 795401 (2022)","DOI":"10.3389\/fimmu.2021.795401"},{"key":"8","doi-asserted-by":"crossref","unstructured":"F Shi, J Su, J Wang, et al.  \"Mol Cell Biochem.\"  476, \"Activation of STING inhibits cervical cancer tumor growth through enhancing the anti-tumor immune response.\" 1015 (2021)","DOI":"10.1007\/s11010-020-03967-5"},{"key":"9","doi-asserted-by":"crossref","unstructured":"A Amouzegar, M Chelvanambi, JN Filderman, et al.  \"Cancers.\"  13, \"STING Agonists as Cancer Therapeutics.\" 2695 (2021)","DOI":"10.3390\/cancers13112695"},{"key":"11","doi-asserted-by":"crossref","unstructured":"AH Rahmani, MA Alsahli, A Almatroudi, et al.  \"Molecules.\"  27, \"The Potential Role of Apigenin in Cancer Prevention and Treatment.\" 6051 (2022)","DOI":"10.3390\/molecules27186051"},{"key":"12","doi-asserted-by":"crossref","unstructured":"YW Li, J Xu, GY Zhu, et al.  \"Cell Death Discov.\"  4, \"Apigenin suppresses the stem cell-like properties of triple-negative breast cancer cells by inhibiting YAP\/TAZ activity.\" 105 (2018)","DOI":"10.1038\/s41420-018-0124-8"},{"key":"13","doi-asserted-by":"crossref","unstructured":"X Liu, Q Wang, B Liu, et al.  \"Radiother Oncol.\"  155, \"Genistein inhibits radiation-induced invasion and migration of glioblastoma cells by blocking the DNA-PKcs\/Akt2\/Rac1 signaling pathway.\" 93 (2021)","DOI":"10.1016\/j.radonc.2020.10.026"},{"key":"14","doi-asserted-by":"crossref","unstructured":"J Marill, N Mohamed Anesary, S Paris,  \"Radiother Oncol.\"  141, \"DNA damage enhancement by radiotherapy-activated hafnium oxide nanoparticles improves cGAS-STING pathway activation in human colorectal cancer cells.\" 262 (2019)","DOI":"10.1016\/j.radonc.2019.07.029"},{"key":"15","doi-asserted-by":"crossref","unstructured":"S Shukla, P Fu, S Gupta,  \"Apoptosis.\"  19, \"Apigenin induces apoptosis by targeting inhibitor of apoptosis proteins and Ku70-Bax interaction in prostate cancer.\" 883 (2014)","DOI":"10.1007\/s10495-014-0971-6"},{"key":"16","doi-asserted-by":"crossref","unstructured":"N Begum, PN Rajendra, G Kanimozhi, et al.  \"Nat Prod Res.\"  36, \"Apigenin prevents gamma radiation-induced gastrointestinal damages by modulating inflammatory and apoptotic signalling mediators.\" 1631 (2022)","DOI":"10.1080\/14786419.2021.1893316"},{"key":"17","doi-asserted-by":"crossref","unstructured":"A Ra\u0161kovi'c, S Gigov, I \u010capo, et al.  \"Eur J Drug Metab Pharmacokinet.\"  42, \"Antioxidative and Protective Actions of Apigenin in a Paracetamol-Induced Hepatotoxicity Rat Model.\" 849 (2017)","DOI":"10.1007\/s13318-017-0407-0"},{"key":"18","doi-asserted-by":"crossref","unstructured":"N Begum  and NR Prasad  \"Biomed Prev Nutr.\"  2, \"Apigenin, a Dietary Antioxidant, Modulates Gamma Radiation-Induced Oxidative Damages in Human Peripheral Blood Lymphocytes.\" 16 (2012)","DOI":"10.1016\/j.bionut.2011.11.003"},{"key":"19","doi-asserted-by":"crossref","unstructured":"WJ Hu, J Liu, LK Zhong, et al.  \"Biomed Pharmacother.\"  102, \"Apigenin enhances the antitumor effects of cetuximab in nasopharyngeal carcinoma by inhibiting EGFR signaling.\" 681 (2018)","DOI":"10.1016\/j.biopha.2018.03.111"},{"key":"20","doi-asserted-by":"crossref","unstructured":"M Granato, MS Gilardini Montani, R Santarelli, et al.  \"J Exp Clin Cancer Res.\"  36, \"Apigenin, by activating p53 and inhibiting STAT3, modulates the balance between pro-apoptotic and pro-survival pathways to induce PEL cell death.\" 167 (2017)","DOI":"10.1186\/s13046-017-0632-z"},{"key":"21","doi-asserted-by":"crossref","unstructured":"S Shukla  and S Gupta  \"Mol Cancer Ther.\"  5, \"Molecular targets for apigenin-induced cell cycle arrest and apoptosis in prostate cancer cell xenograft.\" 843 (2006)","DOI":"10.1158\/1535-7163.MCT-05-0370"},{"key":"23","doi-asserted-by":"crossref","unstructured":"Y Zhou, YJ Yu, H Lv, et al.  \"Food Chem Toxicol.\"  168, \"Apigenin in cancer therapy: From mechanism of action to nano-therapeutic agent.\" 113385 (2022)","DOI":"10.1016\/j.fct.2022.113385"},{"key":"26","doi-asserted-by":"crossref","unstructured":"Y Sato  and MT Hayashi  \"Life Sci Alliance.\"  7, \"Micronucleus is not a potent inducer of the cGAS\/STING pathway.\" e202302424 (2024)","DOI":"10.26508\/lsa.202302424"},{"key":"27","doi-asserted-by":"crossref","unstructured":"KN Rithidech, M Tungjai, EB Whorton,  \"Mutat Res.\"  585, \"Protective effect of apigenin on radiation-induced chromosomal damage in human lymphocytes.\" 96 (2005)","DOI":"10.1016\/j.mrgentox.2005.04.003"},{"key":"28","doi-asserted-by":"crossref","unstructured":"NK. Sharma,  \"J Radiat Res.\"  54, \"Modulation of radiation-induced and mitomycin C-induced chromosome damage by apigenin in human lymphocytes in vitro.\" 789 (2013)","DOI":"10.1093\/jrr\/rrs117"},{"key":"29","doi-asserted-by":"crossref","unstructured":"M. Riera Romo,  \"Immunology.\"  163, \"Cell death as part of innate immunity: Cause or consequence?\" 399 (2021)","DOI":"10.1111\/imm.13325"},{"key":"30","doi-asserted-by":"crossref","unstructured":"R Huang, Q Shi, S Zhang, et al.  \"J Inflamm Res.\"  15, \"Inhibition of the cGAS-STING Pathway Attenuates Lung Ischemia\/Reperfusion Injury via Regulating Endoplasmic Reticulum Stress in Alveolar Epithelial Type II Cells of Rats.\" 5103 (2022)","DOI":"10.2147\/JIR.S365970"},{"key":"31","doi-asserted-by":"crossref","unstructured":"W Wang, D Hu, C Wu, et al.  \"PLoS Pathog.\"  16, \"STING promotes NLRP3 localization in ER and facilitates NLRP3 deubiquitination to activate the inflammasome upon HSV-1 infection.\" e1008335 (2020)","DOI":"10.1371\/journal.ppat.1008335"},{"key":"32","doi-asserted-by":"crossref","unstructured":"S Chattopadhyay, M Yamashita, Y Zhang, et al.  \"J Virol.\"  85, \"The IRF-3\/ Bax-mediated apoptotic pathway, activated by viral cytoplasmic RNA and DNA, inhibits virus replication.\" 3708 (2011)","DOI":"10.1128\/JVI.02133-10"},{"key":"33","doi-asserted-by":"crossref","unstructured":"D Goubau, R Romieu-Mourez, M Solis, et al.  \"Eur J Immunol.\"  39, \"Transcriptional re-programming of primary macrophages reveals distinct apoptotic and anti-tumoral functions of IRF-3 and IRF-7.\" 527 (2009)","DOI":"10.1002\/eji.200838832"},{"key":"34","doi-asserted-by":"crossref","unstructured":"J Petrasek, A Iracheta-Vellve, T Csak, et al.  \"Proc Natl Acad Sci U S A.\"  110, \"STING-IRF3 pathway links endoplasmic reticulum stress with hepatocyte apoptosis in early alcoholic liver disease.\" 16544 (2013)","DOI":"10.1073\/pnas.1308331110"},{"key":"35","doi-asserted-by":"crossref","unstructured":"SS Park, YJ Kim, EJ Ju, et al.  \"Radiother Oncol.\"  112, \"Ibulocydine sensitizes human cancers to radiotherapy by induction of mitochondria-mediated apoptosis.\" 295 (2014)","DOI":"10.1016\/j.radonc.2014.07.005"},{"key":"36","doi-asserted-by":"crossref","unstructured":"M Asadi, S Taghizadeh, E Kaviani, et al.  \"Biotechnol Appl Biochem.\"  69, \"Caspase-3: Structure, function, and biotechnological aspects.\" 1633 (2022)","DOI":"10.1002\/bab.2233"},{"key":"37","doi-asserted-by":"crossref","unstructured":"B Zhang, J Wang, G Zhao, et al.  \"Cell Stress Chaperones.\"  25, \"Apigenin protects human melanocytes against oxidative damage by activation of the Nrf2 pathway.\" 277 (2020)","DOI":"10.1007\/s12192-020-01071-7"},{"key":"38","doi-asserted-by":"crossref","unstructured":"H Zhang, Y Cao, L Jiao, et al.  \"Dose Response.\"  23, \"Apigenin Inhibits Cell Ferroptosis by Activating the PI3K\/Akt Pathway and Alleviates Renal Injury Caused by Hypertension.\" 15593258251335814 (2025)","DOI":"10.1177\/15593258251335814"},{"key":"39","doi-asserted-by":"crossref","unstructured":"L Zhang, H Li, S Xu, et al.  \"Turk J Biol.\"  49, \"Apigenin attenuates ischemia-reperfusion-induced pulmonary ferroptosis and fibrosis by activating the Nrf2\/HO-1\/GPX4 axis in mice.\" 138 (2024)","DOI":"10.55730\/1300-0152.2732"},{"key":"24","doi-asserted-by":"crossref","unstructured":"Z Dou, K Ghosh, MG Vizioli, et al.  \"Nature.\"  550, \"Cytoplasmic chromatin triggers inflammation in senescence and cancer.\" 402 (2017)","DOI":"10.1038\/nature24050"},{"key":"25","doi-asserted-by":"crossref","unstructured":"C Vanpouille-Box, A Alard, MJ Aryankalayil, et al.  \"Nat Commun.\"  8, \"DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity.\" 15618 (2017)","DOI":"10.1038\/ncomms15618"},{"key":"10","doi-asserted-by":"crossref","unstructured":"B Salehi, A Venditti, M Sharifi-Rad, et al.  \"Int J Mol Sci.\"  20, \"The therapeutic potential of apigenin.\" 1305 (2019)","DOI":"10.3390\/ijms20061305"},{"key":"22","doi-asserted-by":"crossref","unstructured":"J Yang, C Pi, G Wang,  \"Biomed Pharmacother.\"  103, \"Inhibition of PI3K\/Akt\/mTOR pathway by apigenin induces apoptosis and autophagy in hepatocellular carcinoma cells.\" 699 (2018)","DOI":"10.1016\/j.biopha.2018.04.072"},{"key":"4","doi-asserted-by":"crossref","unstructured":"MY He, C Rancoule, A Rehailia-Blanchard, et al.  \"Crit Rev Oncol Hematol.\"  131, \"Radiotherapy in triple-negative breast cancer: Current situation and upcoming strategies.\" 96 (2018)","DOI":"10.1016\/j.critrevonc.2018.09.004"}],"container-title":["Radiation Research"],"original-title":[],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:04:20Z","timestamp":1791234260000},"score":1,"resource":{"primary":{"URL":"https:\/\/bioone.org\/journals\/radiation-research\/volume-205\/issue-5\/RADE-25-00117.1\/Apigenin-Enhances-the-Radiosensitivity-of-TNBC-Cells-by-Improving-cGAS\/10.1667\/RADE-25-00117.1.full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,10]]},"references-count":39,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5,1]]}},"URL":"https:\/\/doi.org\/10.1667\/rade-25-00117.1","relation":{},"ISSN":["0033-7587","1938-5404"],"issn-type":[{"value":"0033-7587","type":"print"},{"value":"1938-5404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,10]]}}}