{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T10:05:27Z","timestamp":1779444327071,"version":"3.53.1"},"reference-count":38,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hematologic malignancies are driven by dysregulated growth and survival signaling pathways that promote proliferation, treatment resistance, and disease progression. Naturally derived compounds targeting multiple oncogenic pathways with low toxicity have gained interest. Apigenin, a dietary flavonoid, shows anticancer activity in solid tumors, but its molecular effects in hematologic malignancies remain unclear. The antineoplastic effects of apigenin were evaluated in K562 (chronic myeloid leukemia) and DOHH2 (B-cell lymphoma) cell lines. Cell viability was assessed using the CCK-8 assay. L929 (mouse fibroblast) cells were included to evaluate selectivity. EGFR, MAPK, PI3K, NF-\u03baB, caspase-3, and caspase-7 levels were measured by ELISA. Apoptosis and cell cycle distribution were analyzed by flow cytometry. Apigenin reduced cell viability in a dose-dependent manner, with IC50 values of 84.14 \u03bcM (K562) and 70.11 \u03bcM (DOHH2). It suppressed EGFR, MAPK, PI3K, and NF-\u03baB signaling and increased the caspase-3 and caspase-7 levels (p &lt; 0.001). Flow cytometry showed S-phase arrest and increased apoptosis. L929 cells showed limited reduction in viability at higher concentrations. Apigenin exerts antiproliferative and pro-apoptotic effects via inhibition of the EGFR\/MAPK and PI3K\/Akt pathways and activation of caspase-mediated apoptosis. Lower sensitivity in L929 cells suggests relative selectivity, supporting further in vivo and clinical studies.<\/jats:p>","DOI":"10.3390\/ijms27114657","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T09:17:09Z","timestamp":1779441429000},"page":"4657","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Apigenin as a Multitarget Anticancer Agent: Coordinated Inhibition of EGFR\/MAPK and PI3K\/Akt Signaling in Hematologic Malignancies"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3471-1305","authenticated-orcid":false,"given":"Hatice","family":"Terzi","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Department of Hematology, Faculty of Medicine, Sivas Cumhuriyet University, 58140 Sivas, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u015eeyma","family":"Ta\u015ftemur","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, Sivas Cumhuriyet University, 58140 Sivas, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ay\u015feg\u00fcl","family":"\u00d6zt\u00fcrk","sequence":"additional","affiliation":[{"name":"Department of Therapy and Rehabilitation, Vocational School of Health Services, Sivas Cumhuriyet University, 58140 Sivas, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neslihan","family":"Ba\u015fg\u00f6z Karagu\u015f","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine, Erciyes University, 38280 Kayseri, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4487-4219","authenticated-orcid":false,"given":"Mustafa Eymen","family":"Konta\u015f","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Department of Hematology, Faculty of Medicine, Sivas Cumhuriyet University, 58140 Sivas, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onur","family":"Mahmuto\u011flu","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Sivas Provincial Health Directorate, 58080 Sivas, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7985-0986","authenticated-orcid":false,"given":"Ali","family":"G\u00fcng\u00f6r","sequence":"additional","affiliation":[{"name":"Laboratory and Veterinary Health Program, Health Services Vocational School, Osmaniye Korkut Ata University, 80000 Osmaniye, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet","family":"\u015eencan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Department of Hematology, Faculty of Medicine, Sivas Cumhuriyet University, 58140 Sivas, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100825","DOI":"10.1016\/j.blre.2021.100825","article-title":"Chronic Myeloid Leukemia: Modern therapies, current challenges and future directions","volume":"49","author":"Osman","year":"2021","journal-title":"Blood Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1001\/jama.2025.0220","article-title":"Chronic myeloid leukemia: A review","volume":"333","author":"Jabbour","year":"2025","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s11899-023-00703-w","article-title":"Real-world management of CML: Outcomes and treatment patterns","volume":"18","author":"Held","year":"2023","journal-title":"Curr. 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Vitr."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/4657\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T09:21:54Z","timestamp":1779441714000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/4657"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,22]]},"references-count":38,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27114657"],"URL":"https:\/\/doi.org\/10.3390\/ijms27114657","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,22]]}}}