{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T03:24:27Z","timestamp":1784690667903,"version":"3.55.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T00:00:00Z","timestamp":1755129600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Acute myeloid leukemia (AML) is a hematologic malignancy with a high mortality rate and poor prognosis, largely attributed to the emergence of chemotherapy resistance. Cytarabine (Ara-C), the cornerstone chemotherapeutic agent for AML, faces significant challenges due to the development of resistance, creating an urgent need for novel therapeutic strategies. Pyroptosis as a new form of programmed cell death has emerged as a potential therapeutic target in tumor treatment. However, its role in overcoming Ara-C resistance in AML by modulating pyroptosis remains unexplored. FGFC1 (Fungi fibrinolytic compound 1) a natural compound derived from <jats:italic>Stachybotrys longispora<\/jats:italic> FG216, has previously been shown to have high efficacy against erlotinib-resistant non-small cell lung cancer, yet its effects on AML are unknown. This study demonstrated that FGFC1 overcame Ara-C resistance in AML by inducing apoptosis and pyroptosis. Mechanistically, FGFC1 induced mitochondrial dysfunction and the accumulation of intracellular reactive oxygen species (ROS), leading to the release of cytochrome c (Cyto-C), which activated Caspase-3 and triggered both apoptosis and pyroptosis. This process was driven by inhibition of the PI3K\/Akt\/mTOR signaling cascade, ultimately suppressing the growth of AML Ara-C-resistant cells. These findings highlight the potential of FGFC1 to overcome Ara-C resistance in AML, providing a promising therapeutic strategy for drug-resistant AML and supporting the broader application of marine-derived small molecules in cancer therapy.<\/jats:p>","DOI":"10.3389\/fphar.2025.1584376","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T05:34:44Z","timestamp":1755149684000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["FGFC1 overcomes Ara-C resistance in acute myeloid leukemia by inducing apoptosis and pyroptosis"],"prefix":"10.3389","volume":"16","author":[{"given":"Xiaohui","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijian","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoxian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongtong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangcheng","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1038\/s41423-020-00630-3","article-title":"Necroptosis, pyroptosis and apoptosis: an intricate game of cell death","volume":"18","author":"Bertheloot","year":"2021","journal-title":"Cell. and Mol. 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