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ORIGINAL RESEARCH article

Front. Pharmacol.

Sec. Pharmacology of Anti-Cancer Drugs

Volume 16 - 2025 | doi: 10.3389/fphar.2025.1584376

This article is part of the Research TopicNovel Targets and Therapeutic Strategies for Overcoming Drug Resistance in Hematologic MalignanciesView all 4 articles

FGFC1 overcomes Ara-C resistance in acute myeloid leukemia by inducing apoptosis and pyroptosis

Provisionally accepted
Xiaohui  HuXiaohui Hu1Zhijian  LiZhijian Li1Rui  ZhouRui Zhou1Bing  ZhangBing Zhang1Ruoxian  WangRuoxian Wang1Tongtong  LiTongtong Li1Jiangcheng  ChangJiangcheng Chang1Wenhui  WuWenhui Wu1,2*Ning  LiuNing Liu1,2,3,4*
  • 1International Research Centre for Food and Health, College of Food Science and Technology, Shanghai Ocean University, Shanghai, China
  • 2Department of Chemistry, College of Food Science and Technology, Shanghai Ocean University, Shanghai, China
  • 3Marine Biomedical Science and Technology Innovation Platform of Lin-gang Special Area, Shanghai, China
  • 4Shanghai Engineering Research Center of Aquatic-Product Processing & Preservation, Shanghai, China

The final, formatted version of the article will be published soon.

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 Stachybotrys longispora 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.

Keywords: acute myeloid leukemia (AML), Cytarabine (Ara-C) resistance, FGFC1, Apoptosis and pyroptosis, GSDME

Received: 27 Feb 2025; Accepted: 31 Jul 2025.

Copyright: © 2025 Hu, Li, Zhou, Zhang, Wang, Li, Chang, Wu and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Wenhui Wu, International Research Centre for Food and Health, College of Food Science and Technology, Shanghai Ocean University, Shanghai, China
Ning Liu, International Research Centre for Food and Health, College of Food Science and Technology, Shanghai Ocean University, Shanghai, China

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