Open Access

ARTICLE

Apigenin facilitates apoptosis of acute lymphoblastic leukemia cells via AMP-activated protein kinase-mediated ferroptosis

by CANCAN HE^1,2,*, TINGTING ZHANG³, WEI XIONG⁴, SHENGYU WANG⁵, XIN SUN⁶

1 Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, China
2 Department of Pediatrics, Guizhou Children’s Hospital, Zunyi, 563003, China
3 Department of Radiology, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, China
4 Department of Cardiovascular Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, China
5 Key Laboratory of Infectious Disease & Biosafety, College of Preclinical Medicine, Zunyi Medical University, Zunyi, 563003, China
6 Department of Microbiology, College of Preclinical Medicine, Zunyi Medical University, Zunyi, 563003, China

* Corresponding Author: CANCAN HE. Email:

Oncology Research 2025, 33(2), 421-429. https://doi.org/10.32604/or.2024.049757

Received 17 January 2024; Accepted 07 April 2024; Issue published 16 January 2025

Abstract

Background: The outcomes of pediatric patients with acute lymphoblastic leukemia (ALL) remain far less than favorable. While apigenin is an anti-cancer agent, studies on the mechanism by which it regulates ALL cell cycle progression are inadequate. Ferroptosis and AMP-activated protein kinase (AMPK) signaling are important processes for ALL patients. However, it remains unclear whether apigenin works by affecting AMPK and apoptosis. Materials and Methods: SUP-B15 and T-cell Jurkat ALL cells were treated with apigenin, and cell viability and apoptosis were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays, respectively. The thiobarbituric acid-reactive substances (TBARS) assay was used to evaluate lipid peroxidation. Intracellular Fe²⁺ levels were measured using a commercial kit. Corresponding proteins were detected by western blotting. Results: Results showed that apigenin reduced cell viability and the levels of Ki67 and proliferating cell nuclear antigen (PCNA) expression in a concentration-dependent manner in both types of ALL cells. Apigenin also exerted anti-apoptotic effects on SUP-B15 and Jurkat cells. Apigenin activated AMP-activated protein kinase (AMPK) signaling and induced ferroptosis, and those effects were attenuated by inhibition of AMPK. Eventually, the reduced cell proliferation and increased cell apoptosis caused by apigenin in ALL cells were partly abolished by AMPK inhibition. Conclusion: In summary, apigenin exerted anti-leukemia activity in ALL cells, and that effect was partially achieved by activation of AMPK signaling. Our findings suggest apigenin as a potential drug for treatment of ALL.

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