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Planta Med
DOI: 10.1055/a-2816-0955
Original Papers

Oleandrin Suppresses the PI3K/AKT Pathway to Inhibit Growth and Induce Apoptosis in T-cell Acute Lymphoblastic Leukemia Cells and Xenograft Mice

Authors

  • Haihui Zhuang

    1   School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China
    2   Department of Hematology, The Affiliated Peopleʼs Hospital of Ningbo University, Ningbo, China

  • Xia Jiang

    2   Department of Hematology, The Affiliated Peopleʼs Hospital of Ningbo University, Ningbo, China
    3   Institute of Hematology, Ningbo University, Ningbo, China

  • Fenglin Li

    2   Department of Hematology, The Affiliated Peopleʼs Hospital of Ningbo University, Ningbo, China
    3   Institute of Hematology, Ningbo University, Ningbo, China

  • Wenjie Sha

    2   Department of Hematology, The Affiliated Peopleʼs Hospital of Ningbo University, Ningbo, China
    3   Institute of Hematology, Ningbo University, Ningbo, China

  • Ying Lu 

    2   Department of Hematology, The Affiliated Peopleʼs Hospital of Ningbo University, Ningbo, China
    3   Institute of Hematology, Ningbo University, Ningbo, China

This study was funded by the Natural Science Foundation of Zhejiang (LQN25H080005), Zhejiang Provincial Traditional Chinese Medicine Science and Technology Project (22025ZL124), and the Science and Technology Project of Agriculture and Social Science of Ningbo Yinzhou District (2022AS017).
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Abstract

T-cell acute lymphoblastic leukemia (T-ALL) remains a clinical challenge due to its high relapse rate and limited treatment options. This study aimed to investigate the cytotoxic effects of oleandrin on T-ALL and its underlying mechanism to explore novel therapeutic strategies. In human T-ALL cell lines, it inhibited cell growth and induced apoptosis in a dose- and time-dependent manner, with half-maximal inhibitory concentration (IC₅₀) values ranging from 16 to 31 nM. In mouse xenograft models, oleandrin reduced tumor burden and prolonged survival without significant toxicity. Integrated mechanistic studies, including network pharmacology, transcriptomics, and Western blot analysis, indicated that the anti-leukemic effects of oleandrin are associated with suppression of the PI3K/AKT signaling pathway, as evidenced by reduced levels of key proteins such as PIK3CA, phosphorylated AKT (p-AKT), phosphorylated GSK3β (p-GSK3β), c-Myc, Bcl-2, and Bcl-xL. These findings suggest oleandrin is a promising therapeutic candidate for T-ALL, likely through suppression of the PI3K/AKT pathway.

Keywords

oleandrin - Nerium oleander - Apocynaceae - T-cell acute lymphoblastic leukemia - PI3K/AKT pathway - apoptosis

Supporting Information



Publication History

Received: 22 October 2025

Accepted after revision: 17 February 2026

Article published online:
05 March 2026

© 2026. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 14, 70469 Stuttgart, Germany

 

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