Exploring the mechanism of action of glaucocalyxin D against acute myeloid leukemia using network pharmacology, molecular docking and cellular experiments
Year: 2026
Type: article
Abstract: Glaucocalyxin D (GLD), an ent-kaurane diterpenoid isolated from Isodon species, exhibits extensive pharmacological potential; however, its mechanism of action against acute myeloid leukemia (AML) remains to be elucidated.The present study employed a combined network pharmacology and experimental approach to elucidate the anti-AML mechanisms of GLD.Potential targets were identified using database mining and a protein-protein interaction network was constructed.The Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes enrichment analyses highlighted the JAK-STAT signaling pathway as central to action by GLD.Molecular docking predicted stable binding of GLD to core targets, including STAT3.Experimental validation in HEL and K562 AML cells demonstrated that GLD potently and dose-dependently inhibits cell proliferation, with efficacy similar to the standard chemotherapeutic agent doxorubicin.Mechanistically, GLD suppressed the phosphorylation of JAK2 and STAT3.GLD also induced mitochondrial apoptosis by modulating the Bcl-2/Bax ratio and triggered G 2 /M phase arrest by downregulating cyclin B1 and CDK1.These findings delineated a coherent mechanism whereby GLD exerts anti-leukemic effects by inhibiting the JAK-STAT pathway, supporting its potential as a novel lead compound for AML therapy in the future.
Source: Oncology Letters
Authors: Lian Chen, Weixian Yang, Weiqing Zhang, Heng Luo, Chen Yan
Institution: Guiyang Medical University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W7155827993
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