Ganoderic Acid A Suppresses Androgenindependent Cell Growth via the AKT/GSK-3β/β-catenin Signaling Pathway
Qiao Lyu1, Yuan Qu1, Jianfan Chen1, Guo Chen1, Zheng Chen1★, Lijun Qu1★★ Corresponding author
- 1Department of Urology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong Province, China.
CORRESPONDENCE
Zheng Chen
Department of Urology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong Province, China.
Received: 20-01-2024; Accepted: 13-05-2024.
Volume 21, Issue 2 · pp. 467–479 · PUBLISHED 2025 · DOI: 10.1177/09731296241262075
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ABSTRACT
Objectives: The primary aim of this study is to investigate the specific effects and mechanisms of ganoderic acid A (GAA) on castration-resistant prostate cancer (CRPC). Materials and Methods: We successfully established an androgen-independent prostate cancer cell line (LNCaP-AI). The LNCaP-AI cells demonstrated accelerated growth, elevated levels of androgen receptor and prostate-specific antigen (PSA), and resistance to the drug enzalutamide. Then, we administered LNCaP-AI cells with GAA or a control and determined the cell growth rate. Next, LNCaP-AI cells with and without GAA treatment were subjected to RNA-seq for mRNA sequencing. The genes were subjected to a Kyoto Encyclopedia of Genes and Genomes analysis. We also checked the expression levels of the targeted genes. Finally, normal LNCaP or LNCaP-AI cells were subcutaneously injected into nude mice to further confirm the effect of GAA. Results: Experiments showed that GAA effectively suppressed the growth rate, PSA secretion, migration, and invasion of LNCaP-AI cells. The results of a subsequent RNA-seq analysis identified the PI3K/AKT pathway as the key signaling pathway influenced by GAA. Notably, AKT and GSK-3β phosphorylation was decreased, and β-catenin protein levels were also lowered, as a result of GAA treatment. Moreover, we observed decreased activity in crucial genes, including c-Myc, Cyclin D1, and MMP-2, which play integral roles in CRPC development. Furthermore, GAA inhibited the tumorigenesis of LNCaP-AI cells in nude mice in vivo. Conclusion: GAA effectively suppresses the growth of androgen-independent cells by inhibiting the AKT/GSK-3β/β-catenin signaling pathway. These findings demonstrate the potential of GAA as a therapeutic candidate for CRPC.
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Lyu, Q., Qu, Y., Chen, J., Chen, G., Chen, Z., & Qu, L. (2025). Ganoderic Acid A Suppresses Androgenindependent Cell Growth via the AKT/GSK-3β/β-catenin Signaling Pathway. Pharmacognosy Magazine, 21(2), 467–479. https://doi.org/10.1177/09731296241262075