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    Article

    Luteolin-Zinc Modulates PRR11 Methylation and Ferroptosis in Lung Cancer Cells Under Hypoxia

    Jiayong Huang1, Binbo Fang2, Ting Guo2, Yiyang Li2★, Yilin Yang2, Jiongcheng Ying2, Haoyun Zhou2, Xiang Li1★ Corresponding author

    1. 1Department of Respiratory Medicine, Yuhuan Second People’s Hospital, Yuhuan, Taizhou, CHINA.
    2. 2Department of Medicine, Taizhou University, Jiaojiang, Zhejiang, China.

    CORRESPONDENCE

    Yiyang Li

    Department of Medicine, Taizhou University, Jiaojiang, Zhejiang, China.

    q642535852@163.com

    Received: 06-08-2024; Accepted: 16-12-2024.

    Volume 21, Issue 3 · pp. 895–905 · PUBLISHED 2025 · DOI: 10.1177/09731296241311343

    View on Pharmacogn. Mag. original site ↗

    ABSTRACT

    Background: Activation of PRR11 contributes to the progression of lung cancer and is related to its methylation status. However, the regulatory mechanism of luteolin-zinc (Lu-Zn) on PRR11 methylation-mediated lung cancer progression under hypoxic conditions remains to be explored. Objectives: This study aims to investigate the inhibitory effect of Lu-Zn on lung cancer cells, its regulation of ferroptosis, and the role of PRR11 in lung cancer progression under hypoxia. Materials and Methods: In vitro experiments were conducted to evaluate the effect of Lu-Zn on lung cancer cells, focusing on its impact on invasion, migration, and ferroptosis. The expression levels of PRR11, its methylation status, and microRNA- 6769b-3p (miR-6769b-3p) were also analyzed. Results: Under hypoxic conditions, Lu-Zn significantly inhibited the invasion and migration abilities of lung cancer cells and promoted ferroptosis. Additionally, Lu-Zn reversed the pro-cancer effects induced by PRR11. At the molecular level, Lu-Zn promoted the methylation of PRR11 and regulated miR-6769b-3p. Conclusion: Our study demonstrates that Lu-Zn enhances the methylation of PRR11 and reduces its expression under hypoxic conditions through miR-6769b-3p. This leads to inhibition of the downstream PI3K/AKT/mTOR signaling pathway, promoting ferroptosis and exerting anti-lung cancer effects.

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      Huang, J., Fang, B., Guo, T., Li, Y., Yang, Y., Ying, J., Zhou, H., & Li, X. (2025). Luteolin-Zinc Modulates PRR11 Methylation and Ferroptosis in Lung Cancer Cells Under Hypoxia. Pharmacognosy Magazine, 21(3), 895–905. https://doi.org/10.1177/09731296241311343