Articles
Vol. 70 No. 3 (2026)
https://doi.org/10.4081/ejh.2026.4575

Mechanism of lovastatin in promoting ferroptosis of prostate cancer cells by regulating the mevalonate pathway

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Published: 23 July 2026
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Prostate cancer, lovastatin, MVA pathway, ferroptosis

Authors

Yanhong Xiao
Department of Urology, Affiliated Hospital of Zunyi Medical University, China.
Zhengdao Liu
Department of Urology, Affiliated Hospital of Zunyi Medical University, China.
Yougang Feng
Department of Urology, Suining Central Hospital, China.
Han Zhu
Department of Urology, Affiliated Hospital of Zunyi Medical University, China.
Bo Wang
Department of Urology, Affiliated Hospital of Zunyi Medical University, China.
Shulian Chen
Department of Urology, Affiliated Hospital of Zunyi Medical University, China.
Guobiao Liang
lgb11112021@163.com
Department of Urology, Affiliated Hospital of Zunyi Medical University, China.

Prostate cancer (PCa) is a common malignancy in men with limited therapeutic options at advanced stages. Statins, widely prescribed lipid-lowering agents, have demonstrated antitumor activity in PCa, but underlying mechanisms are not fully understood. Studies suggested that tumor progression is facilitated upon activation of mevalonate (MVA) pathway, while it is reduced via MVA pathway inhibition–induced ferroptosis. Therefore, this study aimed to determine whether lovastatin suppresses prostate cancer progression by inducing ferroptosis through inhibition of the MVA pathway. Five clinically used statins were screened in prostate cancer cell lines to identify the most effective compound. Cell proliferation, migration, and invasion were assessed. Ferroptosis was evaluated by measuring intracellular Fe2+ and reactive oxygen species (ROS) levels, mitochondrial membrane potential, ferroptosis-related protein expression, and ultrastructural mitochondrial alterations. Rescue experiments were performed using the ferroptosis inhibitor deferoxamine and MVA supplementation. Lovastatin exhibited the strongest inhibitory effect, significantly reducing proliferation, migration, and invasion. Lovastatin significantly suppressing PCa cell aggressiveness and inducing ferroptosis, as evidenced by typical biochemical and morphological markers, all of which were reversed by deferoxamine. MVA supplementation restored cell viability, normalized oxidative stress and iron levels, and reversed alterations in MVA pathway enzymes and ferroptosis-associated proteins. Lovastatin suppresses prostate cancer cell growth and invasiveness by inhibiting the MVA pathway and inducing ferroptosis, highlighting the MVA-ferroptosis axis as a potential therapeutic target for PCa.

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CRediT authorship contribution

Yanhong Xiao: conceptualization, methodology, investigation, data curation, formal analysis, writing-original draft. Zhengdao Liu, methodology, investigation, data curation, formal analysis, visualization. Yougang Feng, investigation, methodology, validation. Han Zhu: investigation, data curation. Bo Wang, investigation, resources. Shulian Chen, conceptualization, methodology, supervision, writing-review & editing, funding acquisition. Guobiao Liang, conceptualization, supervision, project administration, writing-review & editing, funding acquisition.
All authors read and approved the final manuscript for submission.

Supporting Agencies

Guizhou Province

Data Availability Statement

The datasets used and analysed in the current study are available from the corresponding author upon reasonable request.

How to Cite



1.
Xiao Y, Liu Z, Feng Y, Zhu H, Wang B, Chen S, et al. Mechanism of lovastatin in promoting ferroptosis of prostate cancer cells by regulating the mevalonate pathway. Eur J Histochem [Internet]. 2026 Jul. 23 [cited 2026 Jul. 24];70(3). Available from: https://www.ejh.it/ejh/article/view/4575
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