Berberine triggers apoptosis through the PI3K/Akt pathways and Nrf2 by inducing ROS in papillary thyroid cancer

Jing Li; Ziyi Zhu; Jing Ni; Lizi Ye; Xiaoyan Huang; Dong Jing; Yanhong Lu; Ling Yue

doi:10.1016/j.abb.2025.110481

Berberine triggers apoptosis through the PI3K/Akt pathways and Nrf2 by inducing ROS in papillary thyroid cancer

Arch Biochem Biophys. 2025 May 26:771:110481. doi: 10.1016/j.abb.2025.110481. Online ahead of print.

Authors

Jing Li¹, Ziyi Zhu², Jing Ni³, Lizi Ye⁴, Xiaoyan Huang¹, Dong Jing⁴, Yanhong Lu⁴, Ling Yue⁵

Affiliations

¹ Department of Endocrinology, The General Hospital of Central Theater Command, Wuhan, 430070, China; The First School of Clinical Medicine, Southern Medical University, Guangzhou, 510180, China.
² Suzhou Xiangcheng District Integrated Chinese and Western Medicine Hospital, Suzhou 215137, Jiangsu, China.
³ Department of Endocrinology, Nanjing Jiang Ning Hospital of Traditional Chinese Medicine, Nanjing, 211100, China.
⁴ Department of Endocrinology, The General Hospital of Central Theater Command, Wuhan, 430070, China.
⁵ Department of Endocrinology, The General Hospital of Central Theater Command, Wuhan, 430070, China; The First School of Clinical Medicine, Southern Medical University, Guangzhou, 510180, China. Electronic address: yuelingwh@163.com.

PMID: 40436359
DOI: 10.1016/j.abb.2025.110481

Abstract

Background: Nrf2 is highly expressed in papillary thyroid cancer (PTC) and is associated with negative outcomes. Research has indicated that Berberine (BBR) can lower Nrf2 levels and trigger apoptosis in cancer cells. However, the exact molecular mechanisms behind its anticancer effects in PTC are not fully understood.

Methods: The effects of BBR on cell apoptosis were assessed using the MTT assay and flow cytometry. To evaluate BBR's in vivo antitumor efficacy, a xenograft model was used. Molecular and biochemical methods were applied to clarify the mechanisms through which BBR exerts its anticancer effects in PTC.

Results: BBR has been shown to effectively inhibit the growth of PTC cells and promote programmed cell death. A higher dose of BBR administered via gavage significantly reduced the development of xenograft tumors. Mechanistically, BBR inhibits the Nrf2-dependent pathway of PI3K/Akt signaling pathway, resulting in the production of reactive oxygen species (ROS).

Conclusions: Our results suggest indicate that BBR can target PTC by inhibiting the Nrf2 and PI3K/Akt pathways through ROS generation. This indicats that BBR may serve as a potential therapeutic agent for PTC treatment.

Keywords: Berberine; Nuclear factor E2 p45-related factor 2 (Nrf2); PI3K/Akt; Papillary thyroid cancer; ROS.