2. Academic Validation
  3. The PPARβ/CERK/C1P signaling pathway is a potential mechanism by which antimony exposure promotes prostate cancer cell proliferation

The PPARβ/CERK/C1P signaling pathway is a potential mechanism by which antimony exposure promotes prostate cancer cell proliferation

  • Ecotoxicol Environ Saf. 2025 Jun 1:297:118268. doi: 10.1016/j.ecoenv.2025.118268.
Jianxi Shi 1,  Zhaopeng Li 2,  Xiaoyu Sun 3,  Duo Zhao 4,  Shaosan Kang 5,  Fenghong Cao 6,  Zhihong Zhang 7,  Changwen Zhang 8
Affiliations

Affiliations

  • 1 Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China. Electronic address: stonejx2020@163.com.
  • 2 Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China. Electronic address: qddxlzp6@163.com.
  • 3 Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China. Electronic address: sunxiaoyu@tmu.edu.cn.
  • 4 Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China. Electronic address: tmuzhaoduo@163.com.
  • 5 Department of Urology, North China University of Science and Technology Affiliated Hospital, China. Electronic address: kangshaosan@sina.com.
  • 6 Department of Urology, North China University of Science and Technology Affiliated Hospital, China. Electronic address: caofenghong@ncst.edu.cn.
  • 7 Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China. Electronic address: zhangzhihongtianj@163.com.
  • 8 Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China. Electronic address: zhangchangwen05@tmu.edu.cn.
PMID: 40327927 DOI: 10.1016/j.ecoenv.2025.118268
Abstract

Prostate Cancer (PCa) is the most common malignant tumor in males. Antimony (Sb) is a widespread industrial heavy metal pollutant listed as a Class IIB carcinogen by the International Agency for Research on Cancer (IARC). Previous work found that antimony exposure can promote the proliferation of prostate Cancer cells, but the relevant molecular mechanisms have not been fully explored. Lipid metabolomic Sequencing revealed that ceramide levels were significantly elevated in PCa cells after low-dose antimony exposure. To explore the relationship between antimony exposure and cell proliferation, we found that the level of ceramide-1-phosphate (C1P), one of the metabolites of ceramide, increased after antimony exposure, and C1P can promote the proliferation of prostate Cancer cells and antagonize the Apoptosis induced by ceramide. Mechanism exploration shows that antimony exposure activates Peroxisome Proliferator-activated Receptor beta (PPARβ), up-regulates the expression levels of ceramide transport protein (CERT) and ceramide kinase (CERK), promotes the conversion of Cer to C1P, thereby inhibiting Apoptosis and promoting PCa cells proliferation. In addition, we also found that C1P can partially inhibit Ferroptosis induced by erastin. These findings indicate that C1P is closely related to antimony-induced PCa proliferation and may be a potential biomarker of PCa.

Keywords

Antimony; Ceramide; Ceramide 1-phosphate; Ferroptosis; Prostate cancer.

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