2. Academic Validation
  3. Microbially produced imidazole propionate impairs prostate cancer progression through PDZK1

Microbially produced imidazole propionate impairs prostate cancer progression through PDZK1

  • Mol Med. 2025 Jan 16;31(1):14. doi: 10.1186/s10020-025-01073-0.
Shengkai Jin # 1 2,  Yuhua Zhou # 1 2,  Jing Lv # 1 2,  Yichen Lu 3 2,  Yuwei Zhang 4 5,  Menglu Li 6,  Ninghan Feng 7 8 9
Affiliations

Affiliations

  • 1 Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China.
  • 2 Department of Urology, Jiangnan University Medical School, Jiangnan University Medical Center (Wuxi No. 2 People's Hospital), 68 Zhongshan Road, Wuxi, 214002, Jiangsu, China.
  • 3 Nanjing Medical University, Nanjing, 211166, China.
  • 4 Nantong University Medical School, 9 Qiangyuan Road, Nantong, 226019, China. zhangyw0123@njmu.edu.cn.
  • 5 Department of Urology, Jiangnan University Medical School, Jiangnan University Medical Center (Wuxi No. 2 People's Hospital), 68 Zhongshan Road, Wuxi, 214002, Jiangsu, China. zhangyw0123@njmu.edu.cn.
  • 6 Department of Urology, Jiangnan University Medical School, Jiangnan University Medical Center (Wuxi No. 2 People's Hospital), 68 Zhongshan Road, Wuxi, 214002, Jiangsu, China. lmlbw1232@163.com.
  • 7 Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China. n.feng@jiangnan.edu.cn.
  • 8 Nantong University Medical School, 9 Qiangyuan Road, Nantong, 226019, China. n.feng@jiangnan.edu.cn.
  • 9 Department of Urology, Jiangnan University Medical School, Jiangnan University Medical Center (Wuxi No. 2 People's Hospital), 68 Zhongshan Road, Wuxi, 214002, Jiangsu, China. n.feng@jiangnan.edu.cn.
  • # Contributed equally.
PMID: 39819421 DOI: 10.1186/s10020-025-01073-0
Abstract

Background: A close relationship exists between castration-resistant prostate Cancer (CRPC) and histidine metabolism by gut microbes. However, the effects of the histidine metabolite imidazole propionate (IMP) on prostate Cancer (PCa) and its underlying mechanisms are not well understood.

Methods: We first assessed the effects of IMP on cell proliferation and migration at the cellular level. Subsequently, we investigated the mechanism of action of IMP using transcriptome Sequencing, qPCR, and Western blot analysis. Finally, we validated our findings in vivo using a mouse model.

Results: Histidine had no effect on PCa cell proliferation; however, IMP significantly inhibited the proliferation and migration of PC3 and DU145 cells. Mechanistic studies indicate that IMP exerts its effects by upregulating PDZK1 expression, which subsequently inhibits the phosphorylation of the PI3K-AKT pathway.

Conclusions: In conclusion, IMP significantly inhibits the progression of PCa, offering new insights into potential treatments for CRPC.

Keywords

Castration-resistant prostate cancer; Histidine; Imidazole propionate; Microbiome; Prostate cancer.

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