Microbially produced imidazole propionate impairs prostate cancer progression through PDZK1
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. Me...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
|
| Series: | Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s10020-025-01073-0 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832594647905468416 |
|---|---|
| author | Shengkai Jin Yuhua Zhou Jing Lv Yichen Lu Yuwei Zhang Menglu Li Ninghan Feng |
| author_facet | Shengkai Jin Yuhua Zhou Jing Lv Yichen Lu Yuwei Zhang Menglu Li Ninghan Feng |
| author_sort | Shengkai Jin |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-bfe83bc47316435890fb62089924f909 |
| institution | Kabale University |
| issn | 1528-3658 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj-art-bfe83bc47316435890fb62089924f9092025-01-19T12:27:22ZengBMCMolecular Medicine1528-36582025-01-0131111410.1186/s10020-025-01073-0Microbially produced imidazole propionate impairs prostate cancer progression through PDZK1Shengkai Jin0Yuhua Zhou1Jing Lv2Yichen Lu3Yuwei Zhang4Menglu Li5Ninghan Feng6Wuxi School of Medicine, Jiangnan UniversityWuxi School of Medicine, Jiangnan UniversityWuxi School of Medicine, Jiangnan UniversityNanjing Medical UniversityNantong University Medical SchoolDepartment of Urology, Jiangnan University Medical School, Jiangnan University Medical Center (Wuxi No. 2 People’s Hospital)Wuxi School of Medicine, Jiangnan UniversityAbstract 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.https://doi.org/10.1186/s10020-025-01073-0Imidazole propionateHistidineProstate cancerMicrobiomeCastration-resistant prostate cancer |
| spellingShingle | Shengkai Jin Yuhua Zhou Jing Lv Yichen Lu Yuwei Zhang Menglu Li Ninghan Feng Microbially produced imidazole propionate impairs prostate cancer progression through PDZK1 Molecular Medicine Imidazole propionate Histidine Prostate cancer Microbiome Castration-resistant prostate cancer |
| title | Microbially produced imidazole propionate impairs prostate cancer progression through PDZK1 |
| title_full | Microbially produced imidazole propionate impairs prostate cancer progression through PDZK1 |
| title_fullStr | Microbially produced imidazole propionate impairs prostate cancer progression through PDZK1 |
| title_full_unstemmed | Microbially produced imidazole propionate impairs prostate cancer progression through PDZK1 |
| title_short | Microbially produced imidazole propionate impairs prostate cancer progression through PDZK1 |
| title_sort | microbially produced imidazole propionate impairs prostate cancer progression through pdzk1 |
| topic | Imidazole propionate Histidine Prostate cancer Microbiome Castration-resistant prostate cancer |
| url | https://doi.org/10.1186/s10020-025-01073-0 |
| work_keys_str_mv | AT shengkaijin microbiallyproducedimidazolepropionateimpairsprostatecancerprogressionthroughpdzk1 AT yuhuazhou microbiallyproducedimidazolepropionateimpairsprostatecancerprogressionthroughpdzk1 AT jinglv microbiallyproducedimidazolepropionateimpairsprostatecancerprogressionthroughpdzk1 AT yichenlu microbiallyproducedimidazolepropionateimpairsprostatecancerprogressionthroughpdzk1 AT yuweizhang microbiallyproducedimidazolepropionateimpairsprostatecancerprogressionthroughpdzk1 AT mengluli microbiallyproducedimidazolepropionateimpairsprostatecancerprogressionthroughpdzk1 AT ninghanfeng microbiallyproducedimidazolepropionateimpairsprostatecancerprogressionthroughpdzk1 |