Clostridium scindens metabolites trigger prostate cancer progression through androgen receptor signaling

Ngoc Niem Bui, Chen Yi Li, Ling Yu Wang, Yu An Chen, Wei Hsiang Kao, Li Fang Chou, Jer Tsong Hsieh, Ho Lin, Chih Ho Lai*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

4 Scopus citations

Abstract

Prostate cancer (PCa) is one of the most common malignancies in men; recently, PCa-related mortality has increased worldwide. Although androgen deprivation therapy (ADT) is the standard treatment for PCa, patients often develop aggressive castration-resistant PCa (CRPC), indicating the presence of an alternative source of androgen. Clostridium scindens is a member of the gut microbiota and can convert cortisol to 11β-hydroxyandrostenedione (11β-OHA), which is a potent androgen precursor. However, the effect of C. scindens on PCa progression has not been determined. In this study, androgen-dependent PCa cells (LNCaP) were employed to investigate whether C. scindens-derived metabolites activate androgen receptor (AR), which is a pivotal step in the development of PCa. Results showed that cortisol metabolites derived from C. scindens-conditioned medium promoted proliferation and enhanced migration of PCa cells. Furthermore, cells treated with these metabolites presented activated AR and stimulated AR-regulated genes. These findings reveal that C. scindens has the potential to promote PCa progression via the activation of AR signaling. Further studies on the gut–prostate axis may help unravel an alternative source of androgen that triggers CRPC exacerbation.

Original languageEnglish
Pages (from-to)246-256
Number of pages11
JournalJournal of Microbiology, Immunology and Infection
Volume56
Issue number2
DOIs
StatePublished - 04 2023

Bibliographical note

Copyright © 2023. Published by Elsevier B.V.

Keywords

  • Androgen
  • Bacterial metabolite
  • Clostridium scindens
  • Prostate cancer
  • Androgens/metabolism
  • Hydrocortisone/metabolism
  • Humans
  • Male
  • Prostate/metabolism
  • Receptors, Androgen/genetics
  • Androgen Antagonists/metabolism
  • Cell Line, Tumor
  • Prostatic Neoplasms, Castration-Resistant/genetics

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