Clostridium scindens metabolites trigger prostate cancer progression through androgen receptor signaling |
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| Institution: | 1. Graduate Institute of Biomedical Sciences, Department of Microbiology and Immunology, Department of Biochemistry, Chang Gung University, Taoyuan, Taiwan;2. Faculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho, Viet Nam;3. Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan;4. Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA;5. Kidney Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan;6. Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan;7. Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan;8. Department of Medical Research, School of Medicine, China Medical University and Hospital, Taichung, Taiwan;9. Department of Nursing, Asia University, Taichung, Taiwan;10. Molecular Infectious Disease Research Center, Department of Pediatrics, Chang Gung Memorial Hospital, Linkou, Taiwan |
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| 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. |
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| Keywords: | Bacterial metabolite Prostate cancer Androgen |
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