Mechanistic analysis of bladder cancer suppression by brassicasterol in a rat model of N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine‐induced bladder cancer

Abstract

Aim We previously clarified that the herbal medicine Polyporus Sclerotium, a constituent of Choreito, has an inhibitory effect on bladder carcinogenesis and that ergosterol is the active ingredient. In addition, we showed that this action of ergosterol may be caused by the metabolite brassicasterol. Here, we aimed to elucidate the detailed molecular mechanism by which brassicasterol inhibits bladder carcinogenesis. Methods A rat model of bladder cancer was established by feeding rats N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine (BHBN) and sodium saccharin (SS). After intraperitoneal administration of brassicasterol to rats, the mRNA expression levels of cell cycle‐related genes (cyclin D1, c‐fos, and c‐jun), inflammation‐related genes (cyclooxygenase‐2; COX‐2), and androgen signal‐related genes (5α‐reductase type 1; 5α‐R1, 5α‐reductase type 2; 5α‐R2, and the androgen receptor; AR) in bladder epithelial cells were analyzed. Results Brassicasterol significantly suppressed bladder carcinogenesis induced by BHBN and SS. The mRNA expression levels of cyclin D1 in bladder epithelial cells were significantly higher in the carcinogenesis group than in the control group. Additionally, the expression levels of c‐fos and c‐jun, constituents of the transcription factor activator protein‐1 (AP‐1) upstream of cyclin D1, were significantly increased in the carcinogenesis group compared with the control group. Moreover, the expression levels of COX‐2, 5α‐R1, 5α‐R2, and AR were significantly higher in the carcinogenesis group. In contrast, in rats treated with brassicasterol, the increases in the expression levels of these molecules were significantly suppressed. Conclusion We clarified that brassicasterol suppresses bladder carcinogenesis by acting on cell cycle‐related signaling, inflammation‐related signaling, and androgen signaling via multiple mechanisms.

In Silico Analysis of Metabolites from Peruvian Native Plants as Potential Therapeutics against Alzheimer’s Disease

“…Rutin has shown an inhibitory effect on α-glucosidase, effective for the treatment of diabetes [ 68 ], an antiviral effect on SARS-CoV-2 [ 69 ], and anti-inflammatory [ 70 ] and anticarcinogenic properties [ 71 ]. The sterol brassicasterol has shown a dual anti-infective property against herpes simplex virus type 1 and Mycobacterium tuberculosis [ 72 ], an antiviral effect against human adenovirus [ 73 ], and an anti-tumoral [ 74 ] and potential application as an AD biomarker [ 75 ]. For floribundic acid, besides its antioxidant effect, there is no other research based on the effects or bioactivity of this clerodane diterpenoid [ 76 ].…”