A Mechanism by which Ergosterol Inhibits the Promotion of Bladder Carcinogenesis in Rats.

Nobutomo Ikarashi,Yasuharu Yazawa,Tetsuya Ono,Takahiro Toda,Kiyoshi Sugiyama,Motohiro Hoshino

doi:10.3390/biomedicines8070180

Nobutomo Ikarashi, Yasuharu Yazawa + Show 4 more

Open Access

https://doi.org/10.3390/biomedicines8070180

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Abstract

We previously showed that ergosterol has an inhibitory effect on bladder carcinogenesis. In this study, we aimed to elucidate the molecular mechanism by which ergosterol inhibits bladder carcinogenesis using a rat model of N-butyl-N-(4-hydroxybutyl)nitrosamine-induced bladder cancer. The messenger ribonucleic acid (mRNA) expression level of the cell cycle-related gene cyclin D1 and inflammation-related gene cyclooxygenase-2 in bladder epithelial cells was significantly increased in the carcinogenesis group compared with the control group. In contrast, in ergosterol-treated rats, these increases were significantly suppressed. Ergosterol did not affect the plasma testosterone concentration or the binding of dihydrotestosterone to androgen receptor (AR). The mRNA expression levels of 5α-reductase type 2 and AR were higher in the carcinogenesis group than in the control group but were significantly decreased by ergosterol administration. These results suggest that ergosterol inhibits bladder carcinogenesis by modulating various aspects of the cell cycle, inflammation-related signaling, and androgen signaling. Future clinical application of the preventive effect of ergosterol on bladder carcinogenesis is expected.

Highlights

Bladder cancer is one of the most common urological tumors
The inhibitory effect of ergosterol on bladder carcinogenesis was examined in a short-term carcinogenicity study using SS as the promoter [10,12] and evaluated in a Concanavalin A (Con A) agglutination assay
Strongly inhibits the promotion of bladder carcinogenesis [10] and that long-term administration of ergosterol reduces the incidence of carcinogenesis [11]

Summary

Introduction

Bladder cancer is one of the most common urological tumors. It mainly affects men, with an incidence approximately 10 times higher in men than in women [1]. 70% of bladder cancers are non-muscle-invasive, and transurethral resection (TUR) is a common treatment. Treatment with anticancer agents [3,4] and bacillus Calmette-Guérin (BCG) infusion [5,6] into the bladder are performed after TUR. These treatments impose both a heavy burden on the patient and a large economic burden [7]. A new preventive method that can solve these problems is strongly desired

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