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Open AccessArticle

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

1
Department of Biomolecular Pharmacology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan
2
Department of Clinical Pharmacokinetics, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan
3
Division of Pharmacology, Faculty of Pharmaceutical Sciences, Teikyo Heisei University, 4-21-2 Nakano, Nakano-ku, Tokyo 164-8530, Japan
4
Department of Clinical Pharmaceutics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan
5
Department of Functional Molecular Kinetics, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this paper.
Biomedicines 2020, 8(7), 180; https://doi.org/10.3390/biomedicines8070180
Received: 11 June 2020 / Revised: 24 June 2020 / Accepted: 25 June 2020 / Published: 27 June 2020
(This article belongs to the Special Issue Natural Medicine in Therapy)
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. View Full-Text
Keywords: ergosterol; cyclin D1; androgen receptor; 5α-reductase; bladder cancer ergosterol; cyclin D1; androgen receptor; 5α-reductase; bladder cancer
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Ikarashi, N.; Hoshino, M.; Ono, T.; Toda, T.; Yazawa, Y.; Sugiyama, K. A Mechanism by which Ergosterol Inhibits the Promotion of Bladder Carcinogenesis in Rats. Biomedicines 2020, 8, 180.

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