Inhibitory effect of ergosterol on bladder carcinogenesis is due to androgen signaling inhibition by brassicasterol, a m
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ORIGINAL PAPER
Inhibitory effect of ergosterol on bladder carcinogenesis is due to androgen signaling inhibition by brassicasterol, a metabolite of ergosterol Yasuharu Yazawa1 · Nobutomo Ikarashi2 · Motohiro Hoshino3 · Hironori Kikkawa4 · Fumiyo Sakuma4 · Kiyoshi Sugiyama5 Received: 1 May 2020 / Accepted: 24 May 2020 © The Japanese Society of Pharmacognosy 2020
Abstract We previously revealed that Choreito, a traditional Kampo medicine, strongly inhibits bladder carcinogenesis promotion. We have also shown that Polyporus sclerotium, which is one of the crude drugs in Choreito, has the strongest bladder carcinogenesis inhibitory effect and that the ergosterol contained in Polyporus sclerotium is the main active component. In this study, we analyzed the mechanism by which ergosterol inhibits bladder carcinogenesis. Rats were given an N-butyl-N(4-hydroxybutyl) nitrosamine (BHBN) solution ad libitum, and then a promoter [saccharin sodium (SS), DL-tryptophan, or BHBN] was administered together with ergosterol or its metabolite, brassicasterol. The bladders were removed from rats, and the inhibitory effect on carcinogenesis promotion was evaluated by an agglutination assay with concanavalin A (Con A). Although the oral administration of ergosterol inhibited the promotion of bladder carcinogenesis with SS, the intraperitoneal administration of brassicasterol showed a stronger effect. The effect of brassicasterol on carcinogenesis promotion was observed regardless of the type of promoter. Administration of testosterone to castrated rats increased the number of cell aggregates caused by Con A. In contrast, intraperitoneal administration of brassicasterol to castrated rats treated with testosterone significantly decreased the number of cell aggregates, confirming the inhibition of bladder carcinogenesis promotion. The inhibitory effect of ergosterol on bladder carcinogenesis is due to brassicasterol, a metabolite of ergosterol. The action of brassicasterol via androgen signaling may play a role in the inhibitory effect on bladder carcinogenesis promotion. Keywords Ergosterol · Brassicasterol · Bladder carcinogenesis · Androgen signal
Introduction
Yasuharu Yazawa and Nobutomo Ikarashi have contributed equally to this paper.
Bladder cancer is one of the most common urological tumors. It mainly affects men at a rate of approximately ten times that in women [1]. Approximately 70% of bladder cancers are nonmuscle-invasive and are commonly treated by transurethral resection (TUR). The prognosis after TUR
* Nobutomo Ikarashi [email protected]
3
Department of Clinical Pharmacokinetics, Hoshi University, Tokyo, Japan
* Kiyoshi Sugiyama [email protected]
4
Institute of Traditional Chinese Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
5
Department of Functional Molecular Kinetics, Hoshi University, 2‑4‑41 Ebara, Shinagawa‑ku, Tokyo 142‑8501, Japan
1
Department of Clinical Pharmaceutics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
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