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

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.

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

“…The mRNA expression level of cyclin D1 in bladder epithelial cells was significantly higher in the carcinogenesis group than in the control group. This result was consistent with previous reports using bladder cancer model rats [9]. In contrast, in rats treated with brassicasterol, the expression level of cyclin D1 was significantly decreased compared with that in the carcinogenesis group, which was almost the same as that in the control group.…”

“…The results of this study clarified that brassicasterol suppresses bladder carcinogenesis by acting on cell cycle-related signaling, inflammation-related signaling, and androgen signaling via multiple mechanisms. These effects were similar to those of oral ergosterol administration to bladder cancer model rats [9]. Therefore, it is highly possible that the inhibitory effect of Choreito treatment on bladder carcinogenesis is due to the brassicasterol, which is a metabolite of ergosterol contained in Polyporus Sclerotium.…”

“…We have previously examined Kampo medicines aiming to find new strategies for the prevention of superficial bladder cancer. It was found that (i) Choreito used to treat abnormal urination strongly suppresses the promotion of bladder carcinogenesis [6]; (ii) Polyporus Sclerotium, a crude drug contained in Choreito, has an inhibitory effect on bladder carcinogenesis [7]; (iii) ergosterol contained in Polyporus Sclerotium is the main active ingredient [8]; and (iv) ergosterol acts on various aspects, such as cell cycle‐related signaling, inflammation‐related signaling, and androgen signaling [9]. In addition, research has clarified that the ergosterol metabolite brassicasterol suppresses bladder carcinogenesis, and the results of experiments using castrated rats suggest that this action may be due to its inhibitory effect on androgen signaling [10].…”

Potential Beneficial Effects and Pharmacological Properties of Ergosterol, a Common Bioactive Compound in Edible Mushrooms

“…Ergosterol also alleviates the symptoms of LPS-induced acute lung injury in mice by downregulating COX-2 expression [ 58 ]. Another study also reported that ergosterol suppresses mRNA expression of COX-2 in rat bladders [ 59 ].…”

Pharmacological Studies on Traditional Plant-Based Remedies

“…Ikarashi et al, starting from previously data that suggest an inhibitory effect byergosterol on bladder carcinogenesis, elucidated its molecular mechanism using a rat model of N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced bladder cancer. They also analyzed various aspects of the cell cycle, inflammation-related signaling, and androgen signaling, suggesting that ergosterol inhibits bladder carcinogenesis [ 10 ]. Georgieva et al demonstrated that hemocyanins isolated from H. aspersa , H. lucorum, and R. venosa , as well as the mucus from H. aspersa exert an antitumor activity in vitro against colorectal carcinoma cell line HT-29, reducing cell viability with a mechanism that includes the induction of apoptosis [ 11 ].…”