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Inhibitory effect of ergosterol on bladder carcinogenesis is due to androgen signaling inhibition by brassicasterol, a metabolite of ergosterol.
Journal of Natural Medicines ( IF 3.3 ) Pub Date : 2020-06-01 , DOI: 10.1007/s11418-020-01419-4
Yasuharu Yazawa 1 , Nobutomo Ikarashi 2 , Motohiro Hoshino 3 , Hironori Kikkawa 4 , Fumiyo Sakuma 4 , Kiyoshi Sugiyama 5
Affiliation  

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.

中文翻译:

麦角固醇对膀胱癌发生的抑制作用是由于黄铜固醇(一种麦角固醇的代谢物)对雄激素信号的抑制作用。

我们之前曾透露,传统的Kampo药物Choreito强烈抑制膀胱癌的发生。我们还显示了猪Poly菌核菌,它是Choreito中的粗制药物之一,具有最强的膀胱癌发生抑制作用,并且猪Poly菌核菌中所含的麦角固醇是主要的活性成分。在这项研究中,我们分析了麦角固醇抑制膀胱癌变的机制。随意给予大鼠N-丁基-N-(4-羟丁基)亚硝胺(BHBN)溶液,然后将启动子[糖精钠(SS),DL-色氨酸或BHBN]与麦角固醇或其代谢物一起给药,芸苔甾醇。从大鼠取出膀胱,并通过伴刀豆球蛋白A(Con A)的凝集测定评价对促进癌发生的抑制作用。尽管口服麦角固醇抑制了SS促进膀胱癌的发生,但腹膜内施用油菜固醇显示出更强的作用。无论启动子的类型如何,都观察到了芸苔甾醇对促进癌变的作用。向cast割的大鼠施用睾丸激素会增加由Con A引起的细胞聚集体的数量。相反,向经睾丸酮处理的cast割的大鼠腹膜内给予芸苔甾醇会明显减少细胞聚集体的数量,从而证实了对膀胱癌发生促进的抑制作用。麦角固醇对膀胱癌的抑制作用归因于油菜固醇(麦角固醇的代谢产物)。芸苔甾醇通过雄激素信号传导的作用可能在对膀胱癌发生促进的抑制作用中起作用。麦角固醇对膀胱癌的抑制作用归因于油菜固醇(麦角固醇的代谢产物)。芸苔甾醇通过雄激素信号传导的作用可能在对膀胱癌发生促进的抑制作用中起作用。麦角固醇对膀胱癌的抑制作用归因于油菜固醇(麦角固醇的代谢产物)。芸苔甾醇通过雄激素信号传导的作用可能在对膀胱癌发生促进的抑制作用中起作用。
更新日期:2020-06-01
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