Carrimycin,a first in-class anti-cancer agent,targets selenoprotein H to induce nucleolar oxidative stress and inhibit ribosome biogenesis  

作　　者：LaYow C.Yu Danielle D.Dang Sophie Zhuang Shuran Chen Zhengping Zhuang Jared S.Rosenblum 

机构地区：[1]Neuro-Oncology Branch,National Cancer Institute,National Institutes of Health,Bethesda,MD,20892,United States

出　　处：《Cancer Pathogenesis and Therapy》2023年第2期111-115,共5页癌症发生与治疗（英文）

基　　金：supported in part by the Intramural Program of the NCI and NINDS(National Institutes of Health)and did not receive any specific grant from funding agencies(e.g.,public,commercial,or not-forprofit sectors)outside of the authors'academic institution.

摘　　要：Carrimycin is a synthetic macrolide antibiotic that has been shown to have anti-cancer activity;however,its exact mechanism of action and molecular target were previously unknown.It was recently elucidated that Isovalerylspiramycin I(ISP I),the active component of carrimycin,targets selenoprotein H(SelH),a nucleolar reactive oxygen species-scavenging enzyme in the selenoprotein family.ISP I treatment accelerates SelH degradation,resulting in oxidative stress,disrupted ribosomal biogenesis,and apoptosis in tumor cells.Specifically,ISP I disrupts the association between RNA polymerase I and ribosomal DNA in the nucleolus.This inhibits ribosomal RNA transcription and subsequent ribosomal assembly,which prevents cancer cells from sustaining elevated rates of protein synthesis and cellular proliferation that are necessary for tumor growth and malignancy.In this review,we(1)describe the historical categorization and evolution of anti-cancer agents,including macrolide antibiotics,(2)outline the discovery of SelH as a target of ISP I,and(3)summarize the ways in which carrimycin has been used both clinically and at the bench to date and propose additional potential therapeutic uses.

关 键 词：SELENOPROTEIN Ribosome biogenesis MACROLIDE Cancer Carrimycin 

分 类 号：R730.2[医药卫生—肿瘤]