Casticin Attenuates Stemness in Cervical Cancer Stem-Like Cells by Regulating Activity and Expression of DNMT1  

作　　者：WANG Xue-li CAO Xiao-zheng WANG Dao-yuan QIU Ye-bei DENG Kai-yu CAO Jian-guo LIN Shao-qiang XU Yong REN Kai-qun 

机构地区：[1]Medical College,Hunan University of Medicine,Huaihua,Hunan Province(418000),China [2]Clinical Department of Guangdong Metabolic Disease Research Centre of Integrated Chinese and Western Medicine,the First Affiliated Hospital of Guangdong Pharmaceutical University,Guangzhou(510062),China [3]Institute of Chemical Biology,Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences,Guangzhou(510530),China [4]The Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province,Medical College,Hunan Normal University,Changsha(410013),China [5]The Key Laboratory of Study and Discover of Small Targeted Molecules of Hunan Province,Medical College,Hunan Normal University,Changsha(410013),China

出　　处：《Chinese Journal of Integrative Medicine》2023年第3期224-232,共9页中国结合医学杂志（英文版）

基　　金：Supported by the National Natural Science Foundation of China(No.82074075);Scientific Research Fund of Hunan Provincial Education Department(No.20C1340);the Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province,Hunan Normal University(No.2017TP1020);the Huxiang High-Level Talent Innovation Team(No.2018RS3072)。

摘　　要：Objective:To explore whether casticin(CAS)suppresses stemness in cancer stem-like cells(CSLCs)obtained from human cervical cancer(CCSLCs)and the underlying mechanism.Methods:Spheres from He La and Ca Ski cells were used as CCSLCs.DNA methyltransferase 1(DNMT1)activity and m RNA levels,self-renewal capability(Nanog and Sox2),and cancer stem cell markers(CD133 and CD44)were detected by a colorimetric DNMT activity/inhibition assay kit,quantitative real-time reverse transcription-polymerase chain reaction,sphere and colony formation assays,and immunoblot,respectively.Knockdown and overexpression of DNMT1 by transfection with sh RNA and c DNA,respectively,were performed to explore the mechanism for action of CAS(0,10,30,and 100 nmol/L).Results:DNMT1 activity was increased in CCSLCs compared with He La and Ca Ski cells(P<0.05).In addition,He La-derived CCSLCs transfected with DNMT1 sh RNA showed reduced sphere and colony formation abilities,and lower CD133,CD44,Nanog and Sox2 protein expressions(P<0.05).Conversely,overexpression of DNMT1 in He La cells exhibited the oppositive effects.Furthermore,CAS significantly reduced DNMT1 activity and transcription levels as well as stemness in He La-derived CCSLCs(P<0.05).Interestingly,DNMT1 knockdown enhanced the inhibitory effect of CAS on stemness.As expected,DNMT1 overexpression reversed the inhibitory effect of CAS on stemness in He La cells.Conclusion:CAS effectively inhibits stemness in CCSLCs through suppression of DNMT1 activation,suggesting that CAS acts as a promising preventive and therapeutic candidate in cervical cancer.

关 键 词：cervical cancer cancer stem cell CASTICIN DNA methyltransferase 1 therapeutic action 

分 类 号：R737.33[医药卫生—肿瘤]