Ganoboninketal C from Ganoderma boninense improves the efficacy of CDDP-based chemotherapy through inhibiting translesion DNA synthesis

作     者：Xiaolu Ma Fei Yang Ke Ma Hongyan Shen Junjie Han Kai Wang Yeran Yang Jiawei Zhu Ruiyuan An Qilin Wang Tie-Shan Tang Bo Zhou Hongwei Liu Caixia Guo Xiaolu Ma;Fei Yang;Ke Ma;Hongyan Shen;Junjie Han;Kai Wang;Yeran Yang;Jiawei Zhu;Ruiyuan An;Qilin Wang;Tie-Shan Tang;Bo Zhou;Hongwei Liu;Caixia Guo

作者机构：College of Biomedical EngineeringTaiyuan University of TechnologyTaiyuan 030024China CAS Key Laboratory of Genomics and Precision MedicineBeijing Institute of Genomics/China National Center for BioinformationUniversity of Chinese Academy of SciencesChinese Academy of SciencesBeijing 100101China State Key Laboratory of Membrane BiologyInstitute of ZoologyUniversity of Chinese Academy of SciencesChinese Academy of SciencesBeijing 100101China Institute of MicrobiologyUniversity of Chinese Academy of SciencesChinese Academy of SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative MedicineBeijing 100101China University of Chinese Academy of SciencesChinese Academy of SciencesBeijing 100101China 

出 版 物：《Food Science and Human Wellness》 (食品科学与人类健康（英文）)

年 卷 期：2024年第13卷第5期

页      面：2982-2992页

核心收录：

学科分类：1008[医学-中药学(可授医学、理学学位)] 1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100602[医学-中西医结合临床] 10[医学] 

基　　金：supported by National Key Research and Development Program of China(2018YFA0108500) NSFC82341006,81673334,31970740,31801144,31800684 and 31701227 Natural Science Foundation of Beijing(IS23071) Postdoctoral Research Foundation of China(2021M703206) Natural Science Foundation of Shanxi Province(202203021211155) the State Key Laboratory of Membrane Biology 

主　　题：Ganoderma boninense Ganoboninketal C Cisplatin chemotherapy Translesion DNA synthesis 

摘      要：Translesion DNA synthesis(TLS)can bypass DNA lesions caused by chemotherapeutic drugs,which usually result in drug *** its key role in mutagenesis and cell survival after DNA damage,inhibition of the TLS pathway has emerged as a potential target for improving the efficacy of DNA-damaging agents such as cisplatin(CDDP),a widely used anticancer ***,few suitable natural TLS inhibitors have been ***,we found that a triterpenoid compound Ganoboninketal C(26-3)from Ganoderma boninense,a traditional Chinese medicine,can impair CDDP-induced TLS polymerase eta(Polη)focus formation,PCNA monoubiquitination as well as ***,26-3 can significantly sensitize tumor cells to CDDP killing and reduce the proportion of cancer stem cells in AGS and promote apoptosis after CDDP ***,26-3 can also sensitize tumor cells to Gefitinib ***,through RNA-seq analysis,we found that 26-3 could abrogate the CDDP-induced upregulation of Polηand PIDD(p53-induced protein with a death domain),2 known factors promoting TLS ***,we found that activating transcription factor 3 is a potential novel TLS *** together,we have identified a natural TLS inhibitor 26-3,which can be potentially used as an adjuvant to improve clinical efficacy.