文献类型：期刊文献

英文题名：Discovery of a Novel Bloom's Syndrome Protein (BLM) Inhibitor Suppressing Growth and Metastasis of Prostate Cancer

作者：Ma, Xiao-Yan Xu, Hou-Qiang Zhao, Jia-Fu Ruan, Yong Chen, Bin

第一作者：马小彦;Ma, Xiao-Yan

通信作者：Xu, HQ[1];Xu, HQ[2]

机构：[1]Guizhou Univ, Coll Life Sci, Minist Educ, Key Lab Anim Genet Breeding & Reprod Plateau Mount, Guiyang 550025, Peoples R China;[2]Guizhou Inst Technol, Coll Food & Pharmaceut Engn, Guiyang 550003, Peoples R China;[3]Guizhou Univ, Coll Anim Sci, Guiyang 550025, Peoples R China

第一机构：Guizhou Univ, Coll Life Sci, Minist Educ, Key Lab Anim Genet Breeding & Reprod Plateau Mount, Guiyang 550025, Peoples R China

通信机构：corresponding author), Guizhou Univ, Coll Life Sci, Minist Educ, Key Lab Anim Genet Breeding & Reprod Plateau Mount, Guiyang 550025, Peoples R China;corresponding author), Guizhou Univ, Coll Anim Sci, Guiyang 550025, Peoples R China.

年份：2022

卷号：23

期号：23

外文期刊名：INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

收录：;Scopus(收录号：2-s2.0-85143765155);WOS:【SCI-EXPANDED(收录号:WOS:000896263100001)】；

基金：This research was funded by the National Natural Science Foundation of China, chaired by Hou-qiang Xu, with grant number 31860242. This research was also funded by Guizhou Province Science and Technology Plan Project, chaired by Xiao-yan Ma, with grant number [2019]1136.

语种：英文

外文关键词：BLM; AO; 854; prostate cancer; cell proliferation; cell apoptosis

摘要：Prostate cancer (PCa) is a common cancer and a major cause of cancer-related death worldwide in men, necessitating novel targets for cancer therapy. High expression of Bloom's syndrome protein (BLM) helicase is associated with the occurrence and development of PCa. Therefore, the identification and development of new BLM inhibitors may be a new direction for the treatment of PCa. Here, we identified a novel inhibitor by molecular docking and put it to systematic evaluation via various experiments, AO/854, which acted as a competitive inhibitor that blocked the BLM-DNA interaction. Cellular evaluation indicated that AO/854-suppressed tumor growth and metastasis in PC3 cells by enhancing DNA damage, phosphorylating Chk1/Chk2, and altering the p53 signaling pathway. Collectively, the study highlights the potential of BLM as a therapeutic target in PCa and reveals a distinct mechanism by which AO/854 competitively inhibits the function of BLM.