Work

Discovery of a Novel Bloom’s Syndrome Protein (BLM) Inhibitor Suppressing Growth and Metastasis of Prostate Cancer

Year: 2022

Type: article

Abstract: 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.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms232314798

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

Institutions: Guizhou University, Guizhou Institute of Technology

Language: English

Topic: Prostate Cancer Treatment and Research

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,408