Discovery of a Novel Bloom's Syndrome Protein (BLM) Inhibitor Suppressing Growth and Metastasis of Prostate Cancer.
Xiao-Yan MaHou-Qiang XuJia-Fu ZhaoYong RuanBin ChenPublished in: International journal of molecular sciences (2022)
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.
Keyphrases
- prostate cancer
- molecular docking
- signaling pathway
- dna damage
- cancer therapy
- radical prostatectomy
- binding protein
- poor prognosis
- small molecule
- risk assessment
- oxidative stress
- case report
- protein protein
- drug delivery
- high throughput
- pi k akt
- dna damage response
- single molecule
- squamous cell carcinoma
- endoplasmic reticulum stress
- human health
- climate change
- circulating tumor cells
- squamous cell