PUBLICATION
The antibiotic clofoctol suppresses glioma stem cell proliferation by activating KLF13
- Authors
- Hu, Y., Zhang, M., Tian, N., Li, D., Wu, F., Hu, P., Wang, Z., Wang, L., Hao, W., Kang, J., Yin, B., Zheng, Z., Jiang, T., Yuan, J., Qiang, B., Han, W., Peng, X.
- ID
- ZDB-PUB-200527-13
- Date
- 2019
- Source
- The Journal of Clinical Investigation 129: 3072-3085 (Journal)
- Registered Authors
- Keywords
- Brain cancer, Drug screens, Drug therapy, Oncology, Therapeutics
- MeSH Terms
-
- Animals
- Antibiotics, Antineoplastic/pharmacology*
- Cell Cycle Proteins/metabolism
- Cell Line, Tumor
- Cell Proliferation/drug effects*
- Cresols/pharmacology
- DNA-Binding Proteins/metabolism
- Glioma/drug therapy*
- Glioma/metabolism
- Glioma/pathology
- Humans
- Kruppel-Like Transcription Factors/metabolism
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Neoplasm Proteins/metabolism
- Neoplastic Stem Cells/metabolism*
- Neoplastic Stem Cells/pathology
- RNA-Binding Proteins/metabolism
- Repressor Proteins/metabolism
- Xenograft Model Antitumor Assays
- Zebrafish
- PubMed
- 31112526 Full text @ Journal of Clin. Invest.
Citation
Hu, Y., Zhang, M., Tian, N., Li, D., Wu, F., Hu, P., Wang, Z., Wang, L., Hao, W., Kang, J., Yin, B., Zheng, Z., Jiang, T., Yuan, J., Qiang, B., Han, W., Peng, X. (2019) The antibiotic clofoctol suppresses glioma stem cell proliferation by activating KLF13. The Journal of Clinical Investigation. 129:3072-3085.
Abstract
Gliomas account for approximately 80% of primary malignant tumors in the central nervous system. Despite aggressive therapy, the prognosis of patients remains extremely poor. Glioma stem cells (GSCs) which considered as the potential target of therapy for their crucial role in therapeutic resistance and tumor recurrence, are believed to be key factors for the disappointing outcome. Here, we took advantage of GSCs as the cell model to perform high-throughput drug screening and the old antibiotic, clofoctol, was identified as the most effective compound, showing reduction of colony-formation and induction of apoptosis of GSCs. Moreover, growth of tumors was inhibited obviously in vivo after clofoctol treatment especially in primary patient-derived xenografts (PDXs) and transgenic xenografts. The anticancer mechanisms demonstrated by analyzing related downstream genes and discovering the targeted binding protein revealed that clofoctol exhibited the inhibition of GSCs by upregulation of Kruppel-like factor 13 (KLF13), a tumor suppressor gene, through clofoctol's targeted binding protein, Upstream of N-ras (UNR). Collectively, these data demonstrated that induction of KLF13 expression suppressed growth of gliomas and provided a potential therapy for gliomas targeting GSCs. Importantly, our results also identified the RNA-binding protein UNR as a drug target.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping