The antibiotic clofoctol suppresses glioma stem cell proliferation by activating KLF13

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), considered a potential target of therapy for their crucial role in therapeutic resistance and tumor recurrence, are believed to be key factors in 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 obviously inhibited in vivo after clofoctol treatment especially in primary patient-derived xenografts and transgenic xenografts. The anticancer mechanisms demonstrated by analysis of related downstream genes and discovery of the targeted binding protein revealed that clofoctol exhibited the inhibition of GSCs by upregulation of Krüppel-like factor 13 (KLF13), a tumor suppressor gene, through clofoctol’s targeted binding protein, Upstream of N-ras (UNR). Collectively, these data demonstrate that induction of KLF13 expression suppressed growth of gliomas and provide a potential therapy for gliomas targeting GSCs. Importantly, our results also identify the RNA-binding protein UNR as a drug target.
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research

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Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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Source: Cellular Oncology - Category: Cancer & Oncology Source Type: research
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Source: Journal of Oncology - Category: Cancer & Oncology Tags: J Oncol Source Type: research
Glioblastoma (GBM) cells with stem cell-like properties are called glioma stem cells (GSCs). GSCs display highly treatment resistance and are responsible for tumor recurrence. Napabucasin (BBI608), a novel sma...
Source: Journal of Experimental and Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Research Source Type: research
a Masashi Okada Glioblastoma is a primary brain tumor associated with a poor prognosis due to its high chemoresistance capacity. Cancer stem cells (CSCs) are one of the mechanisms of chemoresistance. Although therapy targeting CSCs is promising, strategies targeting CSCs remain unsuccessful. Abnormal activation of epidermal growth factor receptors (EGFRs) due to amplification, mutation, or both of the EGFR gene is common in glioblastomas. However, glioblastomas are resistant to EGFR tyrosine kinase inhibitors (EGFR-TKIs), and overcoming resistance is essential. Brexpiprazole is a new, safe serotonin-dopamine activity...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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Source: Cell Stem Cell - Category: Stem Cells Authors: Tags: Cell Stem Cell Source Type: research
Abstract Cancer Stem Cells (CSCs) are the subpopulation of cells present in the tumors with capabilities of self-renewal, differentiation, and tumorigenicity when transplanted into an animal host. Therefore, the research work on the CSC has provided a promising approach for the improvement of cancer therapies in the future. The CSCs have a close connection with the cytokines related with the T helper 17 (Th17) cell and other factors present in the tumor microenvironment, and these play a pivotal role in tumor progression and metastasis. The properties of CSCs are well defined in various type of tumor which is main...
Source: Immunology Letters - Category: Allergy & Immunology Authors: Tags: Immunol Lett Source Type: research
Analytical ChemistryDOI: 10.1021/acs.analchem.8b05941
Source: Analytical Chemistry - Category: Chemistry Authors: Source Type: research
Abstract Cancer stem cells (CSC) are highly associated with poor prognosis in cancer patients. Our previous studies report that isorhapontigenin (ISO) down-regulates SOX2-mediated cyclin D1 induction and stem-like cell properties in glioma stem-like cells. The present study revealed that ISO could inhibit stem cell-like phenotypes and invasivity of human bladder cancer (BC) by specific attenuation of expression of CD44 but not SOX-2, at both the protein transcription and degradation levels. On one hand, ISO inhibited cd44 mRNA expression through decreases in Sp1 direct binding to its promoter region-binding site, ...
Source: Cellular and Molecular Life Sciences : CMLS - Category: Cytology Authors: Tags: Cell Mol Life Sci Source Type: research
Source: Journal of Biomedical Nanotechnology - Category: Nanotechnology Authors: Tags: Articles Source Type: research
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