Transcriptional cdk inhibitors cyc065 and thz1 induce apoptosis in glioma stem cells derived from recurrent gbm
| Autor: | Martine L.M. Lamfers, Jochen H M Prehn, Viktorija Juric, Heiko Düssmann, Brona M. Murphy, Markus Rehm |
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| Přispěvatelé: | Neurosurgery |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Adenosine Apoptosis Stem cell marker 0302 clinical medicine AC133 Antigen CD133 Biology (General) CD44 0303 health sciences biology Brain Neoplasms Glioma General Medicine Middle Aged 3. Good health Hyaluronan Receptors 030220 oncology & carcinogenesis Neoplastic Stem Cells CYC065 Stem cell CDK inhibitors medicine.drug Adult Programmed cell death QH301-705.5 recurrent GBM Antineoplastic Agents Article 03 medical and health sciences Cyclin-dependent kinase Cell Line Tumor Temozolomide medicine Humans Cell Proliferation 030304 developmental biology business.industry Cell growth Cell Cycle Checkpoints medicine.disease THZ1 Drug Resistance Neoplasm biology.protein Cancer research glioma stem cells cyclin-dependent kinases Neoplasm Recurrence Local business |
| Zdroj: | Cells, 10(5):1182. Multidisciplinary Digital Publishing Institute (MDPI) Cells Volume 10 Issue 5 Cells, Vol 10, Iss 1182, p 1182 (2021) |
| ISSN: | 2073-4409 |
| Popis: | Glioma stem cells (GSCs) are tumour initiating cells which contribute to treatment resistance, temozolomide (TMZ) chemotherapy and radiotherapy, in glioblastoma (GBM), the most aggressive adult brain tumour. A major contributor to the uncontrolled tumour cell proliferation in GBM is the hyper activation of cyclin-dependent kinases (CDKs). Due to resistance to standard of care, GBMs relapse in almost all patients. Targeting GSCs using transcriptional CDK inhibitors, CYC065 and THZ1 is a potential novel treatment to prevent relapse of the tumour. TCGA-GBM data analysis has shown that the GSC markers, CD133 and CD44 were significantly upregulated in GBM patient tumours compared to non-tumour tissue. CD133 and CD44 stem cell markers were also expressed in gliomaspheres derived from recurrent GBM tumours. Light Sheet Florescence Microscopy (LSFM) further revealed heterogeneous expression of these GSC markers in gliomaspheres. Gliomaspheres from recurrent tumours were highly sensitive to transcriptional CDK inhibitors, CYC065 and THZ1 and underwent apoptosis while being resistant to TMZ. Apoptotic cell death in GSC subpopulations and non-stem tumour cells resulted in sphere disruption. Collectively, our study highlights the potential of these novel CKIs to induce cell death in GSCs from recurrent tumours, warranting further clinical investigation. |
| Databáze: | OpenAIRE |
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