Interferon- β sensitizes human glioblastoma cells to the cyclin-dependent kinase inhibitor, TG02.

Interferon-β sensitizes human glioblastoma cells to the cyclin-dependent kinase inhibitor, TG02. Oncol Lett. 2020 Apr;19(4):2649-2656 Authors: Lohmann B, Rhun EL, Silginer M, Epskamp M, Weller M Abstract Novel treatments for glioblastoma, the most common malignant primary brain tumor, are urgently required. Type I interferons (IFN) are natural cytokines primarily involved in the defense against viral infections, which may also serve a role in the control of cancer, notably in the suppression of the cancer stem cell phenotype. TG02 is a novel orally available cyclin-dependent kinase 9 inhibitor which induces glioma cell apoptosis without profound caspase activation, which is currently explored in early clinical trials in newly diagnosed and recurrent glioblastoma. In the present study, human glioma-initiating cell line models were used to explore whether IFN-β modulates the anti-glioma activity of TG02. The present study employed immunoblotting to assess protein levels, several viability assays and gene silencing strategies to assess gene function. Pre-exposure to IFN-β sensitized human glioma models to a subsequent exposure to TG02. Combination treatment was associated with increased DEVD-amc cleaving caspase activity that was blocked by the anti-apoptotic protein, BCL2. However, BCL2 did not protect from the synergistic effects of IFN and TG02 on glioma cell growth. Furthermore, although IFN strongly induced pro-apoptotic XIAP-as...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research