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Survivin Inhibition by Piperine Sensitizes Glioblastoma Cancer Stem Cells and Leads to Better Drug Response
Neerada Meenakshi Warrier1, Ramesh Kumar Krishnan2,3, Vijendra Prabhu1
1Department of Biotechnology, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India.
Abstract:
Glioblastoma multiforme (GBM) cancer stem cells (GSCs) are one of the strongest contributing factors to treatment resistance in GBM. Identification of biomarkers capable of directly affecting these cells within the bulk tumor is a major challenge associated with the development of new targeting strategies. In this study, we focus on understanding the potential of the multifunctional extraordinaire survivin as a biomarker for GSCs. We analyzed the expression profiles of this gene using various publicly available datasets to understand its importance in stemness and other cancer processes. The findings from these studies were further validated using human GSCs isolated from a GBM cell line. In these GSCs, survivin was inhibited using the dietary phytochemical piperine (PIP) and the subsequent effects on stemness, cancer processes and Temozolomide were investigated. In silico analysis identified survivin to be one of the most significant differentially regulated gene in GSCs, in comparison to common stemness markers. Further validation studies on the isolated GSCs showed the importance of survivin in stemness, cancer progression and therapy resistance. Taken together, our study identifies survivin as a more consistent GSC marker and also suggests the possibility of using survivin inhibitors along with standard of care drugs for better therapeutic outcomes.
Insights
Survivin is a promising biomarker for glioblastoma cancer stem cells (GSCs), showing significant differential regulation. Inhibiting survivin with piperine may enhance glioblastoma treatment outcomes.
Area of Science:
- Oncology
- Cancer Stem Cell Biology
- Molecular Biology
Background:
- Glioblastoma cancer stem cells (GSCs) drive treatment resistance in glioblastoma multiforme (GBM).
- Identifying effective biomarkers for GSCs is crucial for developing targeted therapies.
- Survivin's role as a potential GSC biomarker requires further investigation.
Purpose of the Study:
- To evaluate survivin as a consistent biomarker for glioblastoma cancer stem cells (GSCs).
- To investigate the effect of survivin inhibition on GSC stemness and therapeutic resistance.
Main Methods:
- In silico analysis of publicly available gene expression datasets.
- Isolation and culture of human GSCs from a GBM cell line.
- Inhibition of survivin using piperine (PIP) in GSCs.
- Assessment of stemness, cancer progression, and response to Temozolomide.
Main Results:
- In silico analysis identified survivin as a significantly differentially regulated gene in GSCs compared to other stemness markers.
- Survivin plays a critical role in GSC stemness, cancer progression, and resistance to therapy.
- Piperine effectively inhibited survivin in GSCs, impacting stemness and sensitizing cells to Temozolomide.
Conclusions:
- Survivin is a consistent and reliable biomarker for glioblastoma cancer stem cells.
- Targeting survivin with inhibitors like piperine, in combination with standard treatments, could improve therapeutic outcomes for GBM patients.
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