Survivin Inhibition by Piperine Sensitizes Glioblastoma Cancer Stem Cells and Leads to Better Drug Response
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 stra...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-07-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/14/7604 |
| _version_ | 1797446566965936128 |
|---|---|
| author | Neerada Meenakshi Warrier Ramesh Kumar Krishnan Vijendra Prabhu Raghu Chandrashekhar Hariharapura Prasoon Agarwal Praveen Kumar |
| author_facet | Neerada Meenakshi Warrier Ramesh Kumar Krishnan Vijendra Prabhu Raghu Chandrashekhar Hariharapura Prasoon Agarwal Praveen Kumar |
| author_sort | Neerada Meenakshi Warrier |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T13:43:22Z |
| format | Article |
| id | doaj.art-872fc2beb91c44d793403097e390ac72 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T13:43:22Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-872fc2beb91c44d793403097e390ac722023-11-30T21:04:06ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012314760410.3390/ijms23147604Survivin Inhibition by Piperine Sensitizes Glioblastoma Cancer Stem Cells and Leads to Better Drug ResponseNeerada Meenakshi Warrier0Ramesh Kumar Krishnan1Vijendra Prabhu2Raghu Chandrashekhar Hariharapura3Prasoon Agarwal4Praveen Kumar5Department of Biotechnology, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal 576104, Karnataka, IndiaDepartment of Medicine II, Hematology and Oncology, University Hospital Frankfurt, Goethe University, 60590 Frankfurt, GermanyDepartment of Biotechnology, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal 576104, Karnataka, IndiaDepartment of Pharmaceutical Biotechnology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, IndiaNational Bioinformatics Infrastructure Sweden (NBIS), SciLifeLab, Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, 22362 Lund, SwedenDepartment of Biotechnology, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal 576104, Karnataka, IndiaGlioblastoma 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.https://www.mdpi.com/1422-0067/23/14/7604glioblastoma cancer stem cellstherapeutic targetingsurvivinpiperinetemozolomideintegrative analysis |
| spellingShingle | Neerada Meenakshi Warrier Ramesh Kumar Krishnan Vijendra Prabhu Raghu Chandrashekhar Hariharapura Prasoon Agarwal Praveen Kumar Survivin Inhibition by Piperine Sensitizes Glioblastoma Cancer Stem Cells and Leads to Better Drug Response International Journal of Molecular Sciences glioblastoma cancer stem cells therapeutic targeting survivin piperine temozolomide integrative analysis |
| title | Survivin Inhibition by Piperine Sensitizes Glioblastoma Cancer Stem Cells and Leads to Better Drug Response |
| title_full | Survivin Inhibition by Piperine Sensitizes Glioblastoma Cancer Stem Cells and Leads to Better Drug Response |
| title_fullStr | Survivin Inhibition by Piperine Sensitizes Glioblastoma Cancer Stem Cells and Leads to Better Drug Response |
| title_full_unstemmed | Survivin Inhibition by Piperine Sensitizes Glioblastoma Cancer Stem Cells and Leads to Better Drug Response |
| title_short | Survivin Inhibition by Piperine Sensitizes Glioblastoma Cancer Stem Cells and Leads to Better Drug Response |
| title_sort | survivin inhibition by piperine sensitizes glioblastoma cancer stem cells and leads to better drug response |
| topic | glioblastoma cancer stem cells therapeutic targeting survivin piperine temozolomide integrative analysis |
| url | https://www.mdpi.com/1422-0067/23/14/7604 |
| work_keys_str_mv | AT neeradameenakshiwarrier survivininhibitionbypiperinesensitizesglioblastomacancerstemcellsandleadstobetterdrugresponse AT rameshkumarkrishnan survivininhibitionbypiperinesensitizesglioblastomacancerstemcellsandleadstobetterdrugresponse AT vijendraprabhu survivininhibitionbypiperinesensitizesglioblastomacancerstemcellsandleadstobetterdrugresponse AT raghuchandrashekharhariharapura survivininhibitionbypiperinesensitizesglioblastomacancerstemcellsandleadstobetterdrugresponse AT prasoonagarwal survivininhibitionbypiperinesensitizesglioblastomacancerstemcellsandleadstobetterdrugresponse AT praveenkumar survivininhibitionbypiperinesensitizesglioblastomacancerstemcellsandleadstobetterdrugresponse |