Verapamil augments carmustine- and irradiation-induced senescence in glioma cells by reducing intracellular reactive oxygen species and calcium ion levels
- Authors
- Ham, Seok Won; Jeon, Hee-Young; Kim, Hyunggee
- Issue Date
- 1-5월-2017
- Publisher
- SAGE PUBLICATIONS LTD
- Keywords
- Glioma; senescence; verapamil; carmustine; irradiation
- Citation
- TUMOR BIOLOGY, v.39, no.5
- Indexed
- SCIE
SCOPUS
- Journal Title
- TUMOR BIOLOGY
- Volume
- 39
- Number
- 5
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/83498
- DOI
- 10.1177/1010428317692244
- ISSN
- 1010-4283
- Abstract
- Resistance to conventional therapies and frequent recurrence are the major obstacles to the treatment of high-grade gliomas, including glioblastoma. Thus, the development of new therapeutic strategies to overcome these obstacles is necessary to improve the treatment outcomes. In this study, we found that verapamil, a pan-adenosine triphosphate-binding cassette transporter and L-type voltage-dependent calcium channel inhibitor, sensitized U87MG glioma cells to carmustine- and irradiation-induced senescence. Furthermore, our results indicated that verapamil treatment, in combination with carmustine and irradiation, rendered U87MG glioma cells and several patient-derived glioma stem cells more sensitive to therapy-induced senescence than individual or dual-combination treatments. When investigating the underlying mechanism, we found that verapamil treatment markedly decreased intracellular reactive oxygen species and calcium ion levels. Reactive oxygen species reduction with N-acetylcysteine, a reactive oxygen species scavenger, rendered U87MG glioma cells more sensitive to carmustine and irradiation whereas the protein kinase C agonist, phorbol 12-myristate 13-acetate, mitigated the effects of carmustine and irradiation. Taken together, our results indicate that verapamil may be a potent therapeutic sensitizer for increasing the effectiveness of glioblastoma treatment.
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Collections - Graduate School > Department of Biotechnology > 1. Journal Articles
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