Eukaryotic initiation factor 5B (eIF5B) regulates temozolomide-mediated apoptosis in brain tumor stem cells (BTSCs)

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dc.contributor.authorRoss, Joseph A.
dc.contributor.authorAhn, Bo Young
dc.contributor.authorKing, Jennifer
dc.contributor.authorBressler, Kamiko R.
dc.contributor.authorSenger, Donna L.
dc.contributor.authorThakor, Nehal
dc.date.accessioned2020-11-04T19:49:54Z
dc.date.available2020-11-04T19:49:54Z
dc.date.issued2019
dc.descriptionAccepted author manuscripten_US
dc.description.abstractGlioblastoma multiforme (GBM) is among the deadliest cancers, owing in part to complex inter- and intra-tumor heterogeneity and the presence of a population of stem-like cells called brain tumor stem cells (BTSCs/BTICs). These cancer stem cells survive treatment and confer resistance to the current therapies—namely, radiation and the chemotherapeutic, temozolomide (TMZ). TMZ induces cell death by alkylating DNA, and BTSCs resist this mechanism via a robust DNA damage response. Hence, recent studies aimed to sensitize BTSCs to TMZ using combination therapy, such as inhibition of DNA repair machinery. We have previously demonstrated in established GBM cell lines that eukaryotic initiation factor 5B (eIF5B) promotes the translation of pro-survival and anti-apoptotic proteins. Consequently, silencing eIF5B sensitizes these cells to TRAIL-induced apoptosis. However, established cell lines do not always recapitulate the features of human glioma. Therefore, we investigated this mechanism in patient-derived BTSCs. We show that silencing eIF5B leads to increased TMZ sensitivity in two BTSC lines, BT25 and BT48. Depletion of eIF5B decreases levels of anti-apoptotic proteins in BT48 and sensitizes these cells to TMZ-induced activation of caspase-3, cleavage of PARP, and apoptosis. We suggest that eIF5B represents a rational target to sensitize GBM tumors to the current standard-of-care.en_US
dc.description.peer-reviewYesen_US
dc.identifier.citationRoss, J. A., Ahn, B. Y., King, J., Bressler, K. R., Senger, D. L., & Thakor, N.(2019). Eukaryotic initiation factor 5B (eIF5B) regulates temozolomide-mediated apoptosis in brain tumor stem cells (BTSC)s. Biochemistry and Cell Biology, 98(6), 647-652. https://doi.org/10.1139/bcb-2019-0329en_US
dc.identifier.urihttps://hdl.handle.net/10133/5800
dc.language.isoen_USen_US
dc.publisherCanadian Science Publishingen_US
dc.publisher.departmentDepartment of Chemistry and Biochemistryen_US
dc.publisher.departmentDepartment of Neuroscienceen_US
dc.publisher.facultyArts and Scienceen_US
dc.publisher.institutionUniversity of Lethbridgeen_US
dc.publisher.institutionUniversity of Calgaryen_US
dc.publisher.urlhttps://doi.org/10.1139/bcb-2019-0329en_US
dc.subjectEukaryotic initiation factor 5B (eIF5B)en_US
dc.subjectBrain tumor stem cells (BTSCs)en_US
dc.subjectApoptosisen_US
dc.subjectTemozolomide (TMZ)en_US
dc.subjectGlioblastoma multiforme (GBM)en_US
dc.subject.lcshBrain--Tumors
dc.subject.lcshCell death
dc.subject.lcshCancer--Research
dc.titleEukaryotic initiation factor 5B (eIF5B) regulates temozolomide-mediated apoptosis in brain tumor stem cells (BTSCs)en_US
dc.typeArticleen_US
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