We are analyzing https://link.springer.com/article/10.1007/s10495-013-0935-2.

Title:
Modulation of Mcl-1 sensitizes glioblastoma to TRAIL-induced apoptosis | Apoptosis
Description:
Glioblastoma (GBM) is the most aggressive form of primary brain tumour, with dismal patient outcome. Treatment failure is associated with intrinsic or acquired apoptosis resistance and the presence of a highly tumourigenic subpopulation of cancer cells called GBM stem cells. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) has emerged as a promising novel therapy for some treatment-resistant tumours but unfortunately GBM can be completely resistant to TRAIL monotherapy. In this study, we identified Mcl-1, an anti-apoptotic Bcl-2 family member, as a critical player involved in determining the sensitivity of GBM to TRAIL-induced apoptosis. Effective targeting of Mcl-1 in TRAIL resistant GBM cells, either by gene silencing technology or by treatment with R-roscovitine, a cyclin-dependent kinase inhibitor that targets Mcl-1, was demonstrated to augment sensitivity to TRAIL, both within GBM cells grown as monolayers and in a 3D tumour model. Finally, we highlight that two separate pathways are activated during the apoptotic death of GBM cells treated with a combination of TRAIL and R-roscovitine, one which leads to caspase-8 and caspase-3 activation and a second pathway, involving a Mcl-1:Noxa axis. In conclusion, our study demonstrates that R-roscovitine in combination with TRAIL presents a promising novel strategy to trigger cell death pathways in glioblastoma.
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Keywords {🔍}

cells, trail, mcl, rroscovitine, cell, treatment, apoptosis, pubmed, article, google, scholar, cas, expression, gbm, fig, levels, noxa, death, treated, caspase, cancer, trailinduced, glioblastoma, tumour, activation, apoptotic, data, neurospheres, lines, resistance, bcl, ngml, observed, downregulation, control, protein, glioma, stem, percentage, proteins, knockdown, shrna, combination, expressed, panel, significant, central, study, targeting, signalling,

Topics {✒️}

tumour-necrosis factor superfamily serum-free neurosphere-forming medium quantitative real-time pcr r-roscovitine-induced inhibitory effects r-roscovitine + trail induces apoptosis death receptors dr4/trail-r1 cyclin-dependent kinase inhibitor r-roscovitine + trail-induced apoptosis dana-farber cancer institute egf/erbb1 signaling pathway article download pdf pe-conjugated secondary antibodies cellular flice-inhibitory protein vorinostat-induced apoptosis depends fitc-conjugated secondary antibodies r-roscovitine + trail significantly decreased override pro-inflammatory signalling stem cell-related “ water-insoluble mtt formazan inducing cell death glioblastoma-derived stem cells apoptosis-inducing effects gfp-expressing scramble control epidermal growth factor r-roscovitine-induced sensitisation establish trail-induced killing r-roscovitine-induced apoptosis r-roscovitine-mediated cflip downregulation establish trail-induced apoptosis annexin v-fitc conjugate trail-induced apoptosis mediated tumor cell repopulation related subjects r-roscovitine + trail treatment strategy trail-induced apoptotic signalling fibroblast growth factor trail-induced apoptosis—results bcl-2 family members anti-apoptotic protein mcl-1 survival-related genes trail-mediated mitochondrial apoptosis histone deacetylase inhibitors c-myc-mediated downregulation subsequent combined r-roscovitine human brain tumors full access death receptor signals western blot analysis induces cell death stem cell markers

Questions {❓}

Kuijlen JM et al (2010) Review: on TRAIL for malignant glioma therapy?

Schema {🗺️}

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         description:Glioblastoma (GBM) is the most aggressive form of primary brain tumour, with dismal patient outcome. Treatment failure is associated with intrinsic or acquired apoptosis resistance and the presence of a highly tumourigenic subpopulation of cancer cells called GBM stem cells. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) has emerged as a promising novel therapy for some treatment-resistant tumours but unfortunately GBM can be completely resistant to TRAIL monotherapy. In this study, we identified Mcl-1, an anti-apoptotic Bcl-2 family member, as a critical player involved in determining the sensitivity of GBM to TRAIL-induced apoptosis. Effective targeting of Mcl-1 in TRAIL resistant GBM cells, either by gene silencing technology or by treatment with R-roscovitine, a cyclin-dependent kinase inhibitor that targets Mcl-1, was demonstrated to augment sensitivity to TRAIL, both within GBM cells grown as monolayers and in a 3D tumour model. Finally, we highlight that two separate pathways are activated during the apoptotic death of GBM cells treated with a combination of TRAIL and R-roscovitine, one which leads to caspase-8 and caspase-3 activation and a second pathway, involving a Mcl-1:Noxa axis. In conclusion, our study demonstrates that R-roscovitine in combination with TRAIL presents a promising novel strategy to trigger cell death pathways in glioblastoma.
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            Cancer Research
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      headline:Modulation of Mcl-1 sensitizes glioblastoma to TRAIL-induced apoptosis
      description:Glioblastoma (GBM) is the most aggressive form of primary brain tumour, with dismal patient outcome. Treatment failure is associated with intrinsic or acquired apoptosis resistance and the presence of a highly tumourigenic subpopulation of cancer cells called GBM stem cells. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) has emerged as a promising novel therapy for some treatment-resistant tumours but unfortunately GBM can be completely resistant to TRAIL monotherapy. In this study, we identified Mcl-1, an anti-apoptotic Bcl-2 family member, as a critical player involved in determining the sensitivity of GBM to TRAIL-induced apoptosis. Effective targeting of Mcl-1 in TRAIL resistant GBM cells, either by gene silencing technology or by treatment with R-roscovitine, a cyclin-dependent kinase inhibitor that targets Mcl-1, was demonstrated to augment sensitivity to TRAIL, both within GBM cells grown as monolayers and in a 3D tumour model. Finally, we highlight that two separate pathways are activated during the apoptotic death of GBM cells treated with a combination of TRAIL and R-roscovitine, one which leads to caspase-8 and caspase-3 activation and a second pathway, involving a Mcl-1:Noxa axis. In conclusion, our study demonstrates that R-roscovitine in combination with TRAIL presents a promising novel strategy to trigger cell death pathways in glioblastoma.
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      name:Centre for Systems Medicine, Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland
      name:Centre for Systems Medicine, Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland
      name:Centre for Systems Medicine, Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland
      name:Centre for Systems Medicine, Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland
      name:Experimental Neurosurgery, Centre for Neurology and Neurosurgery, Johann Wolfgang Goethe University Hospital, Frankfurt, Germany
      name:Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, USA
      name:Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA
      name:Centre for Systems Medicine, Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland
      name:Centre for Systems Medicine, Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland

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