The ER stress inducer DMC enhances TRAIL-induced apoptosis in glioblastoma

SpringerPlus
Ingrid A M van RoosmalenW J Quax

Abstract

Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumour in humans and is highly resistant to current treatment modalities. We have explored the combined treatment of the endoplasmic reticulum (ER) stress-inducing agent 2,5-dimethyl-celecoxib (DMC) and TNF-related apoptosis-inducing ligand (TRAIL WT) or the DR5-specific TRAIL D269H/E195R variant as a potential new strategy to eradicate GBM cells using TRAIL-resistant and -sensitive GBM cells. GBM cell lines were investigated for their sensitivity to TRAIL, DMC and combination of both agents. Cell viability was measured by MTS assay and apoptosis was assessed by Annexin V/PI and acridine orange staining. Caspase activation and protein expression levels were analysed with Western blotting. Death Receptor (DR) cell surface expression levels were quantified by flow cytometry. DR5 expression was increased in U87 cells by ectopic expression using a retroviral plasmid and survivin expression was silenced using specific siRNAs. We demonstrate that A172 expresses mainly DR5 on the cell surface and that these cells show increased sensitivity for the DR5-specific rhTRAIL D269H/E195R variant. In contrast, U87 cells show low DR cell surface levels and is insensitive via b...Continue Reading

References

May 31, 1996·The Journal of Biological Chemistry·R M PittiA Ashkenazi
Jul 20, 1999·The Journal of Clinical Investigation·A AshkenaziR H Schwall
Dec 28, 1999·Annual Review of Cell and Developmental Biology·I BudihardjoX Wang
Apr 3, 2001·Nature Medicine·D LawrenceA Ashkenazi
Aug 16, 2001·Trends in Biochemical Sciences·A S Lee
Apr 12, 2002·Oncogene·Simone FuldaKlaus-Michael Debatin
May 5, 2004·The Journal of Cell Biology·Junichi HitomiMasaya Tohyama
Sep 30, 2004·Journal of the American College of Surgeons·Ladislav MicaMarius Keel
Mar 11, 2005·The New England Journal of Medicine·Roger StuppUNKNOWN National Cancer Institute of Canada Clinical Trials Group
Jul 1, 2005·The Journal of Biological Chemistry·Ken-Ichiro TanakaTohru Mizushima
Dec 24, 2005·Apoptosis : an International Journal on Programmed Cell Death·R KimS Murakami
Jan 7, 2006·Cell Death and Differentiation·J Wu, R J Kaufman
Jan 7, 2006·Cell Death and Differentiation·M Boyce, J Yuan
Feb 14, 2006·Current Molecular Medicine·Jianze Li, Amy S Lee
May 30, 2006·Proceedings of the National Academy of Sciences of the United States of America·Almer M van der SlootWim J Quax
Jan 16, 2007·Neoplasia : an International Journal for Oncology Research·Mingjia TanYi Sun
Aug 19, 2007·Journal of Medicinal Chemistry·Marie M AhlströmKristina Luthman
Aug 31, 2011·Apoptosis : an International Journal on Programmed Cell Death·Ling QiChunhai Hao
Nov 11, 2011·Apoptosis : an International Journal on Programmed Cell Death·Rosa Martín-PérezAbelardo López-Rivas
Mar 6, 2012·Pharmacology & Therapeutics·Adrienne M GormanAfshin Samali
Jul 6, 2012·Expert Opinion on Therapeutic Targets·Markus David Siegelin

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Citations

Oct 27, 2016·Journal of Cellular and Molecular Medicine·Bo ZhangNengming Lin
Jun 24, 2016·Medical Science Monitor : International Medical Journal of Experimental and Clinical Research·Yiye ShaoLixia Zhang
Mar 3, 2018·International Journal of Molecular Sciences·Olivier Micheau
Mar 25, 2017·Molecular and Cellular Biochemistry·Ji-Wei LiuJing Zheng
Apr 4, 2021·International Journal of Molecular Sciences·Jiaqi ZhuJürgen Eberle
Jan 1, 2014·SpringerPlus·Ingrid Am van RoosmalenWim J Quax

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Methods Mentioned

BETA
surgical resection
flow cytometry
flow
Fluorescence
FACS
PCR
activated cell sorter
Transfection

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