Skip to main content

Advertisement

SpringerLink
Log in

In vitro effects of topotecan and ionizing radiation on TRAIL/Apo2L-mediated apoptosis in malignant glioma

  • Laboratory Investigation
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Abstract

The survival of patients with malignant gliomas is still unsatisfactory despite multimodality treatment, therefore new therapeutic strategies are required. Tumor necrosis factor apoptosis related ligand (TRAIL/Apo2L), a member of the tumor necrosis factor superfamily, may induce apoptotic cell death in several tumors, but not in normal cells, upon binding with specific receptors. In the present study, the expression and function of TRAIL receptors (TRAIL-R1/DR4 and TRAIL-R2/DR5) has been investigated in five human glioma cell lines (U87, U138, U373, A172, SW1783) in ex vivo tumors and in primary cultures obtained from the tumors. Our data show that gliomas preferentially express TRAIL R2 and that treatment with topotecan, a topoisomerase I inhibitor, significantly up-regulates its expression as detected by flow cytometry and western blotting. Moreover, in most cases, treatment with topotecan resulted in an increased sensitivity to TRAIL-dependent apoptosis, although cyclohexymide had to be added to induce apoptosis. On glioma cell lines, the effects of irradiation on TRAIL receptors were also analysed. In our experimental conditions, irradiation with 2 Gy had a modest additive effect on TRAIL-dependent apoptosis and was not able to modulate TRAIL receptor expression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • WR Shapiro JR Shapiro (1998) ArticleTitleBiology and treatment of malignant glioma Oncology 12 233–240

    Google Scholar 

  • A Ashkenazi RC Pai S Fong S Leung DA Lawrence SA Masters C Blackie L Chang AE McMurtrey A Herbert L DeForge IL Koumenis D Lewis L Harris J Bussiere H Koeppen Z Shahrokh RH Schwall (1999) ArticleTitleSafety and antitumor activity of recombinant soluble Apo2 ligand J Clin Invest 104 155–162 Occurrence Handle1:CAS:528:DyaK1MXkslSmsbw%3D Occurrence Handle10411544

    CAS  PubMed  Google Scholar 

  • H Walczak RE Miller K Ariail B Gliniak TS Griffith M Kubin W Chin J Jones A Woodward T Le C Smith P Smolak RG Goodwin CT Rauch JC Schuh DH Lynch (1999) ArticleTitleTumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo Nature Med 5 157–163

    Google Scholar 

  • A Ashkenazi (2002) ArticleTitleTargeting death and decoy receptors of the tumor necrosis factor superfamily Nat Rev Cancer 2 420–430

    Google Scholar 

  • T Yamanaka K Shiraki K Sugimoto M Ito K Takase M Moriyama T Nakano A Suzuki (2000) ArticleTitleChemotherapeutic agents augment TRAIL-induced apoptosis in human hepatocellular carcinoma cell lines Hepatology 32 482–490

    Google Scholar 

  • M Nagane G Pan JJ Weddle VM Dixit WK Cavenee HJ Su Huang (2000) ArticleTitleIncreased death receptor 5 expression by chemotherapeutic agents in human gliomas causes synergistic cytotoxicity with tumor necrosis factor-related apoptosis-inducing ligand in vitro and in vivo Cancer Res 60 847–853 Occurrence Handle1:CAS:528:DC%2BD3cXhs1Siu7w%3D Occurrence Handle10706092

    CAS  PubMed  Google Scholar 

  • Y Mizutani M Nakao O Ogawa O Yoshida B Bonavida T Miki (2001) ArticleTitleEnhanced sensitivity of bladder cancer cells to tumor necrosis factor related apotosis inducing ligand mediated apoptosis by cisplatin and carboplatin J Urol 165 263–270

    Google Scholar 

  • Y Arizono H Yoshikawa H Nagamuna Y Hamada Y Nakajima K Tasaka (2003) ArticleTitleA mechanism of resistance to TRAIL/Apo 2L-induced apoptosis of newly established glioma cell line and sensitisation to TRAIL by gentoxic agents Br J Cancer 88 298–306 Occurrence Handle10.1038/sj.bjc.6600666 Occurrence Handle1:CAS:528:DC%2BD3sXhsV2rt70%3D Occurrence Handle12610517

    Article  CAS  PubMed  Google Scholar 

  • E Ciusani P Perego N Carenini E Corna F Facchinetti A Boiardi A Salmaggi F Zunino (2002) ArticleTitleFas/CD95-mediated apoptosis in human glioblastoma cells: a target for sensitisation to topoisomerase I inhibitors Biochem Pharmacol 63 881–887

    Google Scholar 

  • MS Sheikh TF Burns Y Huang GS Wu S Amundson KS Brooks AJ Fornace SuffixJr WS el-Deiry (1998) ArticleTitlep53 dependent and independent regulation of the death receptor KILLER/DR5 gene expression in response to genotoxic stress and tumor necrosis factor alfa Cancer Res 58 1593–1598

    Google Scholar 

  • SN Sanghavi MN Needle MD Krailo JR Geyer J Ater MP Mehta (2003) ArticleTitleA phase I study of topotecan as a radiosensitizer for brainstem glioma of childhood: first report of the Children’s Cancer Group-0952 Neuro-oncology 5 8–13

    Google Scholar 

  • B Gong A Almasan (2000) ArticleTitleApo2 ligand/TNF-related apoptosis-inducing ligand and death receptor 5 mediate the apoptotic signaling induced by ionizing radiation in leukemic cells Cancer Res 60 5754–5760

    Google Scholar 

  • HK Rooprai A Merzak P Bullok GJ Pilkington (1997) ArticleTitleEstablishment and characterization of two paediatric brain tumor cell line in vitro Anticancer Res 17 4127–4134

    Google Scholar 

  • S Spiegl-Kreinecker J Buchtroithner L Elbling E Steiner G Wurm A Bodenteich J Fischer M Micksche W Berger (2002) ArticleTitleExpression and functional activity of the ABC-transporter protein P-glycoprotein and multidrug-resistance protein 1 in human brain tumor cells and astrocytes J Neuro-Oncol 57 27–36

    Google Scholar 

  • F Spinozzi E Agea O Bistoni A Travetti G Migliorati R Moraca I Nicoletti C Riccardi FP Paoletti R Vaccaro A Bertotto (1995) ArticleTitleT lymphocytes bearing the gamma delta T cell receptor are susceptible of steroid-induced programmed cell death Scand J Immunol 41 504–508

    Google Scholar 

  • HJ Guchelaar A Vermes I Vermes C Haanen (1997) ArticleTitleApoptosis: Molecular mechanisms and implications for cancer chemotherapy Pharm Word Sci 19 119–125

    Google Scholar 

  • LA Tartaglia DV Goeddel (1992) ArticleTitleTwo TNF receptors Immunol Today 13 151–153 Occurrence Handle10.1016/0167-5699(92)90116-O Occurrence Handle1:CAS:528:DyaK38XltV2nu7k%3D Occurrence Handle1322675

    Article  CAS  PubMed  Google Scholar 

  • S Nagata (1997) ArticleTitleApoptosis by death factors Cell 88 355–365 Occurrence Handle10.1016/S0092-8674(00)81874-7

    Article  Google Scholar 

  • D Lawrence Z Shahrokh S Marsters K Achilles D Shih B Mounho K Hillan K Torpal L DeForge P Schow I Hooley S Sherwood R Pai S Leung L Khan B Gliniak J Bussiere CA Smith SS Strom S Kelley JA Fox D Thomas A Ashkenazi (2001) ArticleTitleDifferential hepatocyte toxicity to recombinant Apo2L/TRAIL versions Nat Med 7 383–385

    Google Scholar 

  • C Hao F Beguinot G Condorelli A Trencia EG Meir ParticleVan VW Yong IF Parney WH Roa KC Petrok (2001) ArticleTitleInduction and intracellular regulation of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) mediated apoptosis in human malignant glioma cells Cancer Res 61 1162–1170

    Google Scholar 

  • TA Röhn B Wagenknecht W Roth U Naumann E Gulbins PH Krammer H Walczak M Weller (2001) ArticleTitleCCNU-dependent potentiation of TRAIL/Apo2L-induced apoptosis in human glioma cells is p53-independent but may involve enhanced cytochrome c release Oncogene 20 4128–4137

    Google Scholar 

  • MJ Knight CD Riffkin AM Muscat DM Ashley CJ Hawkins (2001) ArticleTitleAnalysis of FasL and TRAIL induced apoptosis pathwas in glioma cells Oncogene 20 5789–5798

    Google Scholar 

  • F Schmidt J Rieger J Wischhusen U Naumann M Weller (2001) ArticleTitleGlioma sensitivity to topotecan: the role of p53 and topotecan-induced DNA damage Eur J Pharmacol 412 21–25

    Google Scholar 

  • GS Wu TF Burns ER McDonald SuffixIII W Jiang R Meng ID Kranz G Kao DD Gan JY Zhou R Muschel RS Hamilton NB Spinner S Markovitz G Wu W el-Deiry (1997) ArticleTitleKILLED/DR5 is a DNA damage inducible p-53 regulated death receptor gene Nat Genet 7 141–143

    Google Scholar 

  • AM Chinnaiyan U Prasad S Shancar DA Hamstra M Shanaiah TL Chenevert BD Ross A Rehemtulla (2000) ArticleTitleCombined effect of tumor necrosis factor-related apoptosis-inducing ligand and ionizing radiation in breast cancer therapy Proc Natl Acad Sci 97 1754–1759 Occurrence Handle10.1073/pnas.030545097 Occurrence Handle1:CAS:528:DC%2BD3cXhsFCrt70%3D Occurrence Handle10677530

    Article  CAS  PubMed  Google Scholar 

  • R Di Pietro P Sacchiero R Rana D Gibellini G Visani K Bernis L Zamai (2001) ArticleTitleIonizing radiation sensitizes erythroleukemic cells but not normal erythroblasts to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated cytotoxicity by selective up-regulation of TRAIL-R1 Blood 97 2596–2603

    Google Scholar 

  • MR Kim JL Lee MT Park YJ Chu YJ Jang CM Kang HS Kim CK Cho YS Lee HY Jeong SJ Lee (2001) ArticleTitleIonizing radiation can overcome resistance to TRAIL in TRAIL-resistant cancer cells FEBS Letters 505 179–184

    Google Scholar 

  • C Belka B Schmidt P Marini E Durand J Rudner H Faltin M Bamb K Shulze-Osthoff W Budach (2001) ArticleTitleSensitization of resistant lymphoma cells to irradiation-induced apoptosis by the death ligand TRAIL Oncogene 20 2190–2196

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Investigation, National Neurological Institute “C. Besta”, Via Celoria, 11, Milan, Italy, 20133

    Emilio Ciusani, Danilo Croci & Marco Balzarotti

  2. Department of Radiotherapy, National Neurological Institute “C. Besta”, Italy

    Luisa Fumagalli & Laura Fariselli

  3. Department of Neurooncology, National Neurological Institute “C. Besta”, Milan, Italy

    Maurizio Gelati, Chiara Calatozzolo, Francesca Sciacca, Amerigo Boiardi & Andrea Salmaggi

Authors
  1. Emilio Ciusani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Danilo Croci
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maurizio Gelati
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chiara Calatozzolo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Francesca Sciacca
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Luisa Fumagalli
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Marco Balzarotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Laura Fariselli
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Amerigo Boiardi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Andrea Salmaggi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Emilio Ciusani.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ciusani, E., Croci, D., Gelati, M. et al. In vitro effects of topotecan and ionizing radiation on TRAIL/Apo2L-mediated apoptosis in malignant glioma. J Neurooncol 71, 19–25 (2005). https://doi.org/10.1007/s11060-004-9180-4

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-004-9180-4

Keywords

Search

Navigation