Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Short Report
  • Published:

Sensitization of resistant lymphoma cells to irradiation-induced apoptosis by the death ligand TRAIL

Oncogene volume 20, pages 2190–2196 (2001)Cite this article

Abstract

A combination of antitumor approaches acting on different death pathways seems ideal for increasing therapeutic responses, especially when defined resistance mechanisms interfere with individual cellular processes. Apoptosis pathways triggered by ionizing radiation (XRT) and the death ligand TRAIL were analysed in Jurkat lymphoma cells. Both induced the activation of caspase-8, caspase-3, BID and mitochondrial potential loss. TRAIL induced apoptosis required caspase-8, whereas it was not essential for radiation induced apoptosis. The inhibition of mitochondrial damage by Bcl-2 abrogated XRT induced apoptosis and caspase activation, but only marginally attenuated TRAIL induced cell death. The combined treatment with TRAIL and XRT exerted additive apoptotic effects in control cells, whereas highly synergistic effects occurred in cells overexpressing Bcl-2. In addition, a strong effect of TRAIL on radiation induced clonogenic cell death was found. In conclusion, TRAIL seems to be of high potential value for a combination with ionizing radiation in tumor therapy.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  • Aldridge DR, Arends MJ, Radford IR . 1995 Br. J. Cancer 71: 571–577

  • Ashkenazi A, Pai RC, Fong S, Leung S, Lawrence DA, Marsters SA, Blackie C, Chang L, McMurtrey AE, Hebert A, DeForge L, Koumenis IL, Lewis D, Harris L, Bussiere J, Koeppen H, Shahrokh Z, Schwall RH . 1999 J. Clin. Invest. 104: 155–162

  • Bargou RC, Daniel PT, Mapara MY, Bommert K, Wagener C, Kallinich B, Royer HD, Dorken B . 1995 Int. J. Cancer 60: 854–859

  • Belka C, Rudner J, Wesselborg S, Stepczynska A, Marini P, Lepple-Wienhues A, Faltin H, Bamberg M, Budach W, Schulze-Osthoff K . 2000 Oncogene 19: 1181–1190

  • Chinnaiyan AM, O'Rourke K, Tewari M, Dixit VM . 1995 Cell 81: 505–512

  • Gibson SB, Oyer R, Spalding AC, Anderson SM, Johnson GL . 2000 Mol. Cell. Biol. 20: 205–212

  • Gong B, Almasan A . 2000 Cancer Res. 60: 5754–5760

  • Greco WR, Bravo G, Parsons JC . 1995 Pharmacol. Rev. 47: 331–385

  • Green MH, Arlett CF, Cole J, Harcourt SA, Priestley A, Waugh AP, Stephens G, Beare DM, Brown NA, Shun-Shin GA . 1991 Int. J. Rad. Biol. 59: 749–765

  • Hill ME, MacLennan KA, Cunningham DC . 1996 Blood 88: 1046–1051

  • Jo M, Kim TH, Seol DW, Esplen JE, Dorko K, Billiar TR, Strom SC . 2000 Nat. Med. 6: 564–567

  • Juo P, Kuo CJ, Yuan J, Blenis J . 1998 Curr. Biol. 10: 1001–1008

  • Kirsch DG, Doseff A, Chau BN, Lim DS, de Souza-Pinto NC, Hansford R, Kastan MB, Lazebnik YA, Hardwick JM . 1999 J. Biol. Chem. 274: 21155–21161

  • Lowe SW, Schmitt EM, Smith SW, Osborne BA, Jacks T . 1993 Nature 362: 847–849

  • Luo X, Budihardjo I, Zou H, Slaughter C, Wang X . 1998 Cell 94: 481–490

  • Miyashita T, Reed JC . 1995 Cell 80: 293–299

  • Muzio M, Chinnaiyan AM, Kischkel FC, O'Rourke K, Shevchenko A, Ni J, Scaffidi C, Bretz JD, Zhang M, Gentz R, Mann M, Krammer PH, Peter ME, Dixit VM . 1996 Cell 85: 817–827

  • Nitsch R, Bechmann I, Deisz RA, Haas D, Lehmann TN, Wendling U, Zipp F . 2000 Lancet 356: 827–828

  • Rosse T, Olivier R, Monney L, Rager M, Conus S, Fellay I, Jansen B, Borner C . 1998 Nature 391: 496–499

  • Scaffidi C, Fulda S, Srinivasan A, Friesen C, Li F, Tomaselli KJ, Debatin KM, Krammer PH, Peter ME . 1998 EMBO J. 17: 1675–1687

  • Schneider P, Thome M, Burns K, Bodmer JL, Hofmann K, Kataoka T, Holler N, Tschopp J . 1997 Immunity 7: 831–836

  • Sheikh MS, Burns TF, Huang Y, Wu GS, Amundson S, Brooks KS, Fornace Jr AJ, el-Deiry WS . 1998 Cancer Res. 58: 1593–1598

  • Soengas MS, Alarcon RM, Yoshida H, Giaccia AJ, Hakem R, Mak TW, Lowe SW . 1999 Science 28: 156–159

  • Sprick MR, Weigand MA, Rieser E, Rauch CT, Juo P, Blenis J, Krammer PH, Walczak H . 2000 Immunity 12: 599–609

  • Steel GG, Peckham MJ . 1979 Int. J. Radiat. Oncol. Biol. Phys. 5: 85–91

  • Varfolomeev EE, Schuchmann M, Luria V, Chiannilkulchai N, Beckmann JS, Mett IL, Rebrikov D, Brodianski VM, Kemper OC, Kollet O, Lapidot T, Soffer D, Sobe T, Avraham KB, Goncharov T, Holtmann H, Lonai P, Wallach D . 1998 Immunity 9: 267–276

  • Walczak H, Miller RE, Ariail K, Gliniak B, Griffith TS, Kubin M, Chin W, Jones J, Woodward A, Le T, Smith C, Smolak P, Goodwin RG, Rauch CT, Schuh JCL, Lynch DH . 1999 Nat. Med. 5: 157–163

  • Walczak H, Bouchon A, Stahl H, Krammer PH . 2000 Cancer Res. 60: 3051–3057

  • Yin XM, Wang K, Gross A, Zhao Y, Zinkel S, Klocke B, Roth KA, Korsmeyer SJ . 1999 Nature 400: 886–891

Download references

Acknowledgements

We gratefully acknowledge the supply of reagents by Drs J Blenis J Yuan and K Bommert. The work presented here was supported by grants from the Deutsche Krebshilfe to C Belka, K Schulze-Osthoff and W Budach and a fortüne grant (#774-0-0) to C Belka.

Author information

Author notes

  1. K Schulze-Osthoff and W Budach: K Schulze-Osthoff and W Budach share equal senior authorship

Authors and Affiliations

  1. Department of Radiation Oncology, University of Tübingen (Germany), Hoppe-Seyler Str. 3, D-72076 Tübingen, Germany

    C Belka, B Schmid, P Marini, E Durand, J Rudner, H Faltin, M Bamberg & W Budach

  2. Department of Immunology and Cell Biology, Institute of Experimental Dermatology, University of Münster (Germany), Röntgenweg 21, D-48149 Muenster, Germany

    K Schulze-Osthoff

Authors
  1. C Belka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B Schmid
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P Marini
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E Durand
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J Rudner
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. H Faltin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M Bamberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. K Schulze-Osthoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. W Budach
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Belka, C., Schmid, B., Marini, P. et al. Sensitization of resistant lymphoma cells to irradiation-induced apoptosis by the death ligand TRAIL. Oncogene 20, 2190–2196 (2001). https://doi.org/10.1038/sj.onc.1204318

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204318

Keywords

This article is cited by

Search

Advanced search

Quick links