Skip to main content
SpringerLink
Log in

Role of elevated pressure in TRAIL-induced apoptosis in human lung carcinoma cells

  • Original Paper
  • Published:
Apoptosis Aims and scope Submit manuscript

Abstract

TNF-related apoptosis-inducing ligand (TRAIL, Apo2L) is a promising anticancer agent with high specificity for cancer cells. Many strategies have been proposed to enhance the sensitivity of cancer cells to TRAIL-mediated apoptosis, including the use of combination treatment with conventional cancer therapies. However, few reports have evaluated the effects of TRAIL in combination with mechanical stress, which can also cause apoptosis of cancer cells. In the present study, we describe a custom-designed culture system that delivers two atmospheres of elevated pressure (EP) by using compressed air, and which enhances the sensitivity of cancer cells to TRAIL-mediated apoptosis. The combination of TRAIL and EP significantly increased apoptosis of human H460 lung cancer cells more than hyperbaric normoxia or normobaric mild hyperoxia. EP-potentiating TRAIL-mediated apoptosis of H460 cells was accompanied by up-regulated death receptor 5 (DR5), activation of caspases, decreased mitochondrial membrane potential, and reactive oxygen species production. We also observed EP-induced sensitization of TRAIL-mediated apoptosis in other cancer cell types. In contrast, human normal cells showed no DNA damage or cell death when exposed to the combined treatment. In a chicken chorioallantoic membrane model, EP enhanced TRAIL-mediated apoptosis of tumors that developed from transplanted H460 cells. Collectively, EP enhanced TRAIL-induced apoptosis of human lung carcinoma cells in vitro and in vivo. These findings suggest that EP is a mechanical and physiological stimulus that might have utility as a sensitizing tool for cancer therapy.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Ferreira CG, Epping M, Kruyt FA, Giaccone G (2002) Apoptosis: target of cancer therapy. Clin Cancer Res 8:2024–2034

    CAS  PubMed  Google Scholar 

  2. French LE, Tschopp J (1999) The TRAIL to selective tumor death. Nat Med 5:146–147

    Article  CAS  PubMed  Google Scholar 

  3. Kischkel FC, Lawrence DA, Chuntharapai A, Schow P, Kim KJ, Ashkenazi A (2000) Apo2L/TRAIL-dependent recruitment of endogenous FADD and caspase-8 to death receptors 4 and 5. Immunity 12:611–620

    Article  CAS  PubMed  Google Scholar 

  4. Srivastava RK (2001) TRAIL/Apo-2L: mechanisms and clinical applications in cancer. Neoplasia 3:535–546

    Article  CAS  PubMed  Google Scholar 

  5. Johnstone RW, Frew AJ, Smyth MJ (2008) The TRAIL apoptotic pathway in cancer onset, progression and therapy. Nat Rev Cancer 8:782–798

    Article  CAS  PubMed  Google Scholar 

  6. Hajji N, Wallenborg K, Vlachos P, Nyman U, Hermanson O, Joseph B (2007) Combinatorial action of the HDAC inhibitor trichostatin A and etoposide induces caspase-mediated AIF-dependent apoptotic cell death in non-small cell lung carcinoma cells. Oncogene 27:3134–3144

    Article  PubMed  Google Scholar 

  7. Persaud SD, Mireles JR, Basu A (2009) Proteolytic Cleavage of p70 Ribosomal S6 Kinase by Caspase-3 during DNA damage-induced apoptosis. Biochemistry 48:1474–1480

    Article  PubMed  Google Scholar 

  8. Voortman J, Resende TP, Abou El Hassan MAI, Giaccone G, Kruyt FAE (2007) TRAIL therapy in non small cell lung cancer cells: sensitization to death receptor-mediated apoptosis by proteasome inhibitor bortezomib. Mol Cancer Ther 6:2103–2112

    Article  CAS  PubMed  Google Scholar 

  9. Luster TA, Carrell JA, McCormick K, Sun D, Humphreys R (2009) Mapatumumab and lexatumumab induce apoptosis in TRAIL-R1 and TRAIL-R2 antibody-resistant NSCLC cell lines when treated in combination with bortezomib. Mol Cancer Ther 8:292–302

    Article  CAS  PubMed  Google Scholar 

  10. Ozoren N, Kim K, Burns TF, Dicker DT, Moscioni AD, El-Deiry WS (2000) The Caspase 9 inhibitor Z-LEHD-FMK protects human liver cells while permitting death of cancer cells exposed to tumor necrosis factor-related apoptosis-inducing ligand. Cancer Res 60:6259–6265

    CAS  PubMed  Google Scholar 

  11. Wilson TR, Redmond KM, McLaughlin KM, Crawford N, Gately K, O’Byrne K, Le-Clorrenec C, Holohan C, Fennell DA, Johnston PG, Longley DB (2009) Procaspase 8 overexpression in non-small-cell lung cancer promotes apoptosis induced by FLIP silencing. Cell Death Differ 16:1352–1361

    Article  CAS  PubMed  Google Scholar 

  12. 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) Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest 104:155–162

    Article  CAS  PubMed  Google Scholar 

  13. 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 JC, Lynch DH (1999) Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo. Nat Med 5:157–163

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  15. Elrod HA, Sun SY (2008) Modulation of death receptors by cancer therapeutic agents. Cancer Biol Ther 7:163–173

    CAS  PubMed  Google Scholar 

  16. Chen JJ, Chou CW, Chang YF, Chen CC (2008) Proteasome inhibitors enhance TRAIL-induced apoptosis through the intronic regulation of DR5: involvement of NF-kappa B and reactive oxygen species-mediated p53 activation. J Immunol 180:8030–8039

    CAS  PubMed  Google Scholar 

  17. Yodkeeree S, Sung B, Limtrakul P, Aggarwal BB (2009) Zerumbone enhances TRAIL-induced apoptosis through the induction of death receptors in human colon cancer cells: evidence for an essential role of reactive oxygen species. Cancer Res 69:6581–6589

    Article  CAS  PubMed  Google Scholar 

  18. Daruwalla J, Christophi C (2006) Hyperbaric oxygen therapy for malignancy: a review. World J Surg 30:2112–2131

    Article  PubMed  Google Scholar 

  19. Bennett M, Feldmeier J, Smee R, Milross C (2008) Hyperbaric oxygenation for tumour sensitisation to radiotherapy: a systematic review of randomised controlled trials. Cancer Treat Rev 34:577–591

    Article  CAS  PubMed  Google Scholar 

  20. Park WH, Han YW, Kim SH, Kim SZ (2007) An ROS generator, antimycin A, inhibits the growth of HeLa cells via apoptosis. J Cell Biochem 102:98–109

    Article  CAS  PubMed  Google Scholar 

  21. Henk JM, Kunkler PB, Smith CW (1977) Radiotherapy and hyperbaric oxygen in head and neck cancer. Final report of first controlled clinical trial. Lancet 2:101–103

    Article  CAS  PubMed  Google Scholar 

  22. McMillan T, Calhoun KH, Mader JT, Stiernberg CM, Rajaraman S (1989) The effect of hyperbaric oxygen therapy of oral mucosal carcinoma. Laryngoscope 99:241–244

    Article  CAS  PubMed  Google Scholar 

  23. Kumar B, Koul S, Khandrika L, Meacham RB, Koul HK (2008) Oxidative stress is inherent in prostate cancer cells and is required for aggressive phenotype. Cancer Res 68:1777–1785

    Article  CAS  PubMed  Google Scholar 

  24. Speit Gt, Dennog C, Radermacher P, Rothfuss A (2002) Genotoxicity of hyperbaric oxygen. Mutat Res/Rev Mutat Res 512:111–119

    CAS  Google Scholar 

  25. Rutkowski JM, Swartz MA (2007) A driving force for change: interstitial flow as a morphoregulator. Trends Cell Biol 17:44–50

    Article  CAS  PubMed  Google Scholar 

  26. Jain RK (2005) Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307:58–62

    Article  CAS  PubMed  Google Scholar 

  27. Healey C, Forgione P, Lounsbury KM, Corrow K, Osler T, Ricci MA, Stanley A (2003) A new in vitro model of venous hypertension: the effect of pressure on dermal fibroblasts. J Vasc Surg 38:1099–1105

    Article  PubMed  Google Scholar 

  28. Oh S, Lee E, Lee J, Lim Y, Kim J, Woo S (2008) Comparison of the effects of 40% oxygen and two atmospheric absolute air pressure conditions on stress-induced premature senescence of normal human diploid fibroblasts. Cell Stress Chaperones 13:447–458

    Article  CAS  PubMed  Google Scholar 

  29. Vande Berg JS, Rose MA, Haywood-Reid PL, Rudolph R, Payne WG, Robson MC (2005) Cultured pressure ulcer fibroblasts show replicative senescence with elevated production of plasmin, plasminogen activator inhibitor-1, and transforming growth factor-beta1. Wound Repair Regen 13:76–83

    Article  Google Scholar 

  30. Stanley AC, Fernandez NN, Lounsbury KM, Corrow K, Osler T, Healey C, Forgione P, Shackford SR, Ricci MA (2005) Pressure-induced cellular senescence: a mechanism linking venous hypertension to venous ulcers. J Surg Res 124:112–117

    Article  PubMed  Google Scholar 

  31. von Zglinicki T, Saretzki G, Docke W, Lotze C (1995) Mild hyperoxia shortens telomeres and inhibits proliferation of fibroblasts: a model for senescence? Exp Cell Res 220:186–193

    Article  Google Scholar 

  32. Ferreira CG, Span SW, Peters GJ, Kruyt FA, Giaccone G (2000) Chemotherapy triggers apoptosis in a caspase-8-dependent and mitochondria-controlled manner in the non-small cell lung cancer cell line NCI-H460. Cancer Res 60:7133–7141

    CAS  PubMed  Google Scholar 

  33. Joseph B, Lewensohn R, Zhivotovsky B (2000) Role of apoptosis in the response of lung carcinomas to anti-cancer treatment. Ann N Y Acad Sci 926:204–216

    Article  CAS  PubMed  Google Scholar 

  34. Kunzi-Rapp K, Genze F, Kufer R, Reich E, Hautmann RE, Gschwend JE (2001) Chorioallantoic membrane assay: vascularized 3-dimensional cell culture system for human prostate cancer cells as an animal substitute model. J Urol 166:1502–1507

    Article  CAS  PubMed  Google Scholar 

  35. Chin WW, Heng PW, Olivo M (2007) Chlorin e6—polyvinylpyrrolidone mediated photosensitization is effective against human non-small cell lung carcinoma compared to small cell lung carcinoma xenografts. BMC Pharmacol 7:15

    Article  PubMed  Google Scholar 

  36. Krueger A, Baumann S, Krammer PH, Kirchhoff S (2001) FLICE-inhibitory proteins: regulators of death receptor-mediated apoptosis. Mol Cell Biol 21:8247–8254

    Article  CAS  PubMed  Google Scholar 

  37. Kim Y, Suh N, Sporn M, Reed JC (2002) An inducible pathway for degradation of FLIP protein sensitizes tumor cells to TRAIL-induced apoptosis. J Biol Chem 277:22320–22329

    Article  CAS  PubMed  Google Scholar 

  38. Chang L, Kamata H, Solinas G, Luo JL, Maeda S, Venuprasad K, Liu YC, Karin M (2006) The E3 ubiquitin ligase itch couples JNK activation to TNFalpha-induced cell death by inducing c-FLIP(L) turnover. Cell 124:601–613

    Article  CAS  PubMed  Google Scholar 

  39. Kauh J, Fan S, Xia M, Yue P, Yang L, Khuri FR, Sun SY (2010) c-FLIP degradation mediates sensitization of pancreatic cancer cells to TRAIL-induced apoptosis by the histone deacetylase inhibitor LBH589. PLoS One 5:e10376

    Google Scholar 

  40. Chowdhury F, Na S, Li D, Poh YC, Tanaka TS, Wang F, Wang N (2010) Material properties of the cell dictate stress-induced spreading and differentiation in embryonic stem cells. Nat Mater 9:82–88

    Google Scholar 

  41. Engler AJ, Sen S, Sweeney HL, Discher DE (2006) Matrix elasticity directs stem cell lineage specification. Cell 126:677–689

    Article  CAS  PubMed  Google Scholar 

  42. Cheng G, Tse J, Jain RK, Munn LL (2009) Micro-environmental mechanical stress controls tumor spheroid size and morphology by suppressing proliferation and inducing apoptosis in cancer cells. PLoS One 4:e4632

    Article  PubMed  Google Scholar 

  43. Stanley AC, Lounsbury KM, Corrow K, Callas PW, Zhar R, Howe AK, Ricci MA (2005) Pressure elevation slows the fibroblast response to wound healing. J Vasc Surg 42:546–551

    Article  PubMed  Google Scholar 

  44. Eken A, Aydin A, Sayal A, Ustundag A, Duydu Y, Dundar K (2005) The effects of hyperbaric oxygen treatment on oxidative stress and SCE frequencies in humans. Clin Biochem 38:1133–1137

    Article  CAS  PubMed  Google Scholar 

  45. Kwon D, Choi K, Choi C, Benveniste EN (2008) Hydrogen peroxide enhances TRAIL-induced cell death through up-regulation of DR5 in human astrocytic cells. Biochem Biophys Res Commun 372:870–874

    Article  CAS  PubMed  Google Scholar 

  46. Hunter AM, LaCasse EC, Korneluk RG (2007) The inhibitors of apoptosis (IAPs) as cancer targets. Apoptosis 12:1543–1568

    Article  CAS  PubMed  Google Scholar 

  47. Chawla-Sarkar M, Bae SI, Reu FJ, Jacobs BS, Lindner DJ, Borden EC (2004) Downregulation of Bcl-2, FLIP or IAPs (XIAP and survivin) by siRNAs sensitizes resistant melanoma cells to Apo2L/TRAIL-induced apoptosis. Cell Death Differ 11:915–923

    Article  CAS  PubMed  Google Scholar 

  48. Kumar S, Weaver VM (2009) Mechanics, malignancy, and metastasis: the force journey of a tumor cell. Cancer Metastasis Rev 28:113–127

    Article  PubMed  Google Scholar 

  49. Nicolson T (2005) Fishing for key players in mechanotransduction. Trends Neurosci 28:140–144

    Article  CAS  PubMed  Google Scholar 

  50. O’Neil RG, Heller S (2005) The mechanosensitive nature of TRPV channels. Pflugers Arch 451:193–203

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work (20090091416) was supported by a grant from the Basic Science Research Program of the National Research Foundation of Korea (NRF) funded by the Korea government (MEST).

Author information

Authors and Affiliations

  1. Cellular and Developmental Biology, Division of Biomedical Science, Seoul, Korea

    Sangnam Oh, Joonhee Kim & Eunil Lee

  2. Department of Preventive Medicine and Medical Research Center for Environmental Toxico-Genomics and Proteomics, College of Medicine, Korea University, Anam-dong 5ga 126-1, Seongbuk-gu, Seoul, 136-705, Korea

    Sangnam Oh, Daeho Kwon, Joonhee Kim & Eunil Lee

  3. Avian Disease Laboratory, College of Veterinary Medicine, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul, 143-701, Republic of Korea

    Hyun Jeong Lee

Authors
  1. Sangnam Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daeho Kwon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hyun Jeong Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Joonhee Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Eunil Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eunil Lee.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Oh, S., Kwon, D., Lee, H.J. et al. Role of elevated pressure in TRAIL-induced apoptosis in human lung carcinoma cells. Apoptosis 15, 1517–1528 (2010). https://doi.org/10.1007/s10495-010-0525-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10495-010-0525-5

Keywords

Search

Navigation