, Volume 15, Issue 12, pp 1517–1528 | Cite as

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

  • Sangnam Oh
  • Daeho Kwon
  • Hyun Jeong Lee
  • Joonhee Kim
  • Eunil Lee
Original Paper


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.


Elevated pressure TNF-related apoptosis-inducing ligand (TRAIL) Apoptosis Cancer therapy 



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).


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Sangnam Oh
    • 1
    • 2
  • Daeho Kwon
    • 2
  • Hyun Jeong Lee
    • 3
  • Joonhee Kim
    • 1
    • 2
  • Eunil Lee
    • 1
    • 2
  1. 1.Cellular and Developmental Biology, Division of Biomedical ScienceSeoulKorea
  2. 2.Department of Preventive Medicine and Medical Research Center for Environmental Toxico-Genomics and Proteomics, College of MedicineKorea UniversitySeoulKorea
  3. 3.Avian Disease Laboratory, College of Veterinary MedicineKonkuk UniversitySeoulRepublic of Korea

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