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

Sangnam Oh, Daeho Kwon, Hyun Jeong Lee, Joonhee Kim, Eun Il Lee

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1517-1528
Number of pages12
JournalApoptosis
Volume15
Issue number12
DOIs
Publication statusPublished - 2010 Dec 1

Fingerprint

Cells
Apoptosis
Carcinoma
Pressure
Lung
Neoplasms
TNF-Related Apoptosis-Inducing Ligand
TNF-Related Apoptosis-Inducing Ligand Receptors
Membranes
Compressed Air
Compressed air
Cell death
Chorioallantoic Membrane
Caspases
Mechanical Stress
Hyperoxia
Antineoplastic Agents
Mitochondrial Membrane Potential
Tumors
Reactive Oxygen Species

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Clinical Biochemistry
  • Biochemistry, medical
  • Pharmaceutical Science
  • Pharmacology

Cite this

Role of elevated pressure in TRAIL-induced apoptosis in human lung carcinoma cells. / Oh, Sangnam; Kwon, Daeho; Lee, Hyun Jeong; Kim, Joonhee; Lee, Eun Il.

In: Apoptosis, Vol. 15, No. 12, 01.12.2010, p. 1517-1528.

Research output: Contribution to journalArticle

Oh, Sangnam ; Kwon, Daeho ; Lee, Hyun Jeong ; Kim, Joonhee ; Lee, Eun Il. / Role of elevated pressure in TRAIL-induced apoptosis in human lung carcinoma cells. In: Apoptosis. 2010 ; Vol. 15, No. 12. pp. 1517-1528.
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