Role of elevated pressure in TRAIL-induced apoptosis in human lung carcinoma cells
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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.
KeywordsElevated 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).
- 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 16:1352–1361CrossRefPubMedGoogle 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 104:155–162CrossRefPubMedGoogle 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 5:157–163CrossRefPubMedGoogle 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 7:383–385CrossRefPubMedGoogle Scholar
- 24.Speit Gt, Dennog C, Radermacher P, Rothfuss A (2002) Genotoxicity of hyperbaric oxygen. Mutat Res/Rev Mutat Res 512:111–119Google 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 13:76–83CrossRefGoogle 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:e10376Google 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 9:82–88Google Scholar