Abstract
The high frequency of intrinsic resistance to TNF-related apoptosisinducing ligand (TRAIL) in tumor cell lines has necessitated the development of strategies to sensitize tumors to TRAIL-induced apoptosis. We previously showed that elevated pressure applied as a mechanical stressor enhanced TRAIL-mediated apoptosis in human lung carcinoma cells in vitro and in vivo. This study focused on the effect of elevated pressure on the sensitization of TRAIL-resistant cells and the underlying mechanism. We observed elevated pressure-induced sensitization to TRAIL-mediated apoptosis in Hep3B cells, accompanied by the activation of several caspases and the mitochondrial signaling pathway. Interestingly, the enhanced apoptosis induced by elevated pressure was correlated with suppression of extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) phosphorylation and CREB without any change to other MAPKs. Phosphorylation of Bcl-2-associated death promoter (BAD) also decreased, leading to inhibition of the mitochondrial pathway. To confirm whether the activation of pERK1/2 plays a key role in the TRAIL-sensitizing effect of elevated pressure, Hep3B cells were pre-treated with the ERK1/2-specific inhibitor PD98059 instead of elevated pressure. Co-treatment with PD98059 and TRAIL augmented TRAIL-induced apoptosis and decreased BAD phosphorylation. The inhibition of ERK1/2 activation by elevated pressure and PD98059 also reduced BH3 interacting-domain death agonist (BID), thereby amplifying apoptotic stress at the mitochondrial level. Our results suggest that elevated pressure enhances TRAIL-induced apoptosis of Hep3B cells via specific suppression of ERK1/2 activation among MAPKs.
References
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© 2015
Articles in the same Issue
- Elevated pressure enhanced TRAIL-induced apoptosis in hepatocellular carcinoma cells via ERK1/2-inactivation
- HsOrc4-dependent DNA remodeling of the ori-β DHFR replicator
- Is Iron Chelation Important in Preventing Glycation of Bovine Serum Albumin in Vitro?
- The transition of the 37-kDa laminin receptor (RPSA) to higher molecular weight species: SUMOylation or artifact?
- Mechanical strain affects some microRNA profiles in pre-oeteoblasts.
- Sphingosine-1-phosphate induces the migration and angiogenesis of EPCs through the Akt signaling pathway via sphingosine-1-phosphate receptor 3/platelet-derived growth factor receptor-β
- Bioinformatics-based molecular classification of Arthrobacter plasmids
- Ras Transformation Overrides a Proliferation Defect Induced by Tpm3.1 Knockout
- The advanced lipoxidation end product precursor malondialdehyde induces IL-17E expression and skews lymphocytes to the Th17 subset
- On Application of Langevin Dynamics in Logarithmic Potential to Model Ion Channel Gate Activity
- Superoxide Dismutase 2 Polymorphisms and Osteoporosis in Asian Indians: A Genetic Association Analysis
Articles in the same Issue
- Elevated pressure enhanced TRAIL-induced apoptosis in hepatocellular carcinoma cells via ERK1/2-inactivation
- HsOrc4-dependent DNA remodeling of the ori-β DHFR replicator
- Is Iron Chelation Important in Preventing Glycation of Bovine Serum Albumin in Vitro?
- The transition of the 37-kDa laminin receptor (RPSA) to higher molecular weight species: SUMOylation or artifact?
- Mechanical strain affects some microRNA profiles in pre-oeteoblasts.
- Sphingosine-1-phosphate induces the migration and angiogenesis of EPCs through the Akt signaling pathway via sphingosine-1-phosphate receptor 3/platelet-derived growth factor receptor-β
- Bioinformatics-based molecular classification of Arthrobacter plasmids
- Ras Transformation Overrides a Proliferation Defect Induced by Tpm3.1 Knockout
- The advanced lipoxidation end product precursor malondialdehyde induces IL-17E expression and skews lymphocytes to the Th17 subset
- On Application of Langevin Dynamics in Logarithmic Potential to Model Ion Channel Gate Activity
- Superoxide Dismutase 2 Polymorphisms and Osteoporosis in Asian Indians: A Genetic Association Analysis