Depletion of hepatoma-derived growth factor-related protein-3 induces apoptotic sensitization of radioresistant A549 cells via reactive oxygen species-dependent p53 activation
- Title
- Depletion of hepatoma-derived growth factor-related protein-3 induces apoptotic sensitization of radioresistant A549 cells via reactive oxygen species-dependent p53 activation
- Author
- 이수재
- Keywords
- A549 cells; HRP-3; Nrf2/HO-1; p53/PUMA; ROS
- Issue Date
- 2013-09
- Publisher
- Elsevier Science B.V., Amsterdam
- Citation
- Biochemical and biophysical research communications, Vol.439 No.3 [2013], 333-339
- Abstract
- Biomarkers based on functional signaling have the potential to provide greater insight into the pathogenesis of cancer and may offer additional targets for anticancer therapeutics. Here, we identified hepatoma-derived growth factor-related protein-3 (HRP-3) as a radioresistance-related gene and characterized the molecular mechanism by which its encoded protein regulates the radio- and chemoresistant phenotype of lung cancer-derived A549 cells. Knockdown of HRP-3 promoted apoptosis of A549 cells and potentiated the apoptosis-inducing action of radio- and chemotherapy. This increase in apoptosis was associated with a substantial generation of reactive oxygen species (ROS) that was attributable to inhibition of the Nrf2/HO-1 antioxidant pathway and resulted in enhanced ROS-dependent p53 activation and p53-dependent expression of PUMA (p53 upregulated modulator of apoptosis). Therefore, the HRP-3/Nrf2/HO-1/ ROS/p53/PUMA cascade is an essential feature of the A549 cell phenotype and a potential radiotherapy target, extending the range of targets in multimodal therapies against lung cancer. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved.
- URI
- https://www.sciencedirect.com/science/article/pii/S0006291X13014447?via%3Dihubhttp://hdl.handle.net/20.500.11754/44717
- ISSN
- 0006-291X
- DOI
- 10.1016/j.bbrc.2013.08.086
- Appears in Collections:
- COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
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