title: Knockdown of hepatoma-derived growth factor-related protein-3 induces apoptosis of H1299 cells via ROS-dependent and p53-independent NF-κB activation.
abstract: We previously identified hepatoma-derived growth factor-related protein-3 (HRP-3) as a radioresistant biomarker in p53 wild-type A549 cells and found that p53-dependent induction of the PUMA pathway was a critical event in regulating the radioresistant phenotype. Here, we found that HRP-3 knockdown regulates the radioresistance of p53-null H1299 cells through a distinctly different molecular mechanism. HRP-3 depletion was sufficient to cause apoptosis of H1299 cells by generating substantial levels of reactive oxygen species (ROS) through inhibition of the Nrf2/HO-1 antioxidant pathway. Subsequent, ROS-dependent and p53-independent NF-κB activation stimulated expression of c-Myc and Noxa proteins, thereby inducing the apoptotic machinery. Our results thus extend the range of targets for the development of new drugs to treat both p53 wild-type or p53-null radioresistant lung cancer cells.
authors.affiliation: Division of Radiation Cancer Biology, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea; Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Hong Shik
authors.initials: HS
authors.lastname: Yun
authors.affiliation: Division of Radiation Cancer Biology, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea; Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Republic of Korea.
authors.forename: Jeong-Hwa
authors.initials: JH
authors.lastname: Baek
authors.affiliation: Division of Radiation Cancer Biology, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea.
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Yim
authors.affiliation: Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Su-Jae
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Republic of Korea.
authors.forename: Chang-Woo
authors.initials: CW
authors.lastname: Lee
authors.affiliation: Division of Radiation Cancer Biology, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea.
authors.forename: Jie-Young
authors.initials: JY
authors.lastname: Song
authors.affiliation: Division of Radiation Cancer Biology, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea.
authors.forename: Hong-Duck
authors.initials: HD
authors.lastname: Um
authors.affiliation: Division of Radiation Cancer Biology, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea.
authors.forename: Jong Kuk
authors.initials: JK
authors.lastname: Park
authors.affiliation: Division of Radiation Cancer Biology, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea.
authors.forename: In-Chul
authors.initials: IC
authors.lastname: Park
authors.affiliation: Division of Radiation Cancer Biology, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea. Electronic address: sgh63@kcch.re.kr.
authors.forename: Sang-Gu
authors.initials: SG
authors.lastname: Hwang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins; D055785:Gene Knockdown Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008175:Lung Neoplasms / Q000473:pathology* / Q000532:radiotherapy; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; C498539:HDGFL3 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53
keywords: H1299 cells; HRP-3; Myc/Noxa signaling; NF-κB; ROS