Knockdown of hepatoma-derived growth factor-related protein-3 induces apoptosis of H1299 cells via ROS-dependent and p53-independent NF-κB activation

Journal Article · Fri Jul 11 04:00:00 EDT 2014 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2014.05.039· OSTI ID:22416611

Yun, Hong Shik ^[1]; Baek, Jeong-Hwa ^[1]; Yim, Ji-Hye ^[1]; Lee, Su-Jae ^[2]; Lee, Chang-Woo ^[3]; Song, Jie-Young; Um, Hong-Duck; Park, Jong Kuk; Park, In-Chul ^[1]; Hwang, Sang-Gu ^[1]

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1. Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)
2. Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of)
3. Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of)

Highlights: • HRP-3 is a radiation- and anticancer drug-responsive protein in H1299 cells. • Depletion of HRP-3 induces apoptosis of radio- and chemoresistant H1299 cells. • Depletion of HRP-3 promotes ROS generation via inhibition of the Nrf2/HO-1 pathway. • ROS generation enhances NF-κB activity, which acts as an upstream signal in the c-Myc/Noxa apoptotic pathway. - 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.

• OSTI ID: 22416611
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 449; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANTINEOPLASTIC DRUGS
ANTIOXIDANTS
APOPTOSIS
BIOLOGICAL MARKERS
GROWTH FACTORS
HEPATOMAS
INHIBITION
LUNGS
OXYGEN
PHENOTYPE
RADIOSENSITIVITY
TUMOR CELLS