Back to Search
Start Over
Betanodavirus B2 protein triggers apoptosis and necroptosis in lung cancer cells that suppresses autophagy
- Source :
- Oncotarget
- Publication Year :
- 2017
- Publisher :
- Impact Journals, LLC, 2017.
-
Abstract
- // Hsuan-Wen Chiu 1 , Yu-Chin Su 1 and Jiann-Ruey Hong 1, 2 1 Department of Biotechnology and Bioindustry, Laboratory of Molecular Virology and Biotechnology, Institute of Biotechnology, National Cheng Kung University, Tainan 701, Taiwan 2 Department of Biotechnology and Bioindustry, National Cheng Kung University, Tainan 701, Taiwan Correspondence to: Jiann-Ruey Hong, email: jrhong@mail.ncku.edu.tw Keywords: B2 protein, cell death, p53, autophagy, lung cancer cell Received: July 27, 2017 Accepted: September 21, 2017 Published: October 06, 2017 ABSTRACT The betanodavirus B2 protein targets the mitochondria and acts as a “death factor”, but its effect on lung cancer cells is unknown. We examined the effect of the B2 protein on triggering apoptosis or necroptosis via P53-dependent and P53-independent pathways and increased in suppression of autophagy. The B2 protein targets the mitochondria of A549 (P53 +/+ ) and H1299 (P53 —/— ) lung cancer cells due to a specific signal sequence ( 41 RTFVISAHAA 50 ). This triggers generation of reactive oxygen species within the mitochondria, and a minor stress response in A549 cells, but a strong stress response in H1299 cells. We examined the molecular mechanism of this cell death pathway, and found that B2 protein induces the P53/Bax-mediated apoptotic pathway in A549 cells, and that a P53 specific inhibitor (pifithrin-α) switches this response to RIP3-mediated necroptosis. On the other hand, B2 induces RIP3-mediated necroptosis pathway in H1299 cells, and a necroptosis inhibitor (necrostatin-1) switches this response to the apoptotic pathway. Both types of cell death signals inhibited autophagy via a tightly increased balance of beclin-1 and Bcl-2. Thus, B2 protein triggers P53-dependent apoptosis in A549 cells and ROS/RIP3-mediated necroptosis in H1299 cells, and crosstalk of these pathways limits initiation of autophagy. These findings provide new insights into the possible control and treatment of lung cancer.
- Subjects :
- p53
0301 basic medicine
autophagy
Programmed cell death
Necroptosis
Biology
Mitochondrion
03 medical and health sciences
0302 clinical medicine
medicine
Lung cancer
lung cancer cell
B2 protein
A549 cell
chemistry.chemical_classification
Reactive oxygen species
Autophagy
medicine.disease
Cell biology
cell death
030104 developmental biology
Oncology
chemistry
Apoptosis
030220 oncology & carcinogenesis
Cancer research
Research Paper
Subjects
Details
- ISSN :
- 19492553
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....5edc1d2701858325e44080768dd4fdeb