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Betanodavirus B2 protein triggers apoptosis and necroptosis in lung cancer cells that suppresses autophagy

Authors :
Jiann Ruey Hong
Hsuan Wen Chiu
Yu Chin Su
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.

Details

ISSN :
19492553
Volume :
8
Database :
OpenAIRE
Journal :
Oncotarget
Accession number :
edsair.doi.dedup.....5edc1d2701858325e44080768dd4fdeb