Betanodavirus B2 protein triggers apoptosis and necroptosis in lung cancer cells that suppresses autophagy
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Hsuan-Wen Chiu1, Yu-Chin Su1 and Jiann-Ruey Hong1,2
1Department of Biotechnology and Bioindustry, Laboratory of Molecular Virology and Biotechnology, Institute of Biotechnology, National Cheng Kung University, Tainan 701, Taiwan
2Department of Biotechnology and Bioindustry, National Cheng Kung University, Tainan 701, Taiwan
Jiann-Ruey Hong, email: email@example.com
Keywords: B2 protein, cell death, p53, autophagy, lung cancer cell
Received: July 27, 2017 Accepted: September 21, 2017 Published: October 06, 2017
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 (41RTFVISAHAA50). 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.
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