TY - JOUR
T1 - Betanodavirus B2 protein triggers apoptosis and necroptosis in lung cancer cells that suppresses autophagy
AU - Chiu, Hsuan Wen
AU - Su, Yu Chin
AU - Hong, Jiann Ruey
N1 - Funding Information:
The authors are grateful to Dr. H. S. Lu (Department of Microbiology and Immunology of National Cheng Kung University, Tainan 701, Taiwan, ROC) for providing the A549 and H1299 cell lines. This work was supported by a grant (MOST 104-2313-B-006-003) awarded to Dr. Jainn-Ruey Hong from the Ministry of Science and Technology, Taiwan, Republic of China. This work was supported by a grant (MOST 104-2313-B-006-003) awarded to Dr. Jainn-Ruey Hong from the Ministry of Science and Technology, Taiwan, Republic of China.
Publisher Copyright:
© Chiu et al.
PY - 2017/11/1
Y1 - 2017/11/1
N2 - 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-a) 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.
AB - 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-a) 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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U2 - 10.18632/oncotarget.21588
DO - 10.18632/oncotarget.21588
M3 - Article
AN - SCOPUS:85032931962
VL - 8
SP - 94129
EP - 94141
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 55
ER -