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 (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.
| Original language | English |
|---|---|
| Pages (from-to) | 94129-94141 |
| Number of pages | 13 |
| Journal | Oncotarget |
| Volume | 8 |
| Issue number | 55 |
| DOIs | |
| Publication status | Published - 2017 Nov 1 |
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All Science Journal Classification (ASJC) codes
- Oncology
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Betanodavirus B2 protein triggers apoptosis and necroptosis in lung cancer cells that suppresses autophagy. / Chiu, Hsuan Wen; Su, Yu Chin; Hong, Jiann Ruey.
In: Oncotarget, Vol. 8, No. 55, 01.11.2017, p. 94129-94141.Research output: Contribution to journal › Article
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
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.
UR - http://www.scopus.com/inward/record.url?scp=85032931962&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85032931962&partnerID=8YFLogxK
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 -