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

Hsuan Wen Chiu, Yu Chin Su, Jiann Ruey Hong

研究成果: Article同行評審

2 引文 斯高帕斯(Scopus)

摘要

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.

原文English
頁(從 - 到)94129-94141
頁數13
期刊Oncotarget
8
發行號55
DOIs
出版狀態Published - 2017 十一月 1

All Science Journal Classification (ASJC) codes

  • Oncology

指紋 深入研究「Betanodavirus B2 protein triggers apoptosis and necroptosis in lung cancer cells that suppresses autophagy」主題。共同形成了獨特的指紋。

引用此