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

Hsuan Wen Chiu, Yu Chin Su, Jiann Ruey Hong

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 languageEnglish
Pages (from-to)94129-94141
Number of pages13
JournalOncotarget
Volume8
Issue number55
DOIs
Publication statusPublished - 2017 Nov 1

All Science Journal Classification (ASJC) codes

  • Oncology

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