Transient activation of the PI3K/Akt pathway promotes Newcastle disease virus replication and enhances anti-apoptotic signaling responses

Kang, Yinfeng; Yuan, Runyu; Zhao, Xiaqiong; Xiang, Bin; Gao, Shimin; Gao, Pei; Xu, Daohua; Feng, Minsha; Li, Yanling; Xie, Peng; Li, Yulian; Gao, Xiaoyi; Ren, Tao

doi:10.18632/oncotarget.15796

Cited by 28 publications

(17 citation statements)

References 44 publications

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“…Further our results showed a decrease in the levels of p-Akt and p-GSK-3β upon NDV infection. Earlier reports suggest that NDV infection decreases p-Akt, however, its effect on GSK-3β has not been explored 63 . It has also been reported that GSK-3β regulates β-catenin level in cells 64 .…”

Section: Discussionmentioning

confidence: 98%

Newcastle disease virus mediated apoptosis and migration inhibition of human oral cancer cells: A probable role of β-catenin and matrix metalloproteinase-7

Morla

Kumar

2019

Sci Rep

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Cancer cell metastasis and its dissemination are most enigmatic and challenging aspects in the development of its therapeutics. Newcastle disease virus (NDV) is a well-studied avian paramyxovirus frequently isolated from birds and rarely from mammals. Since the first report of its oncolytic property, many NDV strains were studied for its effect in various cancer cells. In the present study, NDV strain Bareilly was characterized for its apoptotic potential and migration inhibition in human oral cancer cells. The NDV mediated apoptosis was confirmed by flow cytometry, DNA laddering, and immunoblotting. Moreover, NDV decreased the mitochondrial membrane potential suggesting an intrinsic pathway of apoptosis in oral cancer cells. NDV infection in oral cancer cells results in migration inhibition by a reduction in levels of MMP-7. MMP-7 is one of the key target genes of β-catenin. While overexpression of MMP-7 reversed the inhibitory effect of NDV mediated migration suggested its possible involvement. Wnt/β-catenin is an essential pathway for cell growth, differentiation, and metastasis. The involvement of the Wnt/β-catenin pathway in NDV infection has never been reported. Our results showed that NDV dysregulates Wnt/β-catenin by down-regulation of p-Akt and p-GSK3β leading to degradation of β-catenin. Furthermore, NDV infection leads to a reduction in cytoplasmic and nuclear levels of β-catenin. The study will provide us with a better insight into the molecular mechanism of NDV mediated oncolysis and the key cellular partners involved in the process.

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Section: Discussionmentioning

confidence: 98%

Newcastle disease virus mediated apoptosis and migration inhibition of human oral cancer cells: A probable role of β-catenin and matrix metalloproteinase-7

Morla

Kumar

2019

Sci Rep

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“…However, for the regulation of apoptosis and the cell cycle, research has focused on the PI3K/AKT signal pathway. Studies have found that the PI3K/AKT signaling pathway can control expression of Bad [15], caspase-9, Par 4 [16], p53 [17], and other factors, which prevents the mitochondrial apoptosis [18]. In addition, it can also activate the protein kinases of the cell cycle, increase the expression of cell cycle proteins, and promote cell cycle progression, cell proliferation, and differentiation, which subsequently promote tumor development [19].…”

Section: Discussionmentioning

confidence: 99%

Raddeanin A Induces Apoptosis and Cycle Arrest in Human HCT116 Cells through PI3K/AKT Pathway Regulation In Vitro and In Vivo

Meng

Teng

Jiang

2019

Evidence-Based Complementary and Alternative Medicine

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This study aimed to investigate the in vitro and in vivo effects of Raddeanin A on apoptosis and the cell cycle in the human colorectal cell line, HCT116, and to explore the possible underlying mechanisms of action. We found the growth inhibition rate gradually increased as the drug concentration increased via the 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, which indicated that Raddeanin A significantly inhibited the growth of HCT116 cells. Flow cytometry (FCM) showed that Raddeanin A concentration-dependently induced apoptosis in HCT116 cells. In addition, the percentage of cells in the G0/G1 phase was noticeably increased, which indicated that Raddeanin A blocked cell cycle progression in HCT116 cells and caused arrest in the G0/G1 phase. Moreover, the expression of proteins involved in the PI3K/AKT signaling pathway (e.g., p-PI3K and p-AKT) was decreased. The results showed that in vivo revealed that Raddeanin A significantly inhibited tumor growth in an HCT116-xenografted mouse model; apoptotic cells were also detected in the tumor tissue. The expression of the tissue proteins cyclinD1, cyclinE, p-PI3K, and p-AKT was decreased. The above results show that the Raddeanin A exerted a strong antitumor effect in the human colorectal cell line HCT116 both in vitro and in vivo. This effect may be caused by the induction of apoptosis and cycle arrest achieved through PI3K/AKT signaling pathway regulation.

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“…Although previous studies have demonstrated that NDV infection induces apoptosis and autophagy [ 19 – 23 ], their role during NDV infection is unknown. Therefore, the objective of our study was to investigate the roles of apoptosis and autophagy during NDV infection.…”

Section: Introductionmentioning

confidence: 99%

Newcastle disease virus-induced autophagy mediates antiapoptotic signaling responses in vitro and in vivo

et al. 2017

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In this study, we investigated the role of autophagy and apoptosis in Newcastle disease virus (NDV)-infected chicken cells and tissues. NDV-infected and starvation-induced chick embryo fibroblasts (CEF) cells showed higher autophagosome formation than mock-infected CEF cells on transmission electron microscopy. The NDV-infected CEF cells showed enhanced conversion of microtubule-associated protein 1 light chain 3-I (LC3-I) to LC3-II and degradation of p62/SQSTM1. The diminished conversion of LC3-I to LC3-II and cleaved caspase 3 and poly (ADP-ribose) polymerase (PARP) in ultraviolet-inactivated NDV-infected cells suggested that autophagosome formation was necessary for NDV replication. Inhibition of autophagy by chloroquine (CQ) enhanced apoptosis resulting in increased cleavage of caspase 3 and PARP and AnnexinV/propidium iodide staining. Autophagy induction by rapamycin resulted in upregulation of all autophagy-related genes except Beclin 1, anti-apoptosis factors, and proinflammatory cytokines in the NDV-infected spleen and lung tissues. Subsequently, decreased apoptosis was observed in NDV-infected spleens and lungs than mock-infected organs. The pan-caspase inhibitor ZVAD-FMK promoted conversion of LC3-I to LC3-II, the degradation of p62/SQSTM1, NDV replication and cell viability by inhibiting apoptosis. Our study demonstrates that apoptosis inhibition enhances autophagy and promoted cell survival and NDV replication.

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Transient activation of the PI3K/Akt pathway promotes Newcastle disease virus replication and enhances anti-apoptotic signaling responses

Abstract: ABSTRACT

Cited by 28 publications

References 44 publications

Newcastle disease virus mediated apoptosis and migration inhibition of human oral cancer cells: A probable role of β-catenin and matrix metalloproteinase-7

Newcastle disease virus mediated apoptosis and migration inhibition of human oral cancer cells: A probable role of β-catenin and matrix metalloproteinase-7

Raddeanin A Induces Apoptosis and Cycle Arrest in Human HCT116 Cells through PI3K/AKT Pathway Regulation In Vitro and In Vivo

Newcastle disease virus-induced autophagy mediates antiapoptotic signaling responses in vitro and in vivo

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