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

Abstract

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.

Engineered Human Adipose Stem-Cell-Derived Exosomes Loaded with miR-21-5p to Promote Diabetic Cutaneous Wound Healing

“…Our further analysis revealed that E-exos can activate Wnt/β-catenin signaling and upregulate the expression of MMP-7. MMP-7 is a crucial member of the matrix metalloproteinase (MMP) family, and it is involved in cell invasion of various cancers. , In the process of re-epithelialization of the wound, MMPs promote the breakdown of collagen or other structural compounds and, therefore, play an indispensable role in the movement of keratinocytes . MMP deletion damages the migration of cells and results in wound-healing defects .…”

CD44 targeted delivery of oncolytic Newcastle disease virus encapsulated in thiolated chitosan for sustained release in cervical cancer: a targeted immunotherapy approach

“…Cells were incubated with virus for 2 hours, followed by washing with DMEM media to remove unattached virus. Cells were then incubated at 37°C and 5% CO 2 for 3 days ( 27 ).…”

Oncolytic viruses-modulated immunogenic cell death, apoptosis and autophagy linking to virotherapy and cancer immune response

“…Furthermore, TRAIL-armed oncolytic poxvirus inhibits lung cancer cells by inducing apoptosis ( Hu et al., 2018 ). NDV decreased mitochondrial membrane potential, suggesting an intrinsic pathway of apoptosis in oral cancer cells ( Morla et al., 2019 ).…”