M51R and Delta-M51 matrix protein of the vesicular stomatitis virus induce apoptosis in colorectal cancer cells

Gray, Zahra; Tabarraei, Alijan; Moradi, Abdolvahab; Kalani, Mohamad Reza

doi:10.1007/s11033-019-04799-3

Cited by 13 publications

(8 citation statements)

References 47 publications

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“…Kopecky et al., as well as Gaddy and Lyles, suggested that apoptosis induced by mutant M-protein is due to the expression of some new genes in the host cell that are responsible for mitochondrial cell switching death, whereas apoptosis caused by WT M-protein is due to global inhibition of host gene expression. 32 , 35 However, in one study examining the effect of different VSV M-proteins on host gene expression in human embryonic kidney BHK21 cells, it was reported that the substitution of Methionine 51 with Arginine weakened the apoptotic potential of M-protein to the minimum level and led to the halter caspase-3 induction. 36 …”

Section: Discussionmentioning

confidence: 99%

NEBL and AKT1 maybe new targets to eliminate the colorectal cancer cells resistance to oncolytic effect of vesicular stomatitis virus M-protein

Mamizadeh

Kalani

Parsania

et al. 2021

Molecular Therapy - Oncolytics

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This study compares the oncolytic effect of vesicular stomatitis virus (VSV) wild type and M51R M-protein on the colorectal tumors of different invasive intensity on SW480 and HCT116 cell lines and 114 fresh colorectal cancer primary cell cultures. Fresh tumor samples were divided into two groups of lower stages (I/II) and higher stages (III/IV) regarding the medical records. The presence of two mutations in the PIK3CA gene and the expression of NEBL and AKT1 genes were evaluated. The cells were transfected with a plasmid encoding VSV wild-type and M51R mutant M-protein. Results showed either wild type or M51R mutant can kill SW480 and stage I/II primary cultures while mutant M-protein had no apoptotic effects on HCT116 cells and stage III/IV primary cultures. NEBL and AKT1 expression were significantly higher in resistant cells. Elevated caspase-9 activity confirmed that the intrinsic apoptosis pathway is the reason for cell death in lower-stage cells. Different tumors from the same cancer exhibit different treatment sensitivity due to genetic difference. NEBL and AKT1 gene expression may be responsible for this difference, which may be the target of future investigations. Therefore, tumor staging should be considered in oncolytic viral treatment as an interfering factor.

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Section: Discussionmentioning

confidence: 99%

NEBL and AKT1 maybe new targets to eliminate the colorectal cancer cells resistance to oncolytic effect of vesicular stomatitis virus M-protein

Mamizadeh

Kalani

Parsania

et al. 2021

Molecular Therapy - Oncolytics

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“…Kopecky, as well as Gaddy, suggested that apoptosis induced by mutant M-protein is due to the expression of some new genes in the host cell that are responsible for mitochondrial cell switching death, whereas apoptosis is caused by wt M-protein is due to global inhibition of host gene expression (11,31,33). However, in one study examining the effect of different VSV M-proteins on host gene expression in human embryonic kidney BHK21 cells, it was reported that the substitution of Methionine 51 with Arginine weakened the apoptotic potential of M-protein to the minimum level and lead to the halter caspase-3 induction (34).…”

Section: Discussionmentioning

confidence: 99%

NEBL and AKT1 Maybe New Targets to Eliminate the Colorectal Cancer Cells Resistance to Oncolytic Effect of Vesicular Stomatitis Virus

Mamizadeh

Kalani

Parsania

et al. 2021

Preprint

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Background: Oncolytic virotherapy is a promising therapeutic approach for several cancers which however has been reported that is ineffective in some cases of the same cancer. A well-known oncolytic virus is the Vesicular stomatitis virus (VSV) due to activating the apoptosis mechanism in tumor cells through its Matrix (M) protein. This study compares the different invasive intensity Colorectal tumors for the oncolytic effect of VSV wild type (wt) and M51R M-protein.Methods: 114 fresh colorectal tumor primary cell cultures plus SW480 and HCT116 colorectal cancer cell lines were examined. Fresh tumor samples were divided into two groups of lower stages (I/II) and higher stages (III/IV) regarding the medical records. The presence of two mutations in the PIK3CA gene, and the expression of NEBL and AKT1 genes were evaluated to biologically compare the staging classification. The cell lines and the stable primary tissue cultures were transfected with a plasmid encoding VSV wild type and M51R mutant M-protein. Western blotting assay confirmed the expression of the protein. Results: MTT assay results showed either wild type or M51R mutant can kill SW480 and stage I/II primary cultures while mutant M-protein had no apoptotic effects on HCT116 cells and stage III/IV primary cultures. Morphological apoptosis features were observed by a phase-contrast microscope. NEBL and AKT1 expression were significantly higher in resistant cells. Elevated Caspase 9 activity confirmed that the intrinsic apoptosis pathway is the reason for cell death in SW480 cells. The apoptosis rate was quantified and reconfirmed by Annexin V FITC/PI multicolor flow-cytometry. Conclusions: Different tumors from the same cancer exhibit different sensitivity to M51R M-proteins due to genetic difference. NEBL and AKT1 gene expression may be responsible for this difference which maybe the target of future investigations. Therefore, tumor staging should be considered in oncolytic viral treatment as an interfering factor.

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“…Lal and Rajala have developed a recombinant measles virus harboring BNiP3, a pro-apoptotic gene of human origin, which as an oncolytic agent, has been shown to induce apoptosis in breast cancer cells in vitro ( Lal and Rajala, 2018 ). Recently, M51R and Delta-M51 matrix proteins of VSV induce apoptosis in colorectal cancer cells ( Gray et al., 2019 ). Proto-parvovirus H-1 induces lytic infection and apoptosis in vitro but fails to improve survival in vivo ( Lacroix et al., 2018 ).…”

Section: Oncolytic Virus-regulated Induction Of Apoptosis Of Tumor Cellsmentioning

confidence: 99%

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

Sun²,

Chen

et al. 2023

Front. Cell. Infect. Microbiol.

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Recent reports have revealed that oncolytic viruses (OVs) play a significant role in cancer therapy. The infection of OVs such as oncolytic vaccinia virus (OVV), vesicular stomatitis virus (VSV), parvovirus, mammalian reovirus (MRV), human adenovirus, Newcastle disease virus (NDV), herpes simplex virus (HSV), avian reovirus (ARV), Orf virus (ORFV), inactivated Sendai virus (ISV), enterovirus, and coxsackievirus offer unique opportunities in immunotherapy through diverse and dynamic pathways. This mini-review focuses on the mechanisms of OVs-mediated virotherapy and their effects on immunogenic cell death (ICD), apoptosis, autophagy and regulation of the immune system.

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M51R and Delta-M51 matrix protein of the vesicular stomatitis virus induce apoptosis in colorectal cancer cells

Cited by 13 publications

References 47 publications

NEBL and AKT1 maybe new targets to eliminate the colorectal cancer cells resistance to oncolytic effect of vesicular stomatitis virus M-protein

NEBL and AKT1 maybe new targets to eliminate the colorectal cancer cells resistance to oncolytic effect of vesicular stomatitis virus M-protein

NEBL and AKT1 Maybe New Targets to Eliminate the Colorectal Cancer Cells Resistance to Oncolytic Effect of Vesicular Stomatitis Virus

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

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