title: Canine parvovirus NS1 protein exhibits anti-tumor activity in a mouse mammary tumor model.
abstract: Many viral proteins have the ability to kill tumor cells specifically without harming the normal cells. These proteins, on ectopic expression, cause lysis or induction of apoptosis in the target tumor cells. Parvovirus NS1 is one of such proteins, which is known to kill high proliferating tumor cells. In the present study, we assessed the apoptosis inducing ability of canine parvovirus type 2 NS1 protein (CPV2.NS1) in vitro in 4T1 cells, and found it to cause significant cell death due to induction of apoptosis through intrinsic or mitochondrial pathway. Further, we also evaluated the oncolytic activity of CPV2.NS1 protein in a mouse mammary tumor model. The results suggested that CPV2.NS1 was able to inhibit the growth of 4T1 induced mouse mammary tumor as indicated by significantly reduced tumor volume, mitotic, AgNOR and PCNA indices. Further, inhibition of tumor growth was found to be because of induction of apoptosis in the tumor cells, which was evident by a significant increase in the number of TUNEL positive cells. Further, CPV2.NS1 was also able to stimulate the immune cells against the tumor antigens as indicated by the increased CD4+ and CD8+ counts in the blood of CVP2.NS1 treated mice. Further optimization of the delivery of NS1 protein and use of an adjuvant may further enhance its anti-tumor activity.
authors.affiliation: Molecular Biology Lab, Division of Veterinary Biotechnology, Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, UP, India. Electronic address: shishirgupta.biotech@gmail.com.
authors.forename: Shishir Kumar
authors.initials: SK
authors.lastname: Gupta
authors.affiliation: Animal Biochemistry Division, Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, UP, India.
authors.forename: Pavan Kumar
authors.initials: PK
authors.lastname: Yadav
authors.affiliation: Molecular Biology Lab, Division of Veterinary Biotechnology, Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, UP, India.
authors.forename: Ravi Kumar
authors.initials: RK
authors.lastname: Gandham
authors.affiliation: Molecular Biology Lab, Division of Veterinary Biotechnology, Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, UP, India.
authors.forename: A P
authors.initials: AP
authors.lastname: Sahoo
authors.affiliation: Molecular Biology Lab, Division of Veterinary Biotechnology, Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, UP, India.
authors.forename: D R
authors.initials: DR
authors.lastname: Harish
authors.affiliation: Molecular Biology Lab, Division of Veterinary Biotechnology, Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, UP, India.
authors.forename: Arvind Kumar
authors.initials: AK
authors.lastname: Singh
authors.affiliation: Molecular Biology Lab, Division of Veterinary Biotechnology, Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, UP, India. Electronic address: aktiwari63@yahoo.com.
authors.forename: A K
authors.initials: AK
authors.lastname: Tiwari
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism*; D017209:Apoptosis; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000235:genetics; D045744:Cell Line, Tumor; D015870:Gene Expression; D008325:Mammary Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D051379:Mice; D017993:Parvovirus, Canine / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome; D017361:Viral Nonstructural Proteins / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D011994:Recombinant Proteins; D017361:Viral Nonstructural Proteins
keywords: Anti-tumor immune response; Apoptosis; Breast cancer; Mammary tumor; NS1; Parvovirus