Oncolytic Activity of Canine Distemper Virus in Human Ductal Breast Carcinoma Cells
Dhwani Jhala1, Neelam Nathani2,3, Madhvi Joshi2
1Gujarat Biotechnology Research Centre (GBRC), Department of Science and Technology, Government of Gujarat, Gandhinagar, India, scib2@gbrc.res.in.
Introduction:
Oncolytic virotherapy is a novel strategy for cancer treatment in humans and companion animals. Canine distemper virus (CDV) is known to induce apoptosis in tumor cells, thus serving as a potential candidate for oncolytic therapy. However, the mechanism of viral oncolytic activity is less studied and varies depending on the type of cancer and cell lines.
Methods:
In the present study, the susceptibility of the MCF-7 cell line to CDV infection was assessed using the CDV strain, which was confirmed previously through sequence analysis in the Vero cell line. The impact of CDV infection on cell proliferation and apoptosis was studied by evaluating the expression of four target genes including the myeloid cell leukemia 1 (MCL-1), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), transcription factor (SP1), and DNA (cytosine-5)-methyltransferase 3A (DNMT3A).
Results:
CDV replication in the cells induced cytopathic effect and decreased in the cell proliferation rates compared to the uninfected control. MCL-1, SP1, and PIK3R1 gene expression was down-regulated, while the expression of DNMT3A was up-regulated 3 days post-infection. The expression levels of the target genes suggest that CDV may be inducing the intrinsic apoptotic pathway in the cancer cell line.
Conclusion:
Overall, the results strongly propose CDV strain as a potential candidate for cancer therapy after detailed studies.
Insights
Canine distemper virus (CDV) shows potential as an oncolytic therapy by reducing cancer cell proliferation and inducing apoptosis. Gene expression changes suggest CDV activates the intrinsic apoptotic pathway in tumor cells.
Area of Science:
- Oncolytic virotherapy
- Cancer biology
- Molecular oncology
Background:
- Oncolytic virotherapy utilizes viruses to selectively target and destroy cancer cells.
- Canine distemper virus (CDV) demonstrates tumor cell apoptosis-inducing properties, making it a candidate for oncolytic therapy.
- The precise mechanisms of viral oncolytic activity across different cancer types remain under investigation.
Purpose of the Study:
- To assess the susceptibility of the MCF-7 cell line to Canine distemper virus (CDV) infection.
- To investigate the impact of CDV on cancer cell proliferation and apoptosis.
- To analyze the gene expression changes related to apoptosis following CDV infection.
Main Methods:
- MCF-7 cells were infected with a characterized CDV strain.
- Cell proliferation rates were measured post-infection.
- The expression levels of MCL-1, PIK3R1, SP1, and DNMT3A genes were evaluated to assess apoptosis induction.
Main Results:
- CDV replication led to a cytopathic effect and reduced MCF-7 cell proliferation compared to controls.
- Gene expression analysis revealed down-regulation of MCL-1, SP1, and PIK3R1, and up-regulation of DNMT3A three days post-infection.
- These gene expression patterns suggest CDV may trigger the intrinsic apoptotic pathway in cancer cells.
Conclusions:
- The studied CDV strain effectively reduces cancer cell proliferation and induces apoptosis.
- CDV shows promise as a potential oncolytic agent for cancer therapy.
- Further comprehensive studies are warranted to fully establish CDV's therapeutic potential.
Related Concept Videos
01:03Rous Sarcoma Virus (RSV) and Cancer
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
01:03Rous Sarcoma Virus (RSV) and Cancer
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...