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Published on: November 11, 2016
Porcine circovirus type 2 ORF3 protein induces apoptosis in melanoma cells
Marina Teras1, Edda Viisileht1,2, Merlis Pahtma-Hall2
1Oncology, North Estonia Medical Centre, 19 J. Sütiste tee st, 13419, Tallinn, Estonia.
Background:
The current treatment of malignant melanoma is limited by the lack of effective therapeutic approaches, and alternative treatments are needed. Proliferative diseases such as melanoma and other cancers may be treatable by virally-encoded apoptotic proteins that are targeted to rapidly multiplying cells. Caspase-dependent apoptosis, that is frequently used in chemotherapy, can boost the cell proliferation that caspase-independent cell death does not.
Methods:
In the current study, the porcine circovirus type 2 (PCV2), proapoptotic protein ORF3 was expressed in mouse and human cancer cell lines, and its apoptotic activity was assessed.
Results:
Quantitative assessment of the apoptotic cells by flow cytometry showed that apoptotic cell death was significantly increased in ORF3-expressing malignant cells, compared to ORF3 non-expressing cells. Our data show that PCV2 ORF3 induces apoptosis in a caspase-3 and -8 independent manner. ORF3 expression seems to cause an increase in abnormal mitosis in B16F10 melanoma cells by interacting with centrosomes and thereby disrupting the formation of the mitotic spindle. In addition, we show that ORF3 of PCV2 also exhibits significant anti-tumor effects in vivo. Although the expression of Regulator of G protein Signaling (RGS)-16 by recipient mice inhibited the development of grafted melanoma in vivo, it was not required for the antitumoral activity of ORF3.
Conclusion:
PCV2 ORF3 causes abnormal mitosis in rapidly dividing cells and increases the apoptosis of cancer cells. Apoptin might, therefore, be considered to develop future antitumoral strategies.
Insights
Porcine circovirus 2 ORF3 protein induces apoptosis and abnormal mitosis in cancer cells, offering a potential new strategy for cancer treatment. This viral protein shows significant anti-tumor effects in vivo.
Area of Science:
- Oncology
- Virology
- Cell Biology
Background:
- Malignant melanoma and other cancers lack effective treatments, necessitating novel therapeutic strategies.
- Virally-encoded apoptotic proteins show promise for targeting rapidly proliferating cancer cells.
- Caspase-dependent apoptosis, common in chemotherapy, can paradoxically increase cell proliferation, unlike caspase-independent cell death.
Purpose of the Study:
- To investigate the apoptotic activity of the porcine circovirus type 2 (PCV2) proapoptotic protein ORF3 in cancer cells.
- To assess the potential of PCV2 ORF3 as an anti-cancer therapeutic agent.
Main Methods:
- Expression of PCV2 ORF3 in mouse and human cancer cell lines.
- Quantitative assessment of apoptotic cells using flow cytometry.
- In vivo studies to evaluate anti-tumor effects of ORF3.
Main Results:
- PCV2 ORF3 significantly increased apoptotic cell death in malignant cells.
- ORF3 induces apoptosis independently of caspase-3 and -8.
- ORF3 interacts with centrosomes, disrupting mitotic spindle formation and causing abnormal mitosis.
- PCV2 ORF3 demonstrated significant anti-tumor effects in vivo, independent of RGS-16 expression.
Conclusions:
- PCV2 ORF3 promotes abnormal mitosis and apoptosis in rapidly dividing cancer cells.
- ORF3 holds potential for the development of future anti-cancer therapeutic strategies.
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