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Published on: April 23, 2014
Anticancer effect of inactivated Sendai virus strain Tianjin on human osteosarcoma HOS cells
Qing Li1, Huachong Ma2, Shuya Sun
1Department of Pathogenic Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. liqing2@tmu.edu.cn.
Abstract:
Ultraviolet-inactivated Sendai virus strain Tianjin (UV-Tianjin) has been proved to have antitumor effects in many kinds of tumor cells. Here, we investigated the anticancer properties of UV-Tianjin on human osteosarcoma HOS cells and the underlying molecular mechanism. Apoptosis, intracellular reactive oxygen species (ROS) levels and mitochondrial membrane potential were determined by flow cytometry analysis. The expression levels of apoptosis-related proteins were tested by western blotting. The results showed that UV-Tianjin concentration-dependently induced apoptosis in HOS cells. UV-Tianjin-induced apoptosis was mediated by the mitochondrial pathway, which was confirmed by mitochondrial dysfunction, downregulation of B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-xL (Bcl-xL) and myeloid cell leukemia-1 (Mcl-1), upregulation of B-cell lymphoma 2 associated X protein (Bax) and Bcl-2 Homologous Antagonist/Killer (Bak), as well as the cleavage of caspase-9 and -3. Further analysis showed that UV-Tianjin augmented the phosphorylation of c-Jun N-terminal kinase, the extracellular-regulated kinase and p38, the major components of mitogen-activated protein kinase (MAPK) pathways, as well as the generation of ROS. Moreover, UV-Tianjin-induced apoptosis was remarkably attenuated by MAPK inhibitors and ROS inhibitor. Taken together, our results indicated that UV-Tianjin exerts antitumor effects by inducing mitochondria-dependent apoptosis involving ROS generation and MAPK pathway in human osteosarcoma HOS cells.
Insights
Ultraviolet-inactivated Sendai virus strain Tianjin (UV-Tianjin) effectively induces apoptosis in human osteosarcoma cells. This antitumor effect involves mitochondrial dysfunction, reactive oxygen species generation, and the MAPK pathway.
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- Ultraviolet-inactivated Sendai virus strain Tianjin (UV-Tianjin) exhibits known antitumor properties.
- Osteosarcoma remains a significant challenge in orthopedic oncology.
Purpose of the Study:
- To investigate the anticancer effects of UV-Tianjin on human osteosarcoma HOS cells.
- To elucidate the molecular mechanisms underlying UV-Tianjin's antitumor activity.
Main Methods:
- Flow cytometry was used to assess apoptosis, intracellular reactive oxygen species (ROS) levels, and mitochondrial membrane potential.
- Western blotting analyzed the expression of apoptosis-related proteins.
- Mitogen-activated protein kinase (MAPK) inhibitors and ROS inhibitors were employed.
Main Results:
- UV-Tianjin induced apoptosis in HOS cells in a dose-dependent manner.
- Apoptosis was mediated by the mitochondrial pathway, evidenced by mitochondrial dysfunction and altered expression of Bcl-2 family proteins (Bcl-2, Bcl-xL, Mcl-1, Bax, Bak).
- UV-Tianjin treatment increased ROS generation and activated MAPK pathways (JNK, ERK, p38), which were crucial for apoptosis induction.
Conclusions:
- UV-Tianjin exerts antitumor effects on human osteosarcoma cells by triggering mitochondria-dependent apoptosis.
- The mechanism involves ROS generation and activation of the MAPK signaling pathway.
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