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Monitoring Dynamic Changes In Mitochondrial Calcium Levels During Apoptosis Using A Genetically Encoded Calcium Sensor
Published on: April 1, 2011
Activin A induces apoptosis of mouse myeloma cells via the mitochondrial pathway
Yuanyi Zhang1, Yan Qi1, Yang Zhao1
1Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China.
Abstract:
Activin A is a pleiotropic cytokine belonging to the transforming growth factor β superfamily. Abnormal expression of activin A is associated with tumorigenesis. Multiple myeloma is characterized by the development of osteolytic disease, which ultimately leads to cachexia. However, the involvement of activin A in myeloma cell viability and apoptosis remains to be fully elucidated. For this purpose, mouse myeloma NS-1 cells were treated with activin A, and subsequently subjected to 5-bromo-2'-deoxyuridine analysis, Hoechst 33342 staining, flow cytometry and western blot analysis. The results revealed that activin A significantly suppressed NS-1 cell viability, and induced NS-1 cell apoptosis. In addition, activin A-induced promotion of NS-1 cell apoptosis was accompanied by upregulated expression of BCL2 associated X, apoptosis regulator (Bax), but downregulated expression of B cell lymphoma-2 (Bcl-2), resulting in an increase of the Bax/Bcl-2 ratio. Furthermore, cytochrome c and caspase-3 protein expression also increased following treatment with activin A. These data suggest that activin A induces apoptosis in mouse myeloma NS-1 cells via the mitochondrial pathway, providing a novel insight into multiple myeloma treatment.
Insights
Activin A significantly reduces multiple myeloma cell viability and triggers apoptosis. This cytokine impacts the Bax/Bcl-2 ratio and mitochondrial pathway proteins, offering potential new avenues for myeloma treatment.
Area of Science:
- Cell Biology
- Molecular Biology
- Oncology
Background:
- Activin A, a TGF-β superfamily cytokine, is implicated in tumorigenesis.
- Multiple myeloma involves osteolytic lesions and cachexia, but activin A's role in myeloma cell apoptosis is unclear.
Purpose of the Study:
- To investigate the effect of activin A on multiple myeloma cell viability and apoptosis.
- To elucidate the molecular mechanisms underlying activin A-induced apoptosis in myeloma cells.
Main Methods:
- Treatment of mouse myeloma NS-1 cells with activin A.
- Analysis using 5-bromo-2'-deoxyuridine assay, Hoechst 33342 staining, flow cytometry, and western blot.
Main Results:
- Activin A suppressed NS-1 cell viability and induced apoptosis.
- Apoptosis involved upregulation of Bax and downregulation of Bcl-2, increasing the Bax/Bcl-2 ratio.
- Activin A increased cytochrome c and caspase-3 protein expression.
Conclusions:
- Activin A induces apoptosis in mouse myeloma NS-1 cells through the mitochondrial pathway.
- These findings offer novel insights into potential therapeutic strategies for multiple myeloma.
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