Differential responses of human neuroblastoma and glioblastoma to apoptosis
S Bursztajn1, J J Feng, A Nanda
1Department of Pathology, Dartmouth Medical College and VA Medical Center, 215 North Main St. Research Building #44, White River Junction, VT 05009, USA. sherry.bursztajn@darmouth.edu
Abstract:
Staurosporine, a protein kinase and etoposide, a topoisomerase II inhibitor, are known to enhance apoptosis. The differential effects of these agents on T98G glioblastoma and SK-N-SH neuroblastoma, cell lines both derived from human tumors, have not been determined. We assessed cellular viability, DNA fragmentation and laddering, chromatin condensation, and Poly(ADP-ribose) polymerase (PARP) cleavage induced by these agents at a series of concentrations and times. In addition, to gain an understanding of the mechanism by which these agents work, we measured Protein Kinase C (PKC) activity. Staurosporine induced significant alterations in all apoptotic parameters tested in both cell lines. Etoposide induced apoptotic alterations similar to those caused by staurosporine in neuroblastoma but produced no detectable apoptotic changes in glioblastoma cells. Etoposide induced membrane but not cytosolic PKC activity in neuroblastoma but had no effect on PKC activity in glioblastoma. Our results show that the induction of apoptosis is cell type dependent. PKC activity appears to be crucial in the initiation of apoptosis.
Insights
Staurosporine and etoposide induce apoptosis differently in human glioblastoma and neuroblastoma cells. Protein Kinase C (PKC) activity is crucial for apoptosis initiation, showing cell-type-dependent responses to these agents.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Apoptosis, or programmed cell death, is a critical cellular process.
- Staurosporine (a protein kinase inhibitor) and etoposide (a topoisomerase II inhibitor) are known apoptosis enhancers.
- Differential effects of these agents on human glioblastoma (T98G) and neuroblastoma (SK-N-SH) cells are not well understood.
Purpose of the Study:
- To investigate the differential effects of staurosporine and etoposide on apoptosis in T98G glioblastoma and SK-N-SH neuroblastoma cell lines.
- To elucidate the role of Protein Kinase C (PKC) activity in the apoptotic mechanisms of these agents.
Main Methods:
- Assessment of cellular viability, DNA fragmentation, chromatin condensation, and Poly(ADP-ribose) polymerase (PARP) cleavage.
- Measurement of Protein Kinase C (PKC) activity in response to staurosporine and etoposide treatment.
- Comparative analysis across different concentrations and time points in both cell lines.
Main Results:
- Staurosporine induced significant apoptosis in both glioblastoma and neuroblastoma cells.
- Etoposide induced apoptosis in neuroblastoma cells but not in glioblastoma cells.
- Etoposide modulated PKC activity in neuroblastoma but not glioblastoma cells, suggesting cell-type-specific mechanisms.
Conclusions:
- Apoptosis induction by etoposide is dependent on cell type.
- PKC activity plays a crucial role in the initiation of apoptosis.
- These findings highlight the importance of cell context in drug-induced apoptosis.
