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Cisplatin-induced cell death in human glioma
M Matsumoto1, T Tsuchida, K Kawamoto
1KANSAI MED UNIV,DEPT NEUROSURG,MORIGUCHI,OSAKA 570,JAPAN.
Abstract:
It has been reported that apoptosis is a predominant mode of death of tumor cells treated with cisplatin. It is unclear, however, whether cells of all tumor types, without exception, respond to cisplatin by apoptosis. In particular, the mode of death of glioma cells has not been investigated. In the present study human glioma U251 MG cells were treated in vitro with 1 or 10 mu g/ml cisplatin and their mode of death was analyzed by flow cytometry, DNA gel electrophoresis, examination of cell morphology following their staining with Giemsa and electron microscopy. The absence of a sub-G1 peak on the DNA content frequency histogram, the absence of DNA laddering on agarose gels, no nuclear fragmentation but distinct mitochondrial swelling were the features of U251 MG cells dying in the presence of cisplatin. Since these features are characteristic of necrosis rather than apoptosis the data indicate that the mode of cell death of some tumors treated with cisplatin may be necrosis.
Insights
Cisplatin treatment can induce cell death in tumor cells. However, this study found that human glioma cells treated with cisplatin undergo necrosis, not apoptosis, indicating varied tumor responses to chemotherapy.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Apoptosis is a common cell death pathway for tumor cells treated with cisplatin.
- The specific cell death mechanisms in glioma cells exposed to cisplatin remain uninvestigated.
Purpose of the Study:
- To investigate the mode of cell death in human glioma U251 MG cells treated with cisplatin.
- To determine if glioma cells undergo apoptosis or another cell death pathway in response to cisplatin.
Main Methods:
- In vitro treatment of human glioma U251 MG cells with cisplatin (1 or 10 μg/ml).
- Analysis of cell death using flow cytometry, DNA gel electrophoresis, Giemsa staining for morphology, and electron microscopy.
Main Results:
- Absence of a sub-G1 peak in DNA content histograms, indicating no apoptotic DNA fragmentation.
- No DNA laddering observed on agarose gels.
- Distinct mitochondrial swelling and lack of nuclear fragmentation observed, characteristic of necrosis.
Conclusions:
- Human glioma U251 MG cells treated with cisplatin exhibit features of necrosis, not apoptosis.
- This suggests that not all tumor types respond to cisplatin via apoptosis, with necrosis being a possible alternative pathway.