Abstract
The survival of patients with malignant gliomas is still unsatisfactory despite multimodality treatment, therefore new therapeutic strategies are required. Tumor necrosis factor apoptosis related ligand (TRAIL/ Apo2L), a member of the tumor necrosis factor superfamily, may induce apoptotic cell death in several tumors, but not in normal cells, upon binding with specific receptors. In the present study, the expression and function of TRAIL receptors (TRAIL-R1/DR4 and TRAIL-R2/DR5) has been investigated in five human glioma cell lines (U87, U138, U373, A172, SW1783) in ex vivo tumors and in primary cultures obtained from the tumors. Our data show that gliomas preferentially express TRAIL R2 and that treatment with topotecan, a topoisomerase I inhibitor, significantly up-regulates its expression as detected by flow cytometry and western blotting. Moreover, in most cases, treatment with topotecan resulted in an increased sensitivity to TRAIL-dependent apoptosis, although cyclohexymide had to be added to induce apoptosis. On glioma cell lines, the effects of irradiation on TRAIL receptors were also analysed. In our experimental conditions, irradiation with 2 Gy had a modest additive effect on TRAIL-dependent apoptosis and was not able to modulate TRAIL receptor expression.
| Original language | English |
|---|---|
| Pages (from-to) | 19-25 |
| Number of pages | 7 |
| Journal | Journal of Neuro-Oncology |
| Volume | 71 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 2005 |
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Keywords
- Apoptosis
- Glioma
- Radiation
- Topotecan
- TRAIL
ASJC Scopus subject areas
- Cancer Research
- Clinical Neurology
- Oncology
- Neuroscience(all)
Cite this
In vitro effects of topotecan and ionizing radiation on TRAIL/ Apo2L-mediated apoptosis in malignant glioma. / Ciusani, Emilio; Croci, Danilo; Gelati, Maurizio; Calatozzolo, Chiara; Sciacca, Francesca; Fumagalli, Luisa; Balzarotti, Marco; Fariselli, Laura; Boiardi, Amerigo; Salmaggi, Andrea.
In: Journal of Neuro-Oncology, Vol. 71, No. 1, 01.2005, p. 19-25.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - In vitro effects of topotecan and ionizing radiation on TRAIL/ Apo2L-mediated apoptosis in malignant glioma
AU - Ciusani, Emilio
AU - Croci, Danilo
AU - Gelati, Maurizio
AU - Calatozzolo, Chiara
AU - Sciacca, Francesca
AU - Fumagalli, Luisa
AU - Balzarotti, Marco
AU - Fariselli, Laura
AU - Boiardi, Amerigo
AU - Salmaggi, Andrea
PY - 2005/1
Y1 - 2005/1
N2 - The survival of patients with malignant gliomas is still unsatisfactory despite multimodality treatment, therefore new therapeutic strategies are required. Tumor necrosis factor apoptosis related ligand (TRAIL/ Apo2L), a member of the tumor necrosis factor superfamily, may induce apoptotic cell death in several tumors, but not in normal cells, upon binding with specific receptors. In the present study, the expression and function of TRAIL receptors (TRAIL-R1/DR4 and TRAIL-R2/DR5) has been investigated in five human glioma cell lines (U87, U138, U373, A172, SW1783) in ex vivo tumors and in primary cultures obtained from the tumors. Our data show that gliomas preferentially express TRAIL R2 and that treatment with topotecan, a topoisomerase I inhibitor, significantly up-regulates its expression as detected by flow cytometry and western blotting. Moreover, in most cases, treatment with topotecan resulted in an increased sensitivity to TRAIL-dependent apoptosis, although cyclohexymide had to be added to induce apoptosis. On glioma cell lines, the effects of irradiation on TRAIL receptors were also analysed. In our experimental conditions, irradiation with 2 Gy had a modest additive effect on TRAIL-dependent apoptosis and was not able to modulate TRAIL receptor expression.
AB - The survival of patients with malignant gliomas is still unsatisfactory despite multimodality treatment, therefore new therapeutic strategies are required. Tumor necrosis factor apoptosis related ligand (TRAIL/ Apo2L), a member of the tumor necrosis factor superfamily, may induce apoptotic cell death in several tumors, but not in normal cells, upon binding with specific receptors. In the present study, the expression and function of TRAIL receptors (TRAIL-R1/DR4 and TRAIL-R2/DR5) has been investigated in five human glioma cell lines (U87, U138, U373, A172, SW1783) in ex vivo tumors and in primary cultures obtained from the tumors. Our data show that gliomas preferentially express TRAIL R2 and that treatment with topotecan, a topoisomerase I inhibitor, significantly up-regulates its expression as detected by flow cytometry and western blotting. Moreover, in most cases, treatment with topotecan resulted in an increased sensitivity to TRAIL-dependent apoptosis, although cyclohexymide had to be added to induce apoptosis. On glioma cell lines, the effects of irradiation on TRAIL receptors were also analysed. In our experimental conditions, irradiation with 2 Gy had a modest additive effect on TRAIL-dependent apoptosis and was not able to modulate TRAIL receptor expression.
KW - Apoptosis
KW - Glioma
KW - Radiation
KW - Topotecan
KW - TRAIL
UR - http://www.scopus.com/inward/record.url?scp=14044267654&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=14044267654&partnerID=8YFLogxK
U2 - 10.1007/s11060-004-9180-4
DO - 10.1007/s11060-004-9180-4
M3 - Article
VL - 71
SP - 19
EP - 25
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
SN - 0167-594X
IS - 1
ER -