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Journal of Neuro-Oncology
Published in: Journal of Neuro-Oncology 2/2008

01-04-2008 | lab investigation-human/animal tissue

Vincristine and lomustine induce apoptosis and p21WAF1 up-regulation in medulloblastoma and normal human epithelial and fibroblast cells

Authors: Zakia Shinwari, Pulicat S. Manogaran, Salman A. Alrokayan, Khaled A. Al-Hussein, Abdelilah Aboussekhra

Published in: Journal of Neuro-Oncology | Issue 2/2008

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Abstract

Medulloblastomas arise in the cerebellum and are the most common pediatric primary malignant brain tumors. Currently, medulloblastoma patients are best treated with surgical removal of the tumor, adjuvant radiation therapy and chemotherapy. The chemotherapeutic agents that showed efficiency against medulloblastomas include lomustine and vincristine. However, the effects of these drugs on medulloblastomas as well as on other cell types is still not well defined. In the present report we present evidence that the cytotoxic effect of these drugs is not specific for medulloblastoma cells but includes also normal fibroblast and epithelial cells. We have also shown that vincristine and lomustine trigger apoptosis in all these cells through the mitochondrial pathway via decrease in the level of the anti-apoptosis proteins Bcl-2 and Bcl-xl, respectively. Intriguingly, the proportion of apoptotic cells induced in medulloblastoma and normal epithelial and fibroblastic cells was similar. In addition, vincristine induced low proportion of necrosis in medulloblastoma and normal fibroblast cells. Interestingly, while vincristine induced cell cycle delay in G2/M phase in normal as well as medulloblastoma cells, lomustine effect on the cell cycle was specific for medulloblastoma cells. Furthermore, we have shown that vincristine and lomustine up-regulated p21 protein level in a p53-independent manner. These results shed more light on the biological effects of vincristine and lomustine and show that lomustine is a more specific and potent anti-medulloblastoma agent.
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Metadata
Title
Vincristine and lomustine induce apoptosis and p21WAF1 up-regulation in medulloblastoma and normal human epithelial and fibroblast cells
Authors
Zakia Shinwari
Pulicat S. Manogaran
Salman A. Alrokayan
Khaled A. Al-Hussein
Abdelilah Aboussekhra
Publication date
01-04-2008
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 2/2008
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-007-9502-4

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