Abstract
Increasing the susceptibility of tumor cells to apoptotic cell death following chemotherapy is of importance to the outcome of cancer treatment. Although the tumor suppressor gene p53 is required for efficient induction of apoptosis by chemotherapeutic agents, it is not the only apoptosis mediator gene. The molecular mechanisms mediating apoptosis following chemotherapy via p53-dependent or p53-independent pathways remain unclear. We show here that cis-diamminedichloroplatinum (cis-platin) induces the expression of interleukin-1β-converting enzyme (ICE), a mammalian homologue of the Caenorhabiditis elegans cell death gene ced-3, in murine and human malignant glioma cells during apoptosis regardless of their p53 status. Furthermore, overexpression of the murine ICE gene induces apoptosis in these tumor cells. The apoptosis induced by cisplatin treatment or murine ICE overexpression can be suppressed by the tetrapeptide ICE inhibitor Ac-YVAD-CMK or the apoptosis inhibitors bcl-2 or bcl-2-related bcl-Xl gene. These findings suggest that ICE may mediate apoptosis induced by chemotherapy, and its induction could represent a novel approach for the effective treatment of malignant glioma.
Footnotes
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↵1 This study was supported in part by Cleveland Clinic Foundation Research Fund Grant 4941 and the John Gagliarducci Fund.
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↵2 To whom requests for reprints should be addressed, at Department of Neurosurgery/S/180, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195. Phone: (216) 445-4684; Fax: (216) 444-9170.
- Received July 17, 1995.
- Accepted October 26, 1995.
- ©1995 American Association for Cancer Research.
Volume 55, Issue 24
