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Nitric oxide-mediated apoptosis of K-1735 melanoma cells is associated with downregulation of Bcl-2.
- Source :
-
Oncogene . 8/14/97, Vol. 15 Issue 7, p771. 9p. 1 Black and White Photograph, 5 Graphs. - Publication Year :
- 1997
-
Abstract
- Recent studies have shown that the treatment of nonmetastatic K-1735 murine melanoma cells with cytokines induces the production of nitric oxide (NO) and hence cell death. The purpose of this study was to determine the mechanism of this cytokine-induced NO-mediated apoptosis. Incubation of nonmetastatic K-1735 cells with interleukin-1 alpha (IL-1α) and interferon-gamma (IFN-γ) induced high NO production, Bcl-2 downregulation, and apoptotic cell death. In contrast, incubation of metastatic K-1735 cells with IL-1α and IFN-γ did not induce significant production of NO, downregulation of Bcl-2, or cell death. The exposure to exogenous NO derived from the NO donors, sodium nitroprusside (SNP), or GEA5024 produced a dose-dependent apoptotic cell death in both the metastatic and nonmetastatic K-1735 cells, which was associated with downregulation of Bcl-2 at the mRNA level and, to a lesser extent, at the protein level. Nonmetastatic and metastatic K-1735 cells transfected with the Bcl-2 gene were more resistant to apoptosis mediated by both endogenous and exogenous NO. Subsequent to intravenous injection, the tumor cells transfected with the Bcl-2 gene had an increased survival rate in the lungs of nude mice and produced a higher number of experimental lung metastases. These data suggest that NO-induced apoptosis in K-1735 melanoma cells is associated with downregulation of Bcl-2. [ABSTRACT FROM AUTHOR]
- Subjects :
- *NITRIC oxide
*APOPTOSIS
*MELANOMA
*CANCER cells
Subjects
Details
- Language :
- English
- ISSN :
- 09509232
- Volume :
- 15
- Issue :
- 7
- Database :
- Academic Search Index
- Journal :
- Oncogene
- Publication Type :
- Academic Journal
- Accession number :
- 8917052
- Full Text :
- https://doi.org/10.1038/sj.onc.1201239