Journal
JOURNAL OF PROTEOME RESEARCH
Volume 8, Issue 10, Pages 4810-4822Publisher
AMER CHEMICAL SOC
DOI: 10.1021/pr9005316
Keywords
2D-DIGE; cancer cells; ceramide; Btf; apoptosis
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Funding
- Centre Anti-Cancereux (Liege, Belgium)
- FNRS
- Fonds Leon Fredericq (Liege, Belgium)
- Televie
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Ceramides are central molecules in sphingolipid metabolism. They are involved in the regulation of cancer-cell growth, differentiation, senescence and apoptosis. To better understand how these secondary messengers induce their biological effects, adenocarcinoma cells (HCT116) were treated with exogenous long-chain ceramides (C16-ceramide) in order to mimic endogenous sphingolipids. This treatment induced a decrease of cell viability partly due to apoptosis as shown by PARP cleavage and a decrease of pro-caspase 3. Two-dimensional differential in-gel electrophoresis (2D-DIGE) revealed the differential expression of 51 proteins in response to C16-ceramide. These proteins are notably involved in cell proliferation, apoptosis, protein transport and transcriptional regulation. Among them, the cell death-promoting factor Btf was found to be implicated in the apoptotic signal triggered by ceramide. In adenocarcinoma cells, Btf regulates apoptosis related proteins such as Mdm2, p53, BAX and (p)Bcl-2 and thus plays an important role in the ceramide mediated cell death. These findings bring new insight into the proapoptotic ceramide-dependent signaling pathway.
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