Abstract
The inhibition of apoptosis and gap junctional intercellular communication (GJIC) has been implicated in tumor promotion. Ionizing radiation and oxidative toxicants activate sphingomyelinases resulting in the release of ceramides that control cell proliferation and apoptosis. A rat liver epithelial cell line treated with ceramides containing a 6 (C6) or 8 (C8) carbon acyl-group were potent inhibitors of GJIC and apoptosis, whereas a C2-ceramide was only a weak inhibitor of GJIC and strong inducer of apoptosis. Apoptosis induced by either serum deprivation or C2-ceramide was inhibited by the GJIC inhibitory C8-ceramide. In conclusion, these results suggest that a chronic release of ceramides with acyl groups larger than C6 might act as tumor promoters.
Original language | English (US) |
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Pages (from-to) | 27-34 |
Number of pages | 8 |
Journal | Cancer Letters |
Volume | 191 |
Issue number | 1 |
DOIs | |
State | Published - Feb 28 2003 |
Funding
We thank Mr Jacob Scott for his technical assistance in the Western blot analysis of Cx43. This research was supported by the National Institute of Environmental Health Science Superfund (grant #P42 ES04911-07) to JET.
Keywords
- Apoptosis
- Ceramide
- Gap junctional intercellular communication
- Signal transduction
- Tumor promotion
ASJC Scopus subject areas
- Oncology
- Cancer Research