Differential roles of 2, 6, and 8 carbon ceramides on the modulation of gap junctional communication and apoptosis during carcinogenesis.
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.
Upham
Brad L
BL
Department of Pediatrics and Human Development, Michigan State University, 243 Food Safety and Toxicology, East Lansing, MI 48824, USA. upham@msu.edu
Koski
Tyler R
TR
Rummel
Alisa M
AM
Wilson
Melinda R
MR
Horvath
Anelia
A
Trosko
James E
JE
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002273:Carcinogens / Q000737:chemistry / Q000633:toxicity; D002450:Cell Communication / Q000187:drug effects*; D002460:Cell Line / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002518:Ceramides / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects; D017629:Gap Junctions / Q000187:drug effects*; D008099:Liver / Q000166:cytology; D015394:Molecular Structure; D051381:Rats; D011916:Rats, Inbred F344; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D013329:Structure-Activity Relationship
D002273:Carcinogens; D002518:Ceramides; C064769:N-acetylsphingosine; C101954:N-caproylsphingosine; D013110:Sphingosine