Lambda-carrageenan-induced inhibition of gap-junctional intercellular communication in rat liver epithelial cells.
lambda-Carrageenan, a food additive extracted from red seaweed, is widely used as an emulsifier, stabilizer, or thickener. Previously, it has been shown that carrageenan could play a role in carcinogenesis. However, the mechanism by which it might influence the multimechanism, multistep process of carcinogenesis is not known. Gap-junctional intercellular communication (GJIC) has been associated with maintaining homeostatic regulation of cell proliferation and differentiation. Most cancer cells have dysfunctional GJIC, and many tumor-promoting chemicals, growth factors, and oncogenes can downregulate GJIC. The experiments in this study were designed to test the hypothesis that carrageenan might function as a tumor-promoting chemical by inhibiting GJIC. To test this hypothesis, nontumorigenic rat liver epithelial cells were exposed to carrageenan, and GJIC was measured. Western blot analysis and immunofluorescent staining were used to monitor the phosphorylation and localization of connexin 43. The data revealed inhibition of GJIC by carrageenan similar to that by the well-documented tumor promoter phorbol ester. However, the phosphorylation and localization of connexin 43 were not altered. Although the mechanism by which carrageenan inhibits GJIC is unknown, carrageenan's influence on the carcinogenic process might be via its ability to be a tumor promoter.
Suzuki
J
J
Department of Pediatrics and Human Development, Michigan State University, East Lansing 48824, USA.
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H K
HK
Upham
B L
BL
Chang
C C
CC
Trosko
J E
JE
D000818:Animals; D000911:Antibodies, Monoclonal; D002351:Carrageenan / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018031:Connexin 43 / Q000032:analysis / Q000378:metabolism; D004847:Epithelial Cells / Q000737:chemistry / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D017629:Gap Junctions / Q000737:chemistry / Q000187:drug effects*; D006651:Histocytochemistry; D008099:Liver / Q000737:chemistry / Q000648:ultrastructure*; D010766:Phosphorylation; D051381:Rats
D000911:Antibodies, Monoclonal; D018031:Connexin 43; D002351:Carrageenan