Effects of n-6 and n-3 polyunsaturated fatty acids on gap junctional intercellular communication during spontaneous differentiation of the human colon adenocarcinoma cell line Caco-2.
Gap junctional intercellular communication (GJIC), which modulates cell growth and differentiation, may play an important role in tumor growth. Cancer cells have dysfunctional GJIC, but it is not known whether GJIC is mechanistically involved in the carcinogenic and anti-carcinogenic effects of n-6 and n-3 polyunsaturated fatty acids (PUFAs) on colon tumor cells. Caco-2 cells were used as an in vitro model to study the effects of PUFAs on differentiated as well as undifferentiated human colon cells. The GJIC capacity of this cell line increased during spontaneous differentiation. However, no differential effects between n-6 and n-3 PUFAs on GJIC were observed. Short-term incubation with linoleic acid (18:2n-6), alpha-linolenic acid (18:3n-3), arachidonic acid (AA, 20:4n-6), and eicosapentaenoic acid (EPA, 20:5n-3) did not influence GJIC, while long-term incubation (> 10 days) with linoleic acid and alpha-linolenic acid inhibited GJIC of these colon cells. Long-chain metabolites such as AA and EPA were not formed after incubation with linoleic acid and alpha-linolenic acid, thus excluding the involvement of prostaglandins in the observed effects. Although the exact mechanism of GJIC inhibition is unclear, cytotoxicity probably mediated by lipid peroxidation products seems to be related, because incubation with more PUFAs (AA and EPA) completely abolished GJIC.
Dommels
Yvonne E M
YE
Division of Toxicology, Wageningen University, Wageningen, The Netherlands. yvonne.dommels@algemeen.tox.wau.nl
Alink
Gerrit M
GM
Linssen
Jozef P H
JP
van Ommen
Ben
B
D000230:Adenocarcinoma / Q000473:pathology*; D018938:Caco-2 Cells; D002450:Cell Communication / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D017629:Gap Junctions / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007365:Intercellular Junctions / Q000187:drug effects* / Q000502:physiology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D014407:Tumor Cells, Cultured
D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D007770:L-Lactate Dehydrogenase