Indole-3-carbinol prevents H(2)O(2)-induced inhibition of gap junctional intercellular communication by inactivation of PKB/Akt.
Indole-3-carbinol (I3C) is a phytochemical found in cruciferous vegetables and possesses a variety of biological and biochemical effects. Despite a wealth of data about the chemopreventive properties of I3C, its effects on gap junctional intercellular communication (GJIC), which is associated with the promotion and progression phases of the multi-stage process of carcinogenesis, has not been studied. In this study, we examined the ability of I3C to prevent H(2)O(2)-induced inhibition of GJIC in WB-F344 rat liver epithelial cells (WB cells). The cells were preincubated with I3C for 48 hr, and then treated with 1 mM H(2)O(2) for 1 hr. We found that I3C could prevent the H(2)O(2)-induced inhibition of GJIC through prevention of the phosphorylated state of gap junction protein connexin 43 (Cx43) phosphorylation. Prevention of GJIC by I3C was dependent upon inactivation of Akt, but not MAPK, although inhibition of GJIC by H(2)O(2) leads to activation of both. Similar to I3C, modulation of Akt activation through the phosphoinositide-3 kinase inhibitor, LY294002, could also prevent H(2)O(2)-induced inhibition of GJIC and phosphorylation of Cx43. Our results suggest that I3C might exert its dietary chemopreventive effects by interfering with the Akt signaling pathway, which appears to be linked to modulating GJIC, a cellular mechanisms regulating cell proliferation, differentiation and apoptosis.
Hwang
Jae-Woong
JW
Laboratory of Stem Cell and Tumor Biology, Department of Veterinary Public Health, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
Jung
Ji-Won
JW
Lee
Yong-Soon
YS
Kang
Kyung-Sun
KS
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002450:Cell Communication / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D018031:Connexin 43 / Q000378:metabolism; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D017629:Gap Junctions / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D009025:Morpholines / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
D016588:Anticarcinogenic Agents; D002867:Chromones; D018031:Connexin 43; D004791:Enzyme Inhibitors; D007211:Indoles; D009025:Morpholines; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D006861:Hydrogen Peroxide; C016517:indole-3-carbinol; D051057:Proto-Oncogene Proteins c-akt