TAC-101, a novel retinobenzoic-acid derivative, enhances gap junctional intercellular communication among renal epithelial cells treated with renal carcinogens.
[4-3,5-Bis(trimethylsilyl)benzamido] benzoic acido] (TAC-101), which exhibits an anti-tumor effect, can bind to retinoic acid receptors (RARs). It has retinoid-like properties, such as chemopreventive action against cancer cells. The up-regulation of connexin (Cx) expression by retinoids is well known in various epithelial cells. In this study, we investigated whether TAC-101 up-regulates gap junctional intercellular communication (GJIC) in renal epithelial cells exposed to the renal carcinogens. Madin Darby canine kidney (MDCK) cells were incubated with TAC-101 for 3 days, then briefly exposed to renal carcinogens potassium bromate (KBrO3) or dimethylnitrosamine (DMN). TAC-101 increased the expression of connexin 43 protein without affecting Cx43 phosphorylation and prevented inadequate Cx43 localisation caused by KBrO3 or DMN. Consequently, TAC-101 prevented the disruption of GJIC in MDCK cells. These data suggested that TAC-101 enhanced GJIC by up-regulating Cx43 expression and that TAC-101 might be useful for the prevention of renal cell carcinoma.
Miyaguchi
T
T
Department of Urology, Nagasaki University School of Medicine, Japan.
Nomata
K
K
Noguchi
M
M
Watanabe
J
J
Satoh
H
H
Kanetake
H
H
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D015153:Blotting, Western; D001965:Bromides / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology*; D002450:Cell Communication / Q000187:drug effects* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D018031:Connexin 43 / Q000378:metabolism; D004128:Dimethylnitrosamine / Q000494:pharmacology; D004285:Dogs; D004347:Drug Interactions; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D017629:Gap Junctions / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D007668:Kidney / Q000166:cytology* / Q000187:drug effects*; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000517:prevention & control; D010766:Phosphorylation; D017680:Potassium Compounds / Q000494:pharmacology; D014297:Trimethylsilyl Compounds / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D016588:Anticarcinogenic Agents; D001565:Benzoates; D001965:Bromides; D002273:Carcinogens; D018031:Connexin 43; D017680:Potassium Compounds; C112689:TAC 101; D014297:Trimethylsilyl Compounds; D004128:Dimethylnitrosamine; C039004:potassium bromide