TAC-101, a novel retinobenzoic-acid derivative, enhances gap junctional intercellular communication among renal epithelial cells treated with renal carcinogens

Anticancer Res. 2001 Nov-Dec;21(6A):4025-30.

Abstract

[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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticarcinogenic Agents / pharmacology*
  • Benzoates / pharmacology*
  • Blotting, Western
  • Bromides / pharmacology
  • Carcinogens / pharmacology*
  • Cell Communication / drug effects*
  • Cell Communication / physiology
  • Cell Division / drug effects
  • Cell Membrane Permeability / drug effects
  • Connexin 43 / metabolism
  • Dimethylnitrosamine / pharmacology
  • Dogs
  • Drug Interactions
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Fluorescent Antibody Technique
  • Gap Junctions / drug effects*
  • Gap Junctions / metabolism
  • Gap Junctions / physiology
  • Kidney / cytology*
  • Kidney / drug effects*
  • Kidney Neoplasms / chemically induced
  • Kidney Neoplasms / prevention & control
  • Phosphorylation
  • Potassium Compounds / pharmacology
  • Trimethylsilyl Compounds / pharmacology*
  • Up-Regulation / drug effects

Substances

  • Anticarcinogenic Agents
  • Benzoates
  • Bromides
  • Carcinogens
  • Connexin 43
  • Potassium Compounds
  • TAC 101
  • Trimethylsilyl Compounds
  • Dimethylnitrosamine
  • potassium bromide