Upregulation of connexin 43 by retinoids but not by non-provitamin A carotenoids requires RARs

Nutr Cancer. 2005;52(1):105-13. doi: 10.1207/s15327914nc5201_13.

Abstract

Expression of connexin 43 (Cx43) is correlated with reduced indexes of neoplasia and is upregulated by cancer-preventive retinoids and carotenoids in nontransformed human and murine fibroblasts and keratinocytes. The molecular mechanism of upregulation, however, is poorly understood. Three retinoic acid receptor (RAR) antagonists (Ro 41-5253, BMS453, and BMS493) were capable of suppressing retinoid-induced Cx43 protein expression in 10T1/2 cells. However, Ro 41-5253 did not suppress protein expression by the non-provitamin A carotenoids astaxanthin or lycopene. In contrast, Cx43 induction by astaxanthin but not by a RAR-specific retinoid was inhibited by GW9662, an antagonist of peroxisome proliferator activated receptor-gamma activation. Simultaneous treatment with the maximally effective concentration of a retinoid and with beta-carotene or the non-provitamin A carotenoid astaxanthin resulted in supraadditive upregulation of Cx43 expression, again indicating separate mechanisms of gene regulation by these two cancer preventive agents.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anticarcinogenic Agents / pharmacology
  • Antioxidants / pharmacology*
  • Benzoates / pharmacology
  • Carotenoids / pharmacology*
  • Cell Line
  • Connexin 43 / metabolism*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Mice
  • Neoplasms / prevention & control
  • PPAR gamma / antagonists & inhibitors
  • PPAR gamma / metabolism
  • Receptors, Retinoic Acid / antagonists & inhibitors
  • Receptors, Retinoic Acid / metabolism*
  • Retinoids / pharmacology*
  • Up-Regulation / drug effects*
  • Xanthophylls
  • beta Carotene / analogs & derivatives
  • beta Carotene / pharmacology

Substances

  • Anticarcinogenic Agents
  • Antioxidants
  • Benzoates
  • Connexin 43
  • PPAR gamma
  • Receptors, Retinoic Acid
  • Retinoids
  • Xanthophylls
  • beta Carotene
  • Carotenoids
  • 4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid
  • astaxanthine