Peroxisome proliferator-activated receptor gamma-dependent activity of indole ring-substituted 1,1-bis(3'-indolyl)-1-(p-biphenyl)methanes in cancer cells.
Cancer Chemother Pharmacol
; 66(1): 141-50, 2010 May.
Article
em En
| MEDLINE
| ID: mdl-19823826
ABSTRACT
PURPOSE:
1,1-Bis(3-indolyl)-1-(p-substituted phenyl)methanes (C-DIMs) substituted in the phenyl ring with a para-, t-butyl, trifluoromethyl (DIM-C-pPhCF(3)) or phenyl (DIM-C-pPhC(6)H(5)) group activate peroxisome proliferator-activated receptor gamma (PPARgamma) in several cancer cell lines, and DIM-C-pPhCF(3) also activates the orphan receptor Nur77. In this study, we have examined the effects of 5,5'-dihydroxy, 5,5'-dimethyl, 5,5'-dibromo, 5,5'-dinitro and 5,5'-dimethoxyindole ring-substituted analogs of DIM-C-pPhC(6)H(5) on their activity as PPARgamma agonists.METHODS:
Various substituted C-DIM analogs were used to investigate their growth-inhibitory activities and activation of PPARgamma-mediated transactivation in colon and pancreatic cancer cells. Their structure-dependent induction of putative PPARgamma-responsive genes/proteins including p21, KLF-4 and caveolin1 were also determined by Western and Northern blot analysis.RESULTS:
Introduction of the 5,5'-dihydroxy and 5,5'-dimethyl substituents enhanced activation of PPARgamma in colon and pancreatic cancer cells. However, activation of p21 in Panc28 pancreatic cancer cells and induction of caveolin-1 and KLF4 in colon cancer cells by the C-DIM compounds were structure- and cell context-dependent.CONCLUSIONS:
The results demonstrate that DIM-C-pPhC(6)H(5) and indole ring-substituted analogs are selective PPARgamma modulators.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
/
Neoplasias do Colo
/
PPAR gama
/
Indóis
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article