Peroxisome Proliferator-Activated Receptor γ-Dependent Activity of Indole Ring-Substituted 11-Bis(3-indolyl)-1-(p-biphenyl)methanes in Cancer Cells

摘要

1,1-Bis(3-indolyl)-1-(p-substituted phenyl)methanes (C-DIMs) substituted in the phenyl ring with a para-, t-butyl, trifluoro or phenyl (DIM-C-pPhC6H5) group activates peroxisome proliferator-activated receptor γ (PPARγ) in several cancer cell lines. In this study, we have examined the effects of 5,5'-dihyroxy, 5,5'-dimethyl, 5,5'-dibromo, 5,5'-dinitro and 5,5'-dimethoxyindole ring substituted analogs of DIM-C-pPhC6H5 on their activity as PPARγ agonists. Introduction of the 5,5'-dihydroxy and 5,5'-dimethyl substituents enhanced activation of PPARγ 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 cells by these C-DIMs was structure- and cell context-dependent. The results demonstrate that DIM-C-pPhC6H5 and indole ring-substituted analogs are selective PPARγ modulators.