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Peroxisome proliferator-activated receptor gamma-dependent activity of indole ring-substituted 1,1-bis(3'-indolyl)-1-(p-biphenyl)methanes in cancer cells.

Authors :
Guo J
Chintharlapalli S
Lee SO
Cho SD
Lei P
Papineni S
Safe S
Guo, Jingjing
Chintharlapalli, Sudhakar
Lee, Syng-ook
Cho, Sung Dae
Lei, Ping
Papineni, Sabitha
Safe, Stephen
Source :
Cancer Chemotherapy & Pharmacology; 2010 May, Vol. 66 Issue 1, p141-150, 10p
Publication Year :
2010

Abstract

<bold>Purpose: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>The results demonstrate that DIM-C-pPhC(6)H(5) and indole ring-substituted analogs are selective PPARgamma modulators. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
03445704
Volume :
66
Issue :
1
Database :
Complementary Index
Journal :
Cancer Chemotherapy & Pharmacology
Publication Type :
Academic Journal
Accession number :
105177609
Full Text :
https://doi.org/10.1007/s00280-009-1144-0