1,1-Bis(3′-indolyl)-1-(p-substitutedphenyl)methanes inhibit growth, induce apoptosis, and decrease the androgen receptor in LNCaP prostate cancer cells through peroxisome proliferator-activated receptor γ-independent pathways

Sudhakar Chintharlapalli, Sabitha Papineni, Stephen Safe

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

1,1-Bis(3′-indolyl)-1-(p-substitutedphenyl)methanes (C-DIMs) containing para-trifluoromethyl, t-butyl, and phenyl groups are a novel class of peroxisome proliferator-activated receptor (PPAR)γ agonists. In LNCaP prostate cancer cells, these compounds induce PPARγ-dependent transactivation, inhibit cell proliferation, and induce apoptosis. In addition, these PPARγ agonists modulate a number of antiproliferative and proapoptotic responses, including induction of p27, activating transcription factor 3, and nonsteroidal anti-inflammatory drug-activated gene-1 and down-regulation of cyclin D1 and caveolin-1. Moreover, the PPARγ antagonist 2-chloro-5-nitrobenzanilide (GW9662) does not inhibit these effects. The C-DIM compounds also abrogate androgen receptor (AR)-mediated signaling and decrease prostate-specific antigen (PSA) and AR protein expression, and these responses were PPARγ-independent. The effects of C-DIMs on AR and PSA were due to decreased AR and PSA mRNA expression in LNCaP cells. Thus, this series of methylene-substituted diindolylmethane derivatives simultaneously activate multiple pathways in LNCaP cells, including ablation of androgen-responsiveness and down-regulation of caveolin-1. Both of these responses are associated with activation of proapoptotic pathways in this cell line.

Original languageEnglish (US)
Pages (from-to)558-569
Number of pages12
JournalMolecular Pharmacology
Volume71
Issue number2
DOIs
StatePublished - Feb 2007

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Fingerprint Dive into the research topics of '1,1-Bis(3′-indolyl)-1-(p-substitutedphenyl)methanes inhibit growth, induce apoptosis, and decrease the androgen receptor in LNCaP prostate cancer cells through peroxisome proliferator-activated receptor γ-independent pathways'. Together they form a unique fingerprint.

Cite this