1,1-Bis(3′-indolyl)-1-(p-substitutedphenyl)methanes Are Peroxisome Proliferator-Activated Receptor γ Agonists but Decrease HCT-116 Colon Cancer Cell Survival through Receptor-Independent Activation of Early Growth Response-1 and Nonsteroidal Anti-Inflammatory Drug-Activated Gene-1

• DOI: 10.1124/mol.105.017046
• Publication Date: 2005-09-10T00:34:07Z
• Authors: Sudhakar Chinthar...; Sabitha Papineni; Seung Joon Baek; Shengxi Liu; Stephen Safe
• Keywords: Growth inhibition

1,1-Bis-(3′-indolyl)-1-(<i>p</i>-substitutedphenyl)methanes containing <i>p</i>-trifluoromethyl (DIM-C-pPhCF₃), <i>p-t</i>-butyl (DIM-C-pPhtBu), and phenyl (DIM-C-pPhC₆H₅) substituents decrease survival of HCT-116 colon cancer cells activate peroxisome proliferator-activated receptor (PPAR) γ in this other cell lines. These PPARγ-active compounds had minimal effects on expression cycle proteins did not induce caveolin-1 cells. However, these induced nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) apoptosis cells, time-course studies, the PPARγ agonists maximally early growth response-1 (Egr-1) protein within 2 h, whereas a longer time course was observed for induction NAG-1 protein. data, coupled with deletion mutation analysis both Egr-1 gene promoters, indicate that activation by dependent prior Egr-1, responses PPARγ-independent. Results kinase inhibitor studies also demonstrated Egr-1/NAG-1 methylene-substituted diindolylmethanes (C-DIMs) phosphatidylinositol 3-kinase-dependent, represents novel receptor-independent pathway C-DIM-induced inhibition