1,1-Bis(3'-indolyl)-1-(p-substitutedphenyl)methanes are peroxisome proliferator-activated receptor gamma 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.
Peroxisome proliferator-activated receptor gamma (PPAR-gamma), a member of the nuclear hormone receptor superfamily, is involved in suppression of growth of several types of tumors such as liposarcoma, breast cancer, prostate cancer, and colon cancer, possibly through induction of cell cycle arrest and/or apoptosis.
Peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the nuclear receptor superfamily, plays a role in adipocyte differentiation, type II diabetes, macrophage response to inflammation and is suggested to influence carcinogen-induced colon cancer.
Based on our findings, p38 MAPK and transcription factor PPARgamma can be considered as molecular targets of resveratrol in the regulation of cell proliferation and SSAT activity, respectively, in a cell culture model of colon cancer.
Comparison of the transcriptome data of metastasis-competent CTC-MCC-41 cells and of HT-29 cells (derived from a primary colon cancer) highlights the differential expression of genes that regulate energy metabolism [peroxisome proliferator-activated receptor γ coactivator 1A (<i>PPARGC1A</i>), peroxisome proliferator-activated receptor γ coactivator 1B (<i>PPARGC1B</i>), fatty acid binding protein 1 (<i>FABP1</i>), aldehyde dehydrogenase 3 family member A1 (<i>ALDH3A1</i>)], DNA repair [BRCA1 interacting protein C-terminal helicase 1 (<i>BRIP1</i>), Fanconi anemia complementation group B (<i>FANCB</i>), Fanconi anemia complementation group M (<i>FANCM</i>)], and stemness [glutaminase 2 (<i>GLS2</i>), cystathionine-beta-synthase (<i>CBS</i>), and cystathionine gamma-lyase (<i>CTH</i>)].
Finally, EPA suppressed HT-29 cell growth and this effect was significantly reversed by the addition of GW, suggesting that in part the physiological actions of EPA are the result of PPARgamma activation.
High lutein intake [odds ratio (OR), 0.63; 95% confidence interval (95% CI), 0.44-0.89], low refined grain intake (OR, 0.70; 95% CI, 0.53-0.94), or a high prudent diet score (OR, 0.66; 95% CI, 0.49-0.89) and PA/AA PPARgamma genotype were associated with reduced colon cancer risk.
However, only retroviral transduction of the wild-type (WT), but not mutant, receptor could restore PPARgamma ligand-induced growth inhibition and differentiation in resistant colon cancer cell lines.
In addition, FPLD3-associated PPARγ mutations consistently cause intra- and/or intermolecular defects; colon cancer-associated PPARγ mutations on the other hand may play a role in colon cancer onset and progression, but this is not due to their effects on the most well-studied functional characteristics of PPARγ.
In conclusion, SOX9, β-catenin and PPARγ expression levels are deregulated in the CRC tissue, and in colon cancer cell lines ligand-dependent PPARγ activation unevenly influences SOX9 and β-catenin expression and subcellular localization, suggesting a variable mechanistic role in colon carcinogenesis.
Our findings suggest that PPARgamma plays a role as a physiological regulator of colonic epithelial cell turnover and consequently predisposition to the development of colon cancer in early stage.
Peroxisome proliferator-activated receptor (PPAR) gamma is expressed in human colon cancer, prostate cancer and breast cancer cells, and PPARgamma activation induces growth inhibition in these cells.
Stratified meta-analysis indicated that PPAR-gamma 34 C>G was associated with colon cancer (OR = 0.8, 95% CI: 0.65-0.99, P = 0.04) in random-effect model, and the G allele decreased colon cancer risk.
The activation of peroxisome proliferator-activated receptor gamma stimulated by thiazolidinedione is useful in the treatment of type II diabetes mellitus and may have value in preventing inflammatory bowel disease or colon cancer.
The molecules and signals that act to eradicate or initiate the apoptosis cascade in cancer cells, are elucidated, and these include caspases, Fas, Bax, Bid, APC, antisense hTERT, PUMA, 15-LOX-1, ceramide, butyrate, tributyrin and PPARgamma, whereas the molecules which promote colon cancer cell survival are p53 mutants, Bcl-2, Neu3 and COX-2.
The odd ratio for PPARgamma PA or AA genotype relative to the PP genotype for colon cancer was 0.9 (95% confidence interval, CI=0.8-1.0) and for rectal cancer was 1.2 (95% CI=1.0-1.5) adjusting for race, age, and sex.