1,1-Bis(3′-indolyl)-1-( p -substitutedphenyl)methanes Induce Peroxisome Proliferator-Activated Receptor γ-Mediated Growth Inhibition, Transactivation, and Differentiation Markers in Colon Cancer Cells

1,1-Bis(3′-indolyl)-1-(p-substituted phenyl)methanes inhibit ovarian cancer cell growth through peroxisome proliferator–activated receptor–dependent and independent pathways

“…1C. The higher growth inhibitory activity of DIM-C-pPhtBu and related compounds compared with thiazolidinediones has also been observed in bladder, colon, and pancreatic cancer cells (37,38,41).…”

“…The polyvinylidene difluoride membrane was then blocked with 5% milk in TBS-T (1.576 g/L Tris, 8.776 g/L NaCl, 0.5 mL/L Tween 20) and probed with primary antibodies, followed by incubation with horseradish peroxidase -conjugated secondary antibodies as indicated. For protein knockdown experiments, the siRNA was transfected for 36 to 48 hours before isolation of whole-cell lysates (37,38). Western blots are representatives of at least three independent experiments.…”

“…Research in this laboratory has identified a series of PPARg-active 1,1-bis(3 ¶-indolyl)-1-(p-substituted phenyl)-methanes (C-DIM; refs. 36 -41), and it was shown that growth inhibition of pancreatic and colon cancer cells was linked to PPARg-dependent induction of p21 and caveolin-1, respectively (37,38).…”

Peroxisome proliferator-activated receptor γ in bladder cancer: A promising therapeutic target

“…Several studies have shown that these compounds activate PPARγ in different cancer cell lines, such as colon, pancreatic, prostate, bladder, breast, endometrial and kidney. [101][102][103][104][105][106] Structureactivity studies show induction of PPARγ-dependent transactivation in breast cancer cell lines by these compounds, whereas treatment with the PPARγ-specific antagonist N-(4'aminopyridyl)-2-chloro-5-nitrobenzadine inhibited this effect. 101 In pancreatic cancer cell lines, ligand-dependent activation of PPARγ was observed in cells transfected with PPRE-luciferase and treated with DIM-C and troglitazone alone, whereas co-transfection of small inhibitory RNA for PPARγ, significantly inhibited transactivation by DIM-C and its effects on cell proliferation.…”

“…Additionally, these results are consistent with other studies showing that modulation of cell cycle genes (p21) and the induction of caveolin-1 have been linked to PPARγ-dependent inhibition of pancreatic and colon cancer cell growth after treatment with C-DIMs. 102,103 Nonetheless, not all effects of C-DIMs are promoted by PPARγ activation, but instead, in other responses, the C-DIMs induce pro-apoptotic and growth inhibitory effects also in a PPARγ-independent manner. 107 Currently, combined therapy has become a breakthrough in treating cancer.…”