1,1-Bis(3'-indolyl)-1-(p-substitutedphenyl)methanes induce peroxisome proliferator-activated receptor gamma-mediated growth inhibition, transactivation, and differentiation markers in colon cancer cells

Cancer Research
Sudhakar ChintharlapalliStephen Safe

Abstract

1,1-Bis(3'indolyl)-1-(p-substitutedphenyl)methanes containing p-trifluoromethyl (DIM-C-pPhCF)), p-t-butyl (DIM-C-pPhtBu), and p-phenyl (DIM-C-pPhC6H5) groups induce peroxisome proliferator-activated receptor gamma (PPARgamma)-mediated transactivation in HT-29, HCT-15, RKO, and SW480 colon cancer cell lines. Rosiglitazone also induces transactivation in these cell lines and inhibited growth of HT-29 cells, which express wild-type PPARgamma but not HCT-15 cells, which express mutant (K422Q) PPARgamma. In contrast, DIM-C-pPhCF3, DIM-C-pPhtBu, and DIM-C-pPhC6H5 inhibited growth of both HT-29 and HCT-15 cells with IC50 values ranging from 1 to 10 micromol/L. Rosiglitazone and diindolylmethane (DIM) analogues did not affect expression of cyclin D1, p21, or p27 protein levels or apoptosis in HCT-15 or HT-29 cells but induced keratin 18 in both cell lines. However, rosiglitazone induced caveolins 1 and 2 in HT-29 but not HCT-15 cells, whereas these differentiation markers were induced by DIM-C-pPhCF3 and DIM-C-pPhC6H5 in both cell lines. Because overexpression of caveolin 1 is known to suppress colon cancer cell and tumor growth, the growth inhibitory effects of rosiglitazone and the DIM compounds are associated with PPARgamma-dependen...Continue Reading

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Citations

Jul 31, 2007·Journal of Cancer Research and Clinical Oncology·Ioannis A Voutsadakis
Jan 17, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Nkechi IchiteMandip Singh
Jul 23, 2008·Molecular Cancer Therapeutics·Sung Dae ChoStephen Safe
Oct 28, 2010·Molecular Cancer Therapeutics·Nkechi IchiteMandip Singh
Sep 4, 2007·Breast Cancer Research : BCR·Yunpeng SuArthur E Frankel
May 29, 2014·Pharmaceutical Research·Apurva R PatelMandip Singh
Jan 6, 2011·Expert Opinion on Therapeutic Targets·Syng-Ook LeeStephen Safe
Jun 13, 2015·Oncology Reports·Khalda FadlallaTemesgen Samuel
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Nov 12, 2016·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Morgan S BridiTed Abel
Jun 17, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Apurva R PatelMandip Singh
May 6, 2005·The Journal of Biological Chemistry·Sudhakar ChintharlapalliStephen Safe
Apr 11, 2008·Journal of Cellular and Molecular Medicine·Andrew F G QuestVicente A Torres
Dec 4, 2013·Molecular Endocrinology·Stephen SafeSyng-Ook Lee
Nov 17, 2009·The FEBS Journal·Huimin LuGuangmei Yan
Nov 17, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Melissa YorkStephen Safe
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May 27, 2008·Cancer Letters·Stephen SafeSudhakar Chintharlapalli
Oct 17, 2021·Genome Biology·Xiaobo KeRamnik J Xavier

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