title: 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.
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-dependent induction of caveolins.
authors.affiliation: Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843-4466, USA.
authors.forename: Sudhakar
authors.initials: S
authors.lastname: Chintharlapalli
authors.forename: Roger
authors.initials: R
authors.lastname: Smith
authors.forename: Ismael
authors.initials: I
authors.lastname: Samudio
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Stephen
authors.initials: S
authors.lastname: Safe
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D018797:Cell Cycle Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008697:Methane / Q000031:analogs & derivatives* / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D014157:Transcription Factors / Q000819:agonists* / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D007211:Indoles; D018160:Receptors, Cytoplasmic and Nuclear; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone; D008697:Methane