kh-1060 has been researched along with Adenocarcinoma* in 2 studies
2 other study(ies) available for kh-1060 and Adenocarcinoma
| Article | Year |
|---|---|
Vitamin D(3) promotes the differentiation of colon carcinoma cells by the induction of E-cadherin and the inhibition of beta-catenin signaling.
The beta-catenin signaling pathway is deregulated in nearly all colon cancers. Nonhypercalcemic vitamin D3 (1alpha,25-dehydroxyvitamin D(3)) analogues are candidate drugs to treat this neoplasia. We show that these compounds promote the differentiation of human colon carcinoma SW480 cells expressing vitamin D receptors (VDRs) (SW480-ADH) but not that of a malignant subline (SW480-R) or metastasic derivative (SW620) cells lacking VDR. 1alpha,25(OH)2D(3) induced the expression of E-cadherin and other adhesion proteins (occludin, Zonula occludens [ZO]-1, ZO-2, vinculin) and promoted the translocation of beta-catenin, plakoglobin, and ZO-1 from the nucleus to the plasma membrane. Ligand-activated VDR competed with T cell transcription factor (TCF)-4 for beta-catenin binding. Accordingly, 1alpha,25(OH)2D(3) repressed beta-catenin-TCF-4 transcriptional activity. Moreover, VDR activity was enhanced by ectopic beta-catenin and reduced by TCF-4. Also, 1alpha,25(OH)2D(3) inhibited expression of beta-catenin-TCF-4-responsive genes, c-myc, peroxisome proliferator-activated receptor delta, Tcf-1, and CD44, whereas it induced expression of ZO-1. Our results show that 1alpha,25(OH)2D(3) induces E-cadherin and modulates beta-catenin-TCF-4 target genes in a manner opposite to that of beta-catenin, promoting the differentiation of colon carcinoma cells. Topics: Active Transport, Cell Nucleus; Adenocarcinoma; Antineoplastic Agents; beta Catenin; Cadherins; Calcitriol; Cell Adhesion Molecules; Cell Differentiation; Cell Membrane; Cholecalciferol; Colonic Neoplasms; Cytoskeletal Proteins; Gene Expression Regulation, Neoplastic; Humans; Ligands; Macromolecular Substances; Phenotype; Protein Binding; Receptors, Calcitriol; RNA, Messenger; Signal Transduction; TCF Transcription Factors; Trans-Activators; Transcription Factor 7-Like 2 Protein; Transcription Factors; Transfection; Tumor Cells, Cultured; Vitamin D | 2001 |
Calcitriol and lexicalcitol (KH1060) inhibit the growth of human breast adenocarcinoma cells by enhancing transforming growth factor-beta production.
The mechanisms involved in the antiproliferative action of calcitriol (1 alpha, 25(OH)2D3) were investigated using human breast carcinoma epithelial cells (the MCF-7 cell line). Calcitriol and KH1060, a synthetic analog, inhibited cell growth in a time-and dose-dependent way. The substances similarly stimulated total TGF-beta secretion after 24 hours, and Northern blot analyses showed that mRNA levels for TGF-beta 1 were increased, as well. When MCF-7 cells were co-incubated with calcitriol and a neutralizing anti TGF-beta 1, beta 2, beta 3 antibody, growth inhibition was completely abrogated. With KH1060, the antibody could only partly block growth inhibition. This study shows that TGF-beta is involved in the growth response to calcitriol and KH1060 in MCF-7 cells. Topics: Adenocarcinoma; Breast Neoplasms; Calcitriol; Dose-Response Relationship, Drug; Female; Humans; Immunosuppressive Agents; Transforming Growth Factor beta; Tumor Cells, Cultured | 1996 |