xct790 and Lung-Neoplasms

xct790 has been researched along with Lung-Neoplasms* in 2 studies

Other Studies

2 other study(ies) available for xct790 and Lung-Neoplasms

ArticleYear
Inhibition of ERRα suppresses epithelial mesenchymal transition of triple negative breast cancer cells by directly targeting fibronectin.
    Oncotarget, 2015, Sep-22, Volume: 6, Issue:28

    Triple-negative breast cancer (TNBC) patients have poor prognosis due to the aggressive metastatic behaviors. Our study reveals that expression of estrogen related receptor α (ERRα) is significantly (p < 0.01) positively associated with high grade tumors and lymph node metastasis, while negatively correlated with overall survival (OS), in 138 TNBC patients. Targeted inhibition of ERRα by its inverse agonist XCT-790 or si-RNA obviously inhibits in vitro motility of TNBC cells. While over expression of ERRα triggers the invasion and migration of TNBC cells. Further, si-ERRα and XCT-790 inhibit the epithelial mesenchymal transition (EMT) of TNBC cells with increasing the expression of E-cadherin and decreasing fibronectin (FN) and vimentin. While XCT-790 has no effect on the expression of EMT related transcription factors such as Snail or Slug. Further, inhibitors of MAPK, PI3K/Akt, NF-κB signal molecules, which are activated by XCT-790, can not attenuate the suppression effects of XCT-790 on EMT. Alternatively, luciferase reporter gene assays and ChIP analysis indicate that ERRα can directly bind with FN promoter at ERR response element-3 (ERRE-1), ERRE-3, and ERRE-4, while XCT-790 reduces this bond. In vivo data show that ERRα expression is significantly (p < 0.05) correlated with FN in clinical TNBC patients. In MDA-MB-231 tumor xenograft models, XCT-790 decreases the expression of FN, inhibits the growth and lung metastasis, and suppresses the EMT. Our results demonstrate that ERRα functions as a metastasis stimulator and its targeted inhibition may be a new therapeutic strategy for TNBC treatment.

    Topics: Animals; Antineoplastic Agents; Binding Sites; Cell Movement; Dose-Response Relationship, Drug; Drug Inverse Agonism; Epithelial-Mesenchymal Transition; ERRalpha Estrogen-Related Receptor; Female; Fibronectins; Gene Expression Regulation, Neoplastic; Hep G2 Cells; Humans; Lung Neoplasms; MCF-7 Cells; Mice, Nude; Middle Aged; Nitriles; Promoter Regions, Genetic; Protein Binding; Receptors, Estrogen; Retrospective Studies; RNA Interference; Signal Transduction; Thiazoles; Time Factors; Transfection; Triple Negative Breast Neoplasms; Xenograft Model Antitumor Assays

2015
Oestrogen-related receptor alpha inverse agonist XCT-790 arrests A549 lung cancer cell population growth by inducing mitochondrial reactive oxygen species production.
    Cell proliferation, 2010, Volume: 43, Issue:2

    Although oestrogen-related receptor alpha (ERRalpha) is primarily thought to regulate energy homeostasis, it also serves as a prognostic marker for cancer. The aim of this study was to investigate any connection between ERRalpha activity and cell population growth.. XCT-790, an ERRa specific inverse agonist, was employed to suppress ERRa activity in human non-small cell lung cancer cells (NSCLC) A549. Gene expressions were detected using quantitative real-time PCR and Western blot analysis. Mitochondrial mass, membrane potential and reactive oxygen species (ROS) production were measured by staining with Mitotracker green, JC-1 and CM-H(2)DCFDA dyes respectively. Rate of progression through the tricarboxylic acid (TCA) cycle was analysed by measuring activities of citrate synthase and succinate dehydrogenase. Cell cycle analysis was performed by using flow cytometry.. We found that XCT-790 treatment reduced mitochondrial mass but enhanced mitochondrial ROS production by increasing rate through the TCA cycle, elevating mitochondrial membrane potential (DeltaPsi(m)) and down-regulating expression of superoxide dismutase. It was further demonstrated that XCT-790-induced ROS modulated p53 and Rb signalling pathways and suppressed cell replication.. ERRalpha affects cell cycle mechanisms through modulating mitochondrial mass and function. Dysregulation of this essential pathway leads to elevation in mitochondrial ROS production, which in turn modulates activities of tumour suppressors, resulting in cell cycle arrest.

    Topics: Benzimidazoles; Carbocyanines; Carcinoma, Non-Small-Cell Lung; Cell Cycle; Cell Line, Tumor; Dose-Response Relationship, Drug; ERRalpha Estrogen-Related Receptor; Fluorescent Dyes; Humans; Lung; Lung Neoplasms; Membrane Potential, Mitochondrial; Membrane Potentials; Mitochondria; Nitriles; Reactive Oxygen Species; Receptors, Estrogen; Signal Transduction; Superoxide Dismutase; Thiazoles; Time Factors; Tumor Suppressor Protein p53

2010