Compound A Inhibits Bladder Cancer Growth Predominantly via Glucocorticoid Receptor Transrepression

Molecular Endocrinology
Yichun ZhengHiroshi Miyamoto

Abstract

Recent evidence indicates that glucocorticoids (GCs) suppress bladder cancer cell invasion through the GC receptor (GR) pathway, whereas androgen-mediated androgen receptor (AR) signals induce bladder tumor progression. In this study, we assessed the effects of 2-(4-acetoxyphenyl)-2-chloro-N-methyl-ethylammonium chloride (compound A [CpdA]), which was shown to function as not only a GR modulator but also an AR antagonist, on the growth of bladder cancer. In GR/AR-positive cells, CpdA strongly inhibited cell proliferation and colony formation as well as increased G1 phase-arrested cell population and apoptosis. Specifically, CpdA at 1μM decreased cell viability of TCCSUP/UMUC3-control-short hairpin RNA (shRNA), TCCSUP/UMUC3-GR-shRNA, and TCCSUP/UMUC3-AR-shRNA by 50%/67%, 25%/26%, and 38%/58%, respectively. CpdA also inhibited cell migration and invasion of GR/AR-positive (up to 61% decrease) and GR-positive/AR-silencing (up to 51% decrease) lines and, less strongly, those of GR-silencing/AR-positive lines (up to 35% decrease). Additionally, in UMUC3-control xenograft-bearing male mice, CpdA more strongly suppressed tumor growth than dexamethasone or hydroxyflutamide. In reporter gene assays, CpdA failed to induce GR transactivat...Continue Reading

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Citations

Jan 16, 2016·Disease Markers·Hiroki Ide, Hiroshi Miyamoto
Jul 9, 2016·European Journal of Pharmacology·Adnan Dibas, Thomas Yorio
Jan 10, 2017·Expert Opinion on Therapeutic Targets·Taichi MizushimaHiroshi Miyamoto
Jun 28, 2017·Molecular and Cellular Endocrinology·Satoshi InoueHiroshi Miyamoto
Jul 23, 2016·Oncotarget·Takashi KawaharaHiroshi Miyamoto
Mar 1, 2017·Cancers·Peng LiHiroshi Miyamoto
Aug 8, 2020·Cancers·Hiroki Ide, Hiroshi Miyamoto

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