Androgen Receptor Is Inactivated and Degraded in Bladder Cancer Cells by Phenyl Glucosamine via miR-449a Restoration

Med Sci Monit. 2018 Apr 16:24:2294-2301. doi: 10.12659/msm.906836.

Abstract

BACKGROUND Bladder cancer caused by exposure to aniline dyes, chronic cystitis, and smoking is detected in approximately 70 000 new cases annually. In the USA alone, it leads to 15 000 deaths every year. In the present study, we investigated the role of 3-((4'-amino-[1,1'-biphenyl]-4-yl)amino)-4-bromo-5-oxo-2,5-dihydrofuran-2-yl acetate (ABDHFA) in the inhibition of bladder cancer cell viability. MATERIAL AND METHODS Viability of cells was examined using MTT assay and distribution of cell cycle was assessed by flow cytometry. Expression of cyclin D1, androgen, prostate-specific antigen (PSA), and miR-449a was analyzed using Western blot and quantitative real-time polymerase chain reaction assays. RESULTS The results demonstrated that ABDHFA treatment inhibited viability of UMUC3 and TCCSUP AR-positive bladder cancer cells. ABDHFA treatment led to break-down of AR in UMUC3 and TCCSUP cells after 48 h in a dose-dependent manner. Up-regulation of miR-449a by lentivirus transfection down-regulated the AR signalling pathway. In UMUC3 and TCCSUP cells, ABDHFA treatment led to inhibition of mRNA and protein expression corresponding to AR. CONCLUSIONS In summary, the present study demonstrates that proliferation of AR-positive bladder carcinoma cells is markedly reduced by ABDHFA treatment through arrest of cell cycle and degradation of AR protein. Thus, ABDHFA, a novel compound, can be used for the treatment of bladder cancer.

MeSH terms

  • Acetates / pharmacology
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cyclin D1 / biosynthesis
  • Cyclin D1 / genetics
  • Furans / pharmacology
  • Glucosamine / pharmacology*
  • Humans
  • Kallikreins / biosynthesis
  • Kallikreins / genetics
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Prostate-Specific Antigen / biosynthesis
  • Prostate-Specific Antigen / genetics
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism*
  • Signal Transduction
  • Up-Regulation
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / pathology

Substances

  • AR protein, human
  • Acetates
  • CCND1 protein, human
  • Furans
  • MIRN449 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Receptors, Androgen
  • Cyclin D1
  • KLK3 protein, human
  • Kallikreins
  • Prostate-Specific Antigen
  • Glucosamine