5 alpha-reductase in intact DU145 cells: evidence for isozyme I and evaluation of novel inhibitors

Arch Pharm (Weinheim). 2000 Jul;333(7):201-4. doi: 10.1002/1521-4184(20007)333:7<201::aid-ardp201>3.0.co;2-d.

Abstract

The epithelial-like human prostatic carcinoma cell line DU145, which expresses 5 alpha-reductase type I isozyme, was used to test a series of potential 5 alpha-reductase inhibitors. The exclusive expression of the type I isozyme was confirmed by PCR and subsequent DNA sequence analysis. Culture conditions were optimized for high conversion rates. Using this whole cell assay finasteride, 4MA, and 65 steroidal and non-steroidal compounds synthesized in our group were tested for their inhibitory activity. Inhibitors with IC50 values in the nanomolar range could be identified.

MeSH terms

  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / genetics
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / metabolism
  • 5-alpha Reductase Inhibitors*
  • Drug Evaluation
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Kinetics
  • Molecular Structure
  • Sequence Analysis, DNA
  • Tumor Cells, Cultured / enzymology

Substances

  • 5-alpha Reductase Inhibitors
  • Enzyme Inhibitors
  • Isoenzymes
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase