Inhibition of the enzymatic activity of prostate-specific antigen by boric acid and 3-nitrophenyl boronic acid.
BACKGROUND
Prostate specific antigen (PSA) is a well-established marker of prostate cancer, but it can also degrade extracellular matrix proteins such as fibronectin and could be involved in tumor progression and metastasis. In this study, we have addressed the use of boric acid and 3-nitrophenyl boronic acid (NPBA) as PSA inhibitors in vitro.


METHODS
The inhibition of PSA by boric acid was studied by using specific fluorogenic substrates. Fibronectin, a biologically relevant substrate for PSA, was used as a substrate in a zymographic assay, and the degradation of fibronectin by PSA in the presence of boric acid and NPBA was followed by Western Blot.


RESULTS
Low concentrations of boric acid partially inhibited the proteolytic activity of PSA toward a synthetic fluorogenic substrate. Also, by Western blot, we have found significant inhibition in the proteolysis of fibronectin by PSA in the presence of boric acid as well as NPBA. Results indicate that the boronated compounds used in this study can be used for the modulation of PSA activity.


CONCLUSIONS
PSA activity is inhibited in vitro by boric acid and NPBA. If degradation of fibronectin by PSA were, in fact, an important step in the progression of prostate cancer, then borate-induced inhibition of PSA activity should help reduce the development and proliferation of prostate carcinomas.
Gallardo-Williams
Maria T
MT
Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. gallardo@niehs.nih.gov
Maronpot
Robert R
RR
Wine
Robert N
RN
Brunssen
Susan H
SH
Chapin
Robert E
RE
D015153:Blotting, Western; D001888:Boric Acids / Q000494:pharmacology*; D001897:Boronic Acids / Q000494:pharmacology*; D002455:Cell Division; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007306:Insecticides / Q000494:pharmacology*; D008297:Male; D017430:Prostate-Specific Antigen / Q000187:drug effects* / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000503:physiopathology*; D012697:Serine Endopeptidases / Q000494:pharmacology
D001888:Boric Acids; D001897:Boronic Acids; D004791:Enzyme Inhibitors; D005353:Fibronectins; D007306:Insecticides; C017562:3-nitrobenzeneboronic acid; D012697:Serine Endopeptidases; D017430:Prostate-Specific Antigen; C032688:boric acid