Lovastatin-Induced Apoptosis in Prostate Stromal Cells
Benign prostatic hyperplasia (BPH) is a common disease of aging men. Current medical treatment for this condition is only partially effective, therefore many patients must undergo surgery for symptomatic relief. BPH is caused by an increase in prostate epithelial and stromal cells, especially the la...
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Published in | The journal of clinical endocrinology and metabolism Vol. 82; no. 5; pp. 1434 - 1439 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Endocrine Society
01.05.1997
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Online Access | Get full text |
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Summary: | Benign prostatic hyperplasia (BPH) is a common disease of aging men.
Current medical treatment for this condition is only partially
effective, therefore many patients must undergo surgery for symptomatic
relief. BPH is caused by an increase in prostate epithelial and stromal
cells, especially the latter. Since BPH stromal cells have a long life
span and are not very responsive to androgen withdrawal, cultured BPH
stromal cells were used to explore the feasibility of pharmacologically
inducing apoptosis in these cells.
We obtained BPH tissue during surgery, and stromal cells were isolated
and maintained in culture. After cells achieved confluence, we induced
apoptosis with the HMGCoA reductase inhibitor, lovastatin (30μ
mol/L). The effects of testosterone (100 μmol/L),
dihydrotestosterone (DHT; 100 μmol/L) and finasteride (100 μmol/L)
on lovastatin-induced apoptosis were studied on cells grown in media
containing charcoal stripped serum. Similarly, we examined the effect
of the cholesterol pathway metabolites, mevalonic acid (30 μmol/L),
geranyl geraniol (30 μmol/L), farnesol (10 μmol/L), squalene (30μ
mol/L) and 7-ketocholesterol (3 μmol/L) on lovastatin-induced
apoptosis. We demonstrated apoptosis by DNA laddering in agarose gels,
by fluorescence microscopy following acridine orange staining, and by
flow cytometry after end-labeling of DNA strand breaks with
biotin-16-dUTP using deoxynucleotidyl exotransferase (TdT).
Lovastatin at 30 μmol/L, but not at lower concentrations, induced
apoptosis in BPH prostate stromal cells. This was seen (by flow
cytometry) in 16.6 ± 7.3% (mean ± sd) of BPH
cells treated with lovastatin at 72 h vs. 2.5±
1.2% of cells treated with ethanol. Lovastatin-induced apoptosis
was not increased in stripped serum or by the addition finasteride, and
was not inhibited by testosterone or DHT. Only mevalonate and geranyl
geraniol, prevented lovastatin-induced apoptosis whereas farnesol,
squalene, or 7-ketocholesterol did not.
We conclude that lovastatin can induce apoptosis in BPH stromal cells
in vitro, and this is not affected by androgen
withdrawal or stimulation. It is unlikely that lovastatin, per
se, will be an effective treatment for BPH in
vivo, but it does provide a means for inducing apoptosis
in vitro. Understanding the apoptotic process in BPH
stromal cells ultimately may lead to new therapeutic strategies for
BPH. |
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ISSN: | 0021-972X 1945-7197 |
DOI: | 10.1210/jcem.82.5.3960 |