Des (1-3) IGF-I-stimulated growth of human stromal BPH cells is inhibited by a vitamin D3 analogue.
Prostate growth and differentiation is under the control of androgens not only during fetal life and childhood but also in adulthood, and it has been proposed that increased prostatic concentration of androgens, or increased androgen responsiveness, causes benign prostatic hyperplasia (BPH). However, different androgen ablation strategies such as treatment with GnRH agonists and finasteride resulted in a modest decrease of the hyperplastic prostate volume. In the last few years it became evident that both androgen-dependent and androgen-independent growth factors promote prostate enlargement by inducing cell proliferation or reducing apoptosis. Therefore, new therapeutic strategies, aimed at reducing intraprostatic growth factor signaling, are under investigation. In this study, we report further evidence that a non hypercalcemic-analogue of vitamin D(3), analogue (V) decreases growth factor-induced human BPH cell proliferation and survival. We found that Des (1-3) insulin-like growth factor [Des (1-3) IGF-I], an IGF-I analogue, which does not bind to IGF-binding proteins, is a potent mitogen for BPH stromal cells via a dual mechanism: stimulation of cell growth and inhibition of apoptosis. Similar results were previously reported for another growth factor for BPH cells, keratinocyte growth factor (KGF). Accordingly, we speculate that both KGF and IGF might be involved in the pathogenesis of BPH. We also found analogue (V) not only inhibits the mitogenic activity of growth factors on BPH cells, but even decreased the basal expression of bcl-2, and induced apoptosis. Therefore, vitamin D(3) analogues might be considered for the medical treatment of BPH.
Crescioli
C
C
Endocrinology Unit, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
Villari
D
D
Forti
G
G
Ferruzzi
P
P
Petrone
L
L
Vannelli
G B
GB
Adorini
L
L
Salerno
R
R
Serio
M
M
Maggi
M
M
D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D011470:Prostatic Hyperplasia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017154:Stromal Cells / Q000473:pathology / Q000502:physiology*
D010446:Peptide Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; C058957:insulin-like growth factor 1, des-(1-3)-; D002762:Cholecalciferol; D007334:Insulin-Like Growth Factor I