Antiproliferative effects of 1,25-dihydroxyvitamin D3 on primary cultures of human prostatic cells.
Cultures of adult human prostatic epithelial and fibroblastic cells were established from normal, benign hyperplastic, and malignant tissues. Vitamin D receptors were detected by ligand binding of [3H]1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in cytosolic extracts prepared from all types of cell cultures as well as from fresh prostatic tissues. Vitamin D receptor transcripts were demonstrated by Northern blot analysis. 1,25-(OH)2D3 inhibited the growth of epithelial cells with half-maximal inhibition at approximately 1 nM. The growth of fibroblasts was also inhibited by 1,25(OH)2D3 but to a lesser extent. This is consistent with the apparently lower level of vitamin D receptors in fibroblasts compared to epithelial cells determined by ligand binding and Northern analysis of RNA transcripts. The growth inhibition of epithelial cells by 1,25(OH)2D3 was irreversible even after a short 2-h exposure, but morphology and keratin expression were not appreciably altered by long-term exposure to the hormone. A physiological role for 1,25(OH)2D3 in the prostate is postulated, and the inhibitory effect of 1,25(OH)2D3 on cancer-derived prostate cells may provide a basis for new preventive or therapeutic strategies.
Peehl
D M
DM
Department of Urology, Stanford University School of Medicine, California 94305.
Skowronski
R J
RJ
Leung
G K
GK
Wong
S T
ST
Stamey
T A
TA
Feldman
D
D
D000328:Adult; D015152:Blotting, Northern; D002117:Calcitriol / Q000378:metabolism / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007633:Keratins / Q000032:analysis / Q000502:physiology; D008297:Male; D011467:Prostate / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D011470:Prostatic Hyperplasia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D012313:RNA / Q000032:analysis; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured
D018167:Receptors, Calcitriol; D012313:RNA; D007633:Keratins; D002117:Calcitriol