Antiproliferative Effects of 1,25-Dihydroxyvitamin D₃ on Primary Cultures of Human Prostatic Cells

Abstract

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.