Antiproliferative effect of calcitriol on human prostatic cancer cell lines: unrelated to the expression of major histocompatibility complex antigens or intercellular adhesion molecule-1 (ICAM-1).
BACKGROUND
In addition to its role in calcium and phosphorus metabolism, calcitriol (1,25-dihydroxyvitamin D3; 1,25-D3) demonstrates multiple effects on cell proliferation/differentiation by expressing major histocompatibility complex (MHC) antigens and intercellular adhesion molecule-1 (ICAM-1). It has recently been reported that 1,25-D3 inhibits the growth of prostatic cancer (PCa) cells. In this study we examined the effect of 1,25-D3 on both the growth and expression of HLA-ABC, HLA-DR and ICAM-1 antigens in PCa cells.


METHODS
Four human PCa cell lines (PC-3, PPC-1, ALVA-41 and ALVA-101) were examined. The cell numbers were enumerated, and the effects of interferon-y (IFN-gamma) and 1,25-D3 on the expression of HLA-ABC, HLA-DR and ICAM-1 were quantitated by flow cytometry.


RESULTS
A dose-dependent antiproliferative effect of 1,25-D3 was found in all PCa cells lines except ALVA-41.1,25-D3 was approximately 10 times as potent as its analogue 24,25-dihydroxyvitamin D3 in inhibiting the growth of PC-3 cells. Also, the relative inhibitory ability of these compounds paralleled the strength of their binding affinities for the 1,25-D3 receptor, indicating that the antiproliferative effect may require a receptor-ligand interaction. HLA-ABC was expressed in PC-3, ALVA-41 and ALVA-101, but not in PPC-1 cells, while HLA-DR was not expressed on any of the tested cells. IFN-gammacould enhance or induce HLA-ABC but not HLA-DR expression in the tested cells. ICAM-1 was expressed in all cells and slightly upregulated by IFN-gamma.


CONCLUSIONS
In this study 1,25-D3 had an antiproliferative effect on 3 of the 4 examined PCa cell lines.
Yu
D M
DM
Department of Urology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Tokuda
N
N
Naito
S
S
Yoshikawa
M
M
Takahashi
K
K
Uozumi
J
J
Kumazawa
J
J
D015650:24,25-Dihydroxyvitamin D 3 / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006680:HLA Antigens / Q000096:biosynthesis*; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000494:pharmacology; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D014407:Tumor Cells, Cultured
D006680:HLA Antigens; D006684:HLA-DR Antigens; D018799:Intercellular Adhesion Molecule-1; D015650:24,25-Dihydroxyvitamin D 3; D007371:Interferon-gamma; D002117:Calcitriol