Human prostate cells synthesize 1,25-dihydroxyvitamin D 3 from 25- hydroxyvitamin D 3

Gary Schwartz, Lyman W. Whitlatch, Tai C. Chen, Bal L. Lokeshwar, Michael F. Holick

Research output: Contribution to journalArticle

307 Citations (Scopus)

Abstract

Epidemiological and laboratory data support a role for vitamin D in the growth and differentiation of human prostatic cells. These findings prompted us to ask whether prostatic cells could convert 25-hydroxyvitamin D 3 (25- OH-D 3 ), the major circulating metabolite of vitamin D 3 , to 1,25- dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ], the hormonally active metabolite, in a manner similar to cultured human keratinocytes. Therefore, we investigated three well-characterized human prostate cancer cell lines, LNCaP, DU 145, and PC-3; two primary cultures of cells derived from noncancerous human prostates (one normal and one benign prostatic hyperplasia); and primary cultures of normal human keratinocytes for their ability to synthesize 1,25(OH) 2 D 3 . Assays were performed in the presence of 25-OH-D 3 as the enzyme substrate and 1,2-dianilinoethane, an antioxidant and free radical scavenger, and in the presence and absence of clotrimazole, a cytochrome P450 inhibitor. DU 145 and PC-3 cells produced 0.31 ± 0.06 and 0.07 ± 0.01 pmol of 1,25(OH) 2 D 3 /mg protein/h, respectively. No measurable 1,25(OH) 2 D 3 was detected in LNCaP cells. The normal and benign prostatic hyperplasia primary cultures and keratinocyte cultures produced 3.08 ± 1.56, 1.05 ± 0.31, and 2.1 ± 0.1 pmol of 1,25(OH) 2 D 3 /mg protein/h, respectively, using a calf thymus receptor binding assay to measure 1,25(OH) 2 D 3 in the presence of 1,2-dianilinoethane. The identity of the analyte as 1,25(OH) 2 D 3 was supported by high performance liquid chromatography using [ 3 H]25-OH-D 3 as the enzyme substrate and a solvent system that is specific for 1,25(OH) 2 D 3 . The production of 1,25(OH) 2 D 3 in the prostate cancer cell lines and in the primary cultures was completely inhibited in the presence of clotrimazole. This report demonstrates that two of three human prostate cancer cell lines, as well as primary cultures of noncancerous prostatic cells, possess 1α- hydroxylase activity and can synthesize 1,25(OH) 2 D 3 from 25-OH-D 3 . Together with recent data indicating that 1,25(OH) 2 D 3 inhibits the invasiveness of human prostate cancer cells (G. G. Schwartz et al., Cancer Epidemiol. Biomark. Prev., 6: 727-732, 1997), these data suggest a potential role for 25-OH-D 3 in the chemoprevention of invasive prostate cancer.

Original languageEnglish (US)
Pages (from-to)391-395
Number of pages5
JournalCancer Epidemiology Biomarkers and Prevention
Volume7
Issue number5
StatePublished - May 1 1998

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Calcifediol
Prostate
Prostatic Neoplasms
Keratinocytes
Clotrimazole
Prostatic Hyperplasia
Cell Line
Free Radical Scavengers
Primary Cell Culture
Cholecalciferol
Chemoprevention
Enzymes
Mixed Function Oxygenases
1,25-dihydroxyvitamin D
Vitamin D
Cytochrome P-450 Enzyme System
Thymus Gland
Proteins
Antioxidants
High Pressure Liquid Chromatography

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Human prostate cells synthesize 1,25-dihydroxyvitamin D 3 from 25- hydroxyvitamin D 3 . / Schwartz, Gary; Whitlatch, Lyman W.; Chen, Tai C.; Lokeshwar, Bal L.; Holick, Michael F.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 7, No. 5, 01.05.1998, p. 391-395.

Research output: Contribution to journalArticle

Schwartz, Gary ; Whitlatch, Lyman W. ; Chen, Tai C. ; Lokeshwar, Bal L. ; Holick, Michael F. / Human prostate cells synthesize 1,25-dihydroxyvitamin D 3 from 25- hydroxyvitamin D 3 In: Cancer Epidemiology Biomarkers and Prevention. 1998 ; Vol. 7, No. 5. pp. 391-395.
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abstract = "Epidemiological and laboratory data support a role for vitamin D in the growth and differentiation of human prostatic cells. These findings prompted us to ask whether prostatic cells could convert 25-hydroxyvitamin D 3 (25- OH-D 3 ), the major circulating metabolite of vitamin D 3 , to 1,25- dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ], the hormonally active metabolite, in a manner similar to cultured human keratinocytes. Therefore, we investigated three well-characterized human prostate cancer cell lines, LNCaP, DU 145, and PC-3; two primary cultures of cells derived from noncancerous human prostates (one normal and one benign prostatic hyperplasia); and primary cultures of normal human keratinocytes for their ability to synthesize 1,25(OH) 2 D 3 . Assays were performed in the presence of 25-OH-D 3 as the enzyme substrate and 1,2-dianilinoethane, an antioxidant and free radical scavenger, and in the presence and absence of clotrimazole, a cytochrome P450 inhibitor. DU 145 and PC-3 cells produced 0.31 ± 0.06 and 0.07 ± 0.01 pmol of 1,25(OH) 2 D 3 /mg protein/h, respectively. No measurable 1,25(OH) 2 D 3 was detected in LNCaP cells. The normal and benign prostatic hyperplasia primary cultures and keratinocyte cultures produced 3.08 ± 1.56, 1.05 ± 0.31, and 2.1 ± 0.1 pmol of 1,25(OH) 2 D 3 /mg protein/h, respectively, using a calf thymus receptor binding assay to measure 1,25(OH) 2 D 3 in the presence of 1,2-dianilinoethane. The identity of the analyte as 1,25(OH) 2 D 3 was supported by high performance liquid chromatography using [ 3 H]25-OH-D 3 as the enzyme substrate and a solvent system that is specific for 1,25(OH) 2 D 3 . The production of 1,25(OH) 2 D 3 in the prostate cancer cell lines and in the primary cultures was completely inhibited in the presence of clotrimazole. This report demonstrates that two of three human prostate cancer cell lines, as well as primary cultures of noncancerous prostatic cells, possess 1α- hydroxylase activity and can synthesize 1,25(OH) 2 D 3 from 25-OH-D 3 . Together with recent data indicating that 1,25(OH) 2 D 3 inhibits the invasiveness of human prostate cancer cells (G. G. Schwartz et al., Cancer Epidemiol. Biomark. Prev., 6: 727-732, 1997), these data suggest a potential role for 25-OH-D 3 in the chemoprevention of invasive prostate cancer.",
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AU - Schwartz, Gary

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AU - Lokeshwar, Bal L.

AU - Holick, Michael F.

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N2 - Epidemiological and laboratory data support a role for vitamin D in the growth and differentiation of human prostatic cells. These findings prompted us to ask whether prostatic cells could convert 25-hydroxyvitamin D 3 (25- OH-D 3 ), the major circulating metabolite of vitamin D 3 , to 1,25- dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ], the hormonally active metabolite, in a manner similar to cultured human keratinocytes. Therefore, we investigated three well-characterized human prostate cancer cell lines, LNCaP, DU 145, and PC-3; two primary cultures of cells derived from noncancerous human prostates (one normal and one benign prostatic hyperplasia); and primary cultures of normal human keratinocytes for their ability to synthesize 1,25(OH) 2 D 3 . Assays were performed in the presence of 25-OH-D 3 as the enzyme substrate and 1,2-dianilinoethane, an antioxidant and free radical scavenger, and in the presence and absence of clotrimazole, a cytochrome P450 inhibitor. DU 145 and PC-3 cells produced 0.31 ± 0.06 and 0.07 ± 0.01 pmol of 1,25(OH) 2 D 3 /mg protein/h, respectively. No measurable 1,25(OH) 2 D 3 was detected in LNCaP cells. The normal and benign prostatic hyperplasia primary cultures and keratinocyte cultures produced 3.08 ± 1.56, 1.05 ± 0.31, and 2.1 ± 0.1 pmol of 1,25(OH) 2 D 3 /mg protein/h, respectively, using a calf thymus receptor binding assay to measure 1,25(OH) 2 D 3 in the presence of 1,2-dianilinoethane. The identity of the analyte as 1,25(OH) 2 D 3 was supported by high performance liquid chromatography using [ 3 H]25-OH-D 3 as the enzyme substrate and a solvent system that is specific for 1,25(OH) 2 D 3 . The production of 1,25(OH) 2 D 3 in the prostate cancer cell lines and in the primary cultures was completely inhibited in the presence of clotrimazole. This report demonstrates that two of three human prostate cancer cell lines, as well as primary cultures of noncancerous prostatic cells, possess 1α- hydroxylase activity and can synthesize 1,25(OH) 2 D 3 from 25-OH-D 3 . Together with recent data indicating that 1,25(OH) 2 D 3 inhibits the invasiveness of human prostate cancer cells (G. G. Schwartz et al., Cancer Epidemiol. Biomark. Prev., 6: 727-732, 1997), these data suggest a potential role for 25-OH-D 3 in the chemoprevention of invasive prostate cancer.

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