PMID- 14648702
OWN - NLM
STAT- MEDLINE
DCOM- 20040123
LR  - 20191210
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 108
IP  - 3
DP  - 2004 Jan 20
TI  - Role of 24-hydroxylase in vitamin D3 growth response of OVCAR-3 ovarian cancer 
      cells.
PG  - 367-73
AB  - Vitamin D and its analogues are potent regulators of cell growth and 
      differentiation both in vivo and in vitro. We studied the effects of 
      25-hydroxyvitamin D(3) [25(OH)D(3)], 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] 
      and vitamin D analogue, EB 1089, on the growth of a human ovarian cancer cell 
      line, OVCAR-3. We also studied the expression of vitamin D metabolising enzymes 
      24-hydroxylase (24OHase) and 1alpha-hydroxylase (1alphaOHase). Our results showed 
      that high concentrations (10 and 100 nM) of 1,25(OH)(2)D(3) inhibited a cell 
      proliferation, whereas low concentration (0.1 nM) stimulated growth of the 
      OVCAR-3 cells. In the concentration range of 10-500 nM a prohormone, 25(OH)D(3), 
      stimulated growth. An amount of 1 nM EB 1089 and 100 nM 1,25(OH)(2)D(3) inhibited 
      growth with an equal magnitude. The expression of 24OHase was strongly induced by 
      1,25(OH)(2)D(3) and EB 1089 in OVCAR-3 cells, and analysis of vitamin D 
      metabolites showed the functionality of 24OHase. An inhibition of 24OHase 
      activity with a novel 24OHase inhibitor enhanced growth-inhibiting effects of 
      1,25(OH)(2)D(3) and suppressed the growth stimulation of 100 nM 25(OH)D(3). We 
      also report the expression of a vitamin D activating enzyme, 1alphaOHase, in 7 
      ovarian cancer cell lines. The production of 1,25(OH)(2)D(3) in OVCAR-3 cells was 
      low, possibly due to an extensive activity of 24OHase or a low 1alphaOHase 
      activity. These results suggest that in ovarian cancer cells vitamin D 
      metabolizing enzymes might play a key role in modulating the growth response to 
      vitamin D. The possible mitogenic effects of vitamin D should be considered when 
      evaluating treatment of ovarian cancer with vitamin D.
CI  - Copyright 2003 Wiley-Liss, Inc.
FAU - Miettinen, Susanna
AU  - Miettinen S
AD  - Department of Cell Biology, Medical School, University of Tampere, Tampere, 
      Finland. susanna.miettinen@uta.fi
FAU - Ahonen, Merja H
AU  - Ahonen MH
FAU - Lou, Yan-Ru
AU  - Lou YR
FAU - Manninen, Tommi
AU  - Manninen T
FAU - Tuohimaa, Pentti
AU  - Tuohimaa P
FAU - Syvala, Heimo
AU  - Syvala H
FAU - Ylikomi, Timo
AU  - Ylikomi T
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Cytochrome P-450 Enzyme Inhibitors)
RN  - 0 (Enzyme Inhibitors)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - EC 1.14.- (Steroid Hydroxylases)
RN  - EC 1.14.15.16 (Vitamin D3 24-Hydroxylase)
RN  - EC 1.14.15.18 (25-Hydroxyvitamin D3 1-alpha-Hydroxylase)
RN  - FXC9231JVH (Calcitriol)
RN  - P6YZ13C99Q (Calcifediol)
RN  - Q0OZ0D9223 (seocalcitol)
SB  - IM
MH  - 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/antagonists & inhibitors/metabolism
MH  - Calcifediol/*pharmacology
MH  - Calcitriol/*analogs & derivatives/*pharmacology
MH  - Cell Division/drug effects
MH  - Cytochrome P-450 Enzyme Inhibitors
MH  - Cytochrome P-450 Enzyme System/*metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Female
MH  - Humans
MH  - Ovarian Neoplasms/*enzymology/pathology
MH  - Steroid Hydroxylases/antagonists & inhibitors/*metabolism
MH  - Tumor Cells, Cultured
MH  - Vitamin D3 24-Hydroxylase
EDAT- 2003/12/04 05:00
MHDA- 2004/01/24 05:00
CRDT- 2003/12/04 05:00
PHST- 2003/12/04 05:00 [pubmed]
PHST- 2004/01/24 05:00 [medline]
PHST- 2003/12/04 05:00 [entrez]
AID - 10.1002/ijc.11520 [doi]
PST - ppublish
SO  - Int J Cancer. 2004 Jan 20;108(3):367-73. doi: 10.1002/ijc.11520.