Document Detail

Effects of 1,25-dihydroxyvitamin D3 on cell-cycle kinetics of T 47D human breast cancer cells.
MedLine Citation:
PMID:  2925799     Owner:  NLM     Status:  MEDLINE    
The replication of several human and animal cancer cell lines is regulated in vitro and in vivo by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], the hormonally active form of vitamin D3. We have examined the effects of concentrations of 1,25-(OH)2D3, which inhibit cellular replication, on the cell-cycle kinetics of a 1,25-(OH)2D3-responsive human breast cancer cell line, T 47D. After 6 or 7 days of treatment, a time period representing approximately five cell population doublings of control cultures, concentrations of 1,25-(OH)2D3 in the range 10(-9) M to 10(-6) M caused a time- and concentration-dependent decrease in cell numbers. Treatment of cells growing in charcoal-treated fetal calf serum with 10(-8) M 1,25-(OH)2D3 for 6 days reduced cell numbers to 49% +/- 9% (n = 9) of control, and this was associated with a marked increase in the proportion of cells in the G2 + M phase of the cell cycle from 9.7% +/- 0.5% (n = 11) to 19.6% +/- 2.3% (n = 9), significant by paired analysis (P less than 0.002). At higher concentrations of 1,25-(OH)2D3 (10(-7)-10(-6) M), there was a concentration-dependent decline in S phase and increases in both G0/G1 and G2 + M phase cells. Detailed analysis of the temporal changes in cell-cycle phase distribution following treatment with 2.5 X 10(-8) and 10(-7) M 1,25-(OH)2D3 showed an initial accumulation of cells in G0/G1 and depletion of S phase cells during the first 24 hr of treatment. This decline in S phase cells was not accompanied by a decline in % G2 + M indicating a transition delay in G2 or mitosis. At the lower dose these changes returned to control values at 48 hr and at later times were associated with a slight but consistent decline in G0/G1 phase and an increase in G2 + M. In contrast cells treated with 10(-7) M 1,25-(OH)2D3 had significantly elevated % G0/G1 cells at days 2 and 3, consistent with a transition delay through G1 phase. This was confirmed in stathmokinetic experiments which demonstrated an approximate sevenfold decrease in the rate of exit of cells from G0/G1 following 4 days of exposure to 10(-7) M 1,25-(OH)2D3. This accumulation of cells in G0/G1 was accompanied by a fall in % S phase cells.(ABSTRACT TRUNCATED AT 400 WORDS)
J A Eisman; R L Sutherland; M L McMenemy; J C Fragonas; E A Musgrove; G Y Pang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  138     ISSN:  0021-9541     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  1989 Mar 
Date Detail:
Created Date:  1989-04-25     Completed Date:  1989-04-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  611-6     Citation Subset:  IM    
Garvan Institute of Medical Research, St Vincent's Hospital, Sydney, N.S.W., Australia.
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MeSH Terms
Breast Neoplasms / pathology*
Calcitriol / pharmacology*
Cell Cycle / drug effects*
DNA, Neoplasm / biosynthesis
Dose-Response Relationship, Drug
Tamoxifen / pharmacology
Time Factors
Tumor Cells, Cultured
Reg. No./Substance:
0/DNA, Neoplasm; 10540-29-1/Tamoxifen; 32222-06-3/Calcitriol

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