Effects of 1,25‐dihydroxyvitamin D3 on cell‐cycle kinetics of T 47D human breast cancer cells

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 > 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 Go/G1 and G2 + M phase cells.

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