B. Vandewalle et al., VITAMIN-D-3 DERIVATIVES AND BREAST-TUMOR CELL-GROWTH - EFFECT ON INTRACELLULAR CALCIUM AND APOPTOSIS, International journal of cancer, 61(6), 1995, pp. 806-811
Vitamin-D-3 derivatives are now well-recognized growth inhibitors of n
umerous tumoral cells and in particular breast-cancer cells. However,
the mechanisms by which they operate are not well established. Among t
he wide range of physiological and biological functions of vitamin-D-3
derivatives, the best described include their action on calcium homeo
stasis. In this study, we sought to establish whether the effects of v
itamin-D-3 derivatives on breast-cancer cell growth may be in part rel
ated to intracellular calcium modulation and induction of apoptosis. T
o address these questions, we used, in addition to 1,25(OH)(2)D-3, the
active metabolite of vitamin D-3, a non-calcemic 1,25(OH)(2)D-3 deriv
ative: Ro 23-7553 [16-ene-23-yne-1,25(OH)(2)D-3], which in our hands w
as more potent than the parent compound in inhibiting breast-cancer ce
ll growth. We showed that the efficiency of both compounds in growth i
nhibition was higher in the estradiol-receptor-positive-breast-tumor M
CF-7 cells than in the estradiol-receptor-negative MDA-MB 231 cells. I
n MCF-7 cells in particular, important modifications of intracellular
calcium related to the emptying of intracellular pools were observed.
The depletion of Ca++ from intracellular stores was followed by the in
duction of apoptosis. Such a phenomenon was never observed in MDA-MB 2
31 cells. Our results suggest that the action of vitamin-D-3 derivativ
es on the depletion of calcium stores, which was more significant in M
CF-7 than in MDA-MB 231 cells, may induce apoptosis in the former cell
s and account for the high efficiency of vitamin-D-3 derivatives on gr
owth inhibition of MCF-7 breast-tumor (C) 1995 Wiley-Liss, Inc.